JAX
Mouse Strain Datasheet - 003383
129S-Nogtm1Amc/J
Also Known As: Noggin KO
These Nog knock-out, lacZ reporter mice exhibit multiple defects, including an open neural tube, skeletal abnormalities, shortened body axis, and a small vestigial tail.
Donating Investigator
Andrew P McMahon, University of Southern California
Genetic overview
| Genetic Background | Generation |
|---|---|
|
|
Nogtm1Amc
| Allele Type | Gene Symbol | Gene Name |
|---|---|---|
| Targeted (Null/Knockout, Reporter) | Nog | noggin |
Research Applications
- Developmental Biology Research
- Neurobiology Research
- Research Tools
Detailed Description
Homozygous mice are born but die shortly after birth, exhibiting multiple defects, including an open neural tube, skeletal abnormalities, shortened body axis, and a small vestigial tail. Analysis of early gene expression has shown that the loss of Nog expression in the floorplate, notochord, and roofplate results in a progressive failure of ventral development in the CNS and somites. Nog is also expressed in condensing cartilage in the limb and in the sclerotome of somites so its loss results in defects in cartilage patterning and skeletal morphogenesis. Heterozygous embryos show lacZ reporter expression in pattern consistent with the endogenous gene.
Development
A targeting vector containing neomycin resistance, herpes simplex virus thymidine kinase and lacZ genes was used to disrupt most of the Nog coding region and some 3' flanking sequence. The targeted allele consists of an in frame lacZ fusion to noggin's first 10 amino acids. The construct was electroporated into 129S1/Sv-derived CJ7 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6J blastocysts. The resulting chimeric animals were backcrossed to 129/Sv mice.
Expression Data
| Expressed Gene | lacZ, beta-galactosidase, E. coli |
|---|---|
| Site of Expression | Expression of the lacZ reporter is consistent with the expression pattern of the endogenous gene. |
Control Suggestions
- Wild-type from the colony
- 002448 129S1/SvImJ
Additional Information
Selected References
- McMahon JA; Takada S; Zimmerman LB; Fan CM; Harland RM; McMahon AP. 1998. Noggin-mediated antagonism of BMP signaling is required for growth and patterning of the neural tube and somite. Genes Dev 12(10):1438-52. PubMed: 9585504MGI: J:47724
Nogtm1Amc
Allele Symbol: Nogtm1Amc
| Allele Name | targeted mutation 1, Andrew P McMahon |
|---|---|
| Allele Type | Targeted (Null/Knockout, Reporter) |
| Allele Synonym(s) | Nog-; Nog9E; NogginlacZ; noggin- |
| Gene Symbol and Name | Nog, noggin |
| Gene Synonym(s) | SYM1; SYNS1; SYNS1A |
| Expressed Gene | lacZ, beta-galactosidase, E. coli |
| Site of Expression | Expression of the lacZ reporter is consistent with the expression pattern of the endogenous gene. |
| Strain of Origin | 129S1/Sv-Oca2<+> Tyr<+> Kitl<+> |
| Chromosome | 11 |
| Molecular Note | Gene targeting generated a null allele by fusing the first 10 amino acids of coding sequence in-frame to the lacZ gene. The remainder of the coding sequence and some of the 3' flanking sequence of the gene were deleted. Ectopic expression of the resulting transcript was noted. |
| Mutations Made By | Andrew McMahon, University of Southern California |
Disease Terms
Research Areas By Genotype
This mouse can be used to support research in many areas including:
- Developmental Biology Research
- Neurodevelopmental Defects
- Perinatal Lethality
- Homozygous
- Neurobiology Research
- Neurodevelopmental Defects
- Research Tools
- lacZ Expression
- Developmental Biology Research
Genotype: Nogtm1Amc related
- Developmental Biology Research
- Embryonic Lethality (Homozygous)
- Neural Tube Defects
- Neurodevelopmental Defects
- Postnatal Lethality
- Skeletal Defects
- Neurobiology Research
- Neural Tube Defects
- Neurodevelopmental Defects
Mammalian Phenotype Terms by Genotype
Genotype: Nogtm1Amc/Nogtm1Amc
involves: 129S1/Sv
mortality/aging
- perinatal lethality, complete penetrance
nervous system phenotype
- abnormal neural plate morphology
- neural plate shows furrows and kinks in open cranial portion and closed spinal portion (MGI Ref ID J:110617)
- abnormal neural tube closure
- abnormal neural tube morphology
- all homozygous embryos from heterozygous crosses where females injected with folate or myo-inositol still show neural tube defects (NTDs) (MGI Ref ID J:110617)
- at E10 and E11, development of the spinal cord shows severe disruption, with regions of the neural tube appearing ruptured (MGI Ref ID J:110617)
- between the limbs, flattened neural mass beneath edematous tissue replaces neural tube (MGI Ref ID J:110617)
- defective neurulation is detected at E9.0 (MGI Ref ID J:110617)
- neural tube at level of forelimbs is mildly affected (MGI Ref ID J:110617)
- abnormal spinal cord morphology
- by E14, spinal cord is splayed open and dysmorphic in lumbar region, but remains closed at forelimb level (MGI Ref ID J:110617)
- exencephaly
- Background Sensitivity - exencephaly is completely penetrant on 129/Sv background, but is almost never observed on C57BL/6 background and is variably observed on mixed or outbred backgrounds (MGI Ref ID J:110617)
- in mutants where the frontal, parietal and interparietal bones are absent, the brain is exposed at birth (MGI Ref ID J:74136)
- large convoluted mass of brain tissue protrudes from head (MGI Ref ID J:110617)
- midbrain and hindbrain regions are directly exposed to extraembryonic environment (MGI Ref ID J:110617)
- incomplete rostral neuropore closure
- all but most rostral portion of neural tube remains splayed open with no surface ectoderm covering open neural tissue at E9.0 (MGI Ref ID J:110617)
- kinked neural tube
- observed in embryos at E8 or E9 (MGI Ref ID J:110617)
- open neural tube
- (MGI Ref ID J:74136)
- spina bifida occulta
- all homozygotes have spina bifida; caudal to forelimb, dorsal neural arches are absent (MGI Ref ID J:110617)
- stillborn pups, spina bifida is restricted to the lumbar region between forelimb and hindlimb (MGI Ref ID J:110617)
- vertebral arches of axial skeleton are split in two, but surface ectoderm remains intact (MGI Ref ID J:110617)
- wavy neural tube
- observed in embryos at E8 or E9 (MGI Ref ID J:110617)
skeleton phenotype
- abnormal axial skeleton morphology
- abnormal basicranium morphology
- fusion of presphenoid, basisphenoid, and basioccipital bones (MGI Ref ID J:74136)
- abnormal frontal bone morphology
- frontal bone is loose or absent (MGI Ref ID J:74136)
- abnormal interparietal bone morphology
- interparietal bone is loose or absent (MGI Ref ID J:74136)
- abnormal occipital bone morphology
- occipital condyles are loose, showing variability in the distance separating them (MGI Ref ID J:74136)
- abnormal parietal bone morphology
- parietal bone is loose or absent (MGI Ref ID J:74136)
- abnormal vertebral arch morphology
- vertebral arches of axial skeleton are split in two, but surface ectoderm remains intact (MGI Ref ID J:110617)
- absent vertebral arch
- caudal to forelimb, dorsal neural arches are absent (MGI Ref ID J:110617)
- spina bifida occulta
- all homozygotes have spina bifida; caudal to forelimb, dorsal neural arches are absent (MGI Ref ID J:110617)
- stillborn pups, spina bifida is restricted to the lumbar region between forelimb and hindlimb (MGI Ref ID J:110617)
- vertebral arches of axial skeleton are split in two, but surface ectoderm remains intact (MGI Ref ID J:110617)
limbs/digits/tail phenotype
- absent tail
- (MGI Ref ID J:74136)
- short limbs
- truncated limbs (MGI Ref ID J:74136)
respiratory system phenotype
- abnormal lung development
- blind-ended ectopic buds or diverticulum emerging near the junction of the main bronchi are present in 31% of embryos (MGI Ref ID J:83697)
- abnormal lung morphology
- at E15.5 all mice have abnormal lungs with malformed and truncated lobes (MGI Ref ID J:83697)
- abnormal right lung morphology
- fusions of the right lobes are seen in 78% of embryos (MGI Ref ID J:83697)
craniofacial phenotype
- abnormal basicranium morphology
- fusion of presphenoid, basisphenoid, and basioccipital bones (MGI Ref ID J:74136)
- abnormal frontal bone morphology
- frontal bone is loose or absent (MGI Ref ID J:74136)
- abnormal interparietal bone morphology
- interparietal bone is loose or absent (MGI Ref ID J:74136)
- abnormal occipital bone morphology
- occipital condyles are loose, showing variability in the distance separating them (MGI Ref ID J:74136)
- abnormal parietal bone morphology
- parietal bone is loose or absent (MGI Ref ID J:74136)
cellular phenotype
- increased apoptosis
- (MGI Ref ID J:110617)
embryo phenotype
- abnormal neural plate morphology
- neural plate shows furrows and kinks in open cranial portion and closed spinal portion (MGI Ref ID J:110617)
- abnormal neural tube closure
- abnormal neural tube morphology
- all homozygous embryos from heterozygous crosses where females injected with folate or myo-inositol still show neural tube defects (NTDs) (MGI Ref ID J:110617)
- at E10 and E11, development of the spinal cord shows severe disruption, with regions of the neural tube appearing ruptured (MGI Ref ID J:110617)
- between the limbs, flattened neural mass beneath edematous tissue replaces neural tube (MGI Ref ID J:110617)
- defective neurulation is detected at E9.0 (MGI Ref ID J:110617)
- neural tube at level of forelimbs is mildly affected (MGI Ref ID J:110617)
- abnormal somite development
- somite differentiation is disrupted in lumbar region of embryos at E9-10 (MGI Ref ID J:110617)
- incomplete rostral neuropore closure
- all but most rostral portion of neural tube remains splayed open with no surface ectoderm covering open neural tissue at E9.0 (MGI Ref ID J:110617)
- kinked neural tube
- observed in embryos at E8 or E9 (MGI Ref ID J:110617)
- open neural tube
- (MGI Ref ID J:74136)
- spina bifida occulta
- all homozygotes have spina bifida; caudal to forelimb, dorsal neural arches are absent (MGI Ref ID J:110617)
- stillborn pups, spina bifida is restricted to the lumbar region between forelimb and hindlimb (MGI Ref ID J:110617)
- vertebral arches of axial skeleton are split in two, but surface ectoderm remains intact (MGI Ref ID J:110617)
- wavy neural tube
- observed in embryos at E8 or E9 (MGI Ref ID J:110617)
The following phenotype information is associated with a similar, but not exact match to this JAX® Mice strain
Genotype: Nogtm1Amc/Nog+
involves: 129S1/Sv * CD-1
skeleton phenotype
- abnormal axial skeleton morphology
- (MGI Ref ID J:108573)
- abnormal rib morphology
- (MGI Ref ID J:108573)
- fused synovial joints
- kyphosis
- Background Sensitivity - in 30% of mice (MGI Ref ID J:108573)
- small thoracic cage
- reduced rib cage due to malformed ribs (MGI Ref ID J:108573)
limbs/digits/tail phenotype
- kinked tail
- in embryos at E14.5 (MGI Ref ID J:108573)
Genotype: Nogtm1Amc/Nog+
D1.129S1-Nogtm1Amc
skeleton phenotype
- abnormal middle ear ossicle morphology
- bone bridges are not observed in unaffected or mildly affected ears (MGI Ref ID J:132023)
- fragment is located where stapedius muscle is connected to temporal bone in wild-type ears (MGI Ref ID J:132023)
- mice displaying hearing threshold shifts of >10 dB at two or more frequencies have an extra bone fragment between posterior crus of stapes and posterior wall of tympanium (MGI Ref ID J:132023)
- mice with threshold shifts >10 dB show rigid extra bone bridge in middle ear cavity; mice with less severe or unaffected threshold changes have bone fragments consisting of two unfused pieces that are found in the same location as in significantly affected earsd ears (MGI Ref ID J:132023)
- no extra bone fragment associated with the malleus or incus was observed (MGI Ref ID J:132023)
- abnormal rib morphology
- (MGI Ref ID J:108573)
- abnormal stapes morphology
- in mice aged E15.5 to P4 the ectopic bone is located between the stapes and styloid process, likely due to failure of the stapes and styloid process to separate normally (MGI Ref ID J:132023)
- abnormal styloid process morphology
- in mice aged E15.5 to P4 the ectopic bone is located between the stapes and styloid process, likely due to failure of the stapes and styloid process to separate normally (MGI Ref ID J:132023)
- fused synovial joints
- small thoracic cage
- reduced rib cage due to malformed ribs (MGI Ref ID J:108573)
limbs/digits/tail phenotype
- kinked tail
- in embryos at E14.5 (MGI Ref ID J:108573)
craniofacial phenotype
- abnormal middle ear ossicle morphology
- bone bridges are not observed in unaffected or mildly affected ears (MGI Ref ID J:132023)
- fragment is located where stapedius muscle is connected to temporal bone in wild-type ears (MGI Ref ID J:132023)
- mice displaying hearing threshold shifts of >10 dB at two or more frequencies have an extra bone fragment between posterior crus of stapes and posterior wall of tympanium (MGI Ref ID J:132023)
- mice with threshold shifts >10 dB show rigid extra bone bridge in middle ear cavity; mice with less severe or unaffected threshold changes have bone fragments consisting of two unfused pieces that are found in the same location as in significantly affected earsd ears (MGI Ref ID J:132023)
- no extra bone fragment associated with the malleus or incus was observed (MGI Ref ID J:132023)
- abnormal stapes morphology
- in mice aged E15.5 to P4 the ectopic bone is located between the stapes and styloid process, likely due to failure of the stapes and styloid process to separate normally (MGI Ref ID J:132023)
- abnormal styloid process morphology
- in mice aged E15.5 to P4 the ectopic bone is located between the stapes and styloid process, likely due to failure of the stapes and styloid process to separate normally (MGI Ref ID J:132023)
hearing/vestibular/ear phenotype
- abnormal middle ear morphology
- (MGI Ref ID J:132023)
- abnormal middle ear ossicle morphology
- bone bridges are not observed in unaffected or mildly affected ears (MGI Ref ID J:132023)
- fragment is located where stapedius muscle is connected to temporal bone in wild-type ears (MGI Ref ID J:132023)
- mice displaying hearing threshold shifts of >10 dB at two or more frequencies have an extra bone fragment between posterior crus of stapes and posterior wall of tympanium (MGI Ref ID J:132023)
- mice with threshold shifts >10 dB show rigid extra bone bridge in middle ear cavity; mice with less severe or unaffected threshold changes have bone fragments consisting of two unfused pieces that are found in the same location as in significantly affected earsd ears (MGI Ref ID J:132023)
- no extra bone fragment associated with the malleus or incus was observed (MGI Ref ID J:132023)
- abnormal stapes morphology
- in mice aged E15.5 to P4 the ectopic bone is located between the stapes and styloid process, likely due to failure of the stapes and styloid process to separate normally (MGI Ref ID J:132023)
- conductive hearing loss
- (MGI Ref ID J:132023)
- impaired hearing
- remaining mice do not show significant threshold differences from wild-type (MGI Ref ID J:132023)
- increased or absent threshold for auditory brainstem response
- Background Sensitivity - many animals on congenic background show increased ABR thresholds relative to wild-type mice; these animals hearing threshold shifts >10dB at 2 or more different frequencies in one or both ears (MGI Ref ID J:132023)
Genotype: Nogtm1Amc/Nog+
B6.129S1-Nogtm1Amc
skeleton phenotype
- abnormal rib morphology
- (MGI Ref ID J:108573)
- fused synovial joints
- small thoracic cage
- reduced rib cage due to malformed ribs (MGI Ref ID J:108573)
limbs/digits/tail phenotype
- kinked tail
- in embryos at E14.5 (MGI Ref ID J:108573)
Genotype: Nogtm1Amc/Nog+
involves: C57BL/6J * FVB
hearing/vestibular/ear phenotype
- hearing/vestibular/ear phenotype
- Background Sensitivity - no hearing impairment is observed in heterozygous mice on a mixed background (MGI Ref ID J:132023)
Genotype: Nogtm1Amc/Nog+
involves: 129S1/Sv * C57BL/6J * ICR
endocrine/exocrine gland phenotype
- small prostate gland ventral lobe
- at P35 ventral prostate lobe weight is significantly lower than in wild-type males (MGI Ref ID J:130204)
- however, no differences in weights of dorsolateral prostate or coagulating gland weights or in numbers of main ducts, branch points or tips are observed relative to wild-type prostate lobes (MGI Ref ID J:130204)
reproductive system phenotype
- small prostate gland ventral lobe
- at P35 ventral prostate lobe weight is significantly lower than in wild-type males (MGI Ref ID J:130204)
- however, no differences in weights of dorsolateral prostate or coagulating gland weights or in numbers of main ducts, branch points or tips are observed relative to wild-type prostate lobes (MGI Ref ID J:130204)
Genotype: Nogtm1Amc/Nogtm1Amc
either: (involves: 129S1/Sv * CD-1) or (involves: 129S1/Sv * 129X1/SvJ * C57BL/6)
endocrine/exocrine gland phenotype
- abnormal Rathke's pouch apoptosis
- domain of apoptosis normally observed on ventral side of pouch is absent in mutants at E10.5 and E11.5; apoptotic cells are not observed in mutants that do not achieve separation of Rathke's pouch (MGI Ref ID J:121318)
- abnormal Rathke's pouch development
- commonly, Rathke's pouch is elongated and extend more rostrally than in wild-type; eventually cartilage plate surrounds mutant pituitary tissue (MGI Ref ID J:121318)
- severely malformed at E10.5 with multiple invaginations within oral ectoderm; some embryos show duplication of Rathke's pouch with the two invaginations widely spaced or arising adjacent to each other (MGI Ref ID J:121318)
- abnormal pituitary gland development
- Rathke's pouch and anterior lobe development are severely affected (MGI Ref ID J:121318)
- secondary pituitary tissue is found in some embryos examined at E11.5-14.5 with percentage of affected embryos decreasing when examined at later time point (E15.5-18.5) (MGI Ref ID J:121318)
- some cell specification appears to occur in pituitary tissue (MGI Ref ID J:121318)
- abnormal pituitary gland physiology
- all normal pituitary hormones are detected in primary anterior lobe of mutants but levels are variable, dependent on number of terminally differentiated cells (MGI Ref ID J:121318)
- absent Rathke's pouch
- about 14% of embryos don't appear to have a Rathke's pouch at E12.5 (MGI Ref ID J:121318)
- absent adenohypophysis
- in embryos with elongated, rostrally-positioned Rathke's pouch, developed anterior lobe is absent (MGI Ref ID J:121318)
- absent pituitary gland
- in some embryos an identifiable pituitary is not found at E12.5-16.5; normal position of pituitary is filled with mesenchyme in these embryos (MGI Ref ID J:121318)
- absent pituitary infundibular stalk
- morphologically distinct infundibulum is absent in most embryos examined between E12.5 and 16.5 (MGI Ref ID J:121318)
nervous system phenotype
- abnormal Rathke's pouch apoptosis
- domain of apoptosis normally observed on ventral side of pouch is absent in mutants at E10.5 and E11.5; apoptotic cells are not observed in mutants that do not achieve separation of Rathke's pouch (MGI Ref ID J:121318)
- abnormal Rathke's pouch development
- commonly, Rathke's pouch is elongated and extend more rostrally than in wild-type; eventually cartilage plate surrounds mutant pituitary tissue (MGI Ref ID J:121318)
- severely malformed at E10.5 with multiple invaginations within oral ectoderm; some embryos show duplication of Rathke's pouch with the two invaginations widely spaced or arising adjacent to each other (MGI Ref ID J:121318)
- abnormal diencephalon morphology
- a large domain of cell death is observed in ventral diencephalon of mutants but not in wild-type (MGI Ref ID J:121318)
- thickening of neuroepithelium in ventral diencephalon rostral to Rathke's pouch is decreased or absent in contrast to wild-type embryos (MGI Ref ID J:121318)
- ventral diencephalon displays abnormalities (MGI Ref ID J:121318)
- abnormal neural tube morphology
- severe neural tube defect is occasionally observed (MGI Ref ID J:121318)
- abnormal pituitary gland development
- Rathke's pouch and anterior lobe development are severely affected (MGI Ref ID J:121318)
- secondary pituitary tissue is found in some embryos examined at E11.5-14.5 with percentage of affected embryos decreasing when examined at later time point (E15.5-18.5) (MGI Ref ID J:121318)
- some cell specification appears to occur in pituitary tissue (MGI Ref ID J:121318)
- abnormal pituitary gland physiology
- all normal pituitary hormones are detected in primary anterior lobe of mutants but levels are variable, dependent on number of terminally differentiated cells (MGI Ref ID J:121318)
- absent Rathke's pouch
- about 14% of embryos don't appear to have a Rathke's pouch at E12.5 (MGI Ref ID J:121318)
- absent adenohypophysis
- in embryos with elongated, rostrally-positioned Rathke's pouch, developed anterior lobe is absent (MGI Ref ID J:121318)
- absent pituitary gland
- in some embryos an identifiable pituitary is not found at E12.5-16.5; normal position of pituitary is filled with mesenchyme in these embryos (MGI Ref ID J:121318)
- absent pituitary infundibular stalk
- morphologically distinct infundibulum is absent in most embryos examined between E12.5 and 16.5 (MGI Ref ID J:121318)
embryo phenotype
- abnormal neural tube morphology
- severe neural tube defect is occasionally observed (MGI Ref ID J:121318)
growth/size/body region phenotype
- abnormal head morphology
- with severe neural tube defect gross head morphology is altered, being split down anterior midline at E15.5 (MGI Ref ID J:121318)
Genotype: Nogtm1Amc/Nogtm1Amc
involves: 129S1/Sv * C57BL/6J * FVB/N
hearing/vestibular/ear phenotype
- abnormal cochlea morphology
- length of cochlea is shorter by 35% compared to heterozygous controls at E18.5 (MGI Ref ID J:156945)
- decreased cochlear coiling
- cochleae of controls show 1.75 turns compared to only 1 turn in mutants (MGI Ref ID J:156945)
- increased cochlear inner hair cell number
- cochleae have occasional extra inner hair cells (IHCs) at the base of the cochlea, and two rows of IHCs in the middle and apical turns instead of a single row as in controls (MGI Ref ID J:156945)
- increase in IHCs is observed in any given region but is more pronounced in apical and middle turns (MGI Ref ID J:156945)
- total estimated IHC number based on entire length of cochlear duct is increased by 11% (MGI Ref ID J:156945)
- increased cochlear outer hair cell number
- an extra row of outer hair cells (OHCs) is observed in the apical and middle turns of the cochleae; numbers increase significantly throughout each turn (MGI Ref ID J:156945)
- however, total estimated OHC number based on entire length of cochlear duct is decreased by 24% compared to heterozygous controls (MGI Ref ID J:156945)
nervous system phenotype
- increased cochlear inner hair cell number
- cochleae have occasional extra inner hair cells (IHCs) at the base of the cochlea, and two rows of IHCs in the middle and apical turns instead of a single row as in controls (MGI Ref ID J:156945)
- increase in IHCs is observed in any given region but is more pronounced in apical and middle turns (MGI Ref ID J:156945)
- total estimated IHC number based on entire length of cochlear duct is increased by 11% (MGI Ref ID J:156945)
- increased cochlear outer hair cell number
- an extra row of outer hair cells (OHCs) is observed in the apical and middle turns of the cochleae; numbers increase significantly throughout each turn (MGI Ref ID J:156945)
- however, total estimated OHC number based on entire length of cochlear duct is decreased by 24% compared to heterozygous controls (MGI Ref ID J:156945)
Genotype: Nogtm1Amc/Nogtm1Amc
either: (involves: 129S1/Sv * C57BL/6) or (involves: 129S1/Sv * CD-1 * ICR)
embryo phenotype
- abnormal neural tube morphology
- (MGI Ref ID J:118341)
- abnormal notochord morphology
- abnormal at E8.5 and E9, indicating delayed detachment from dorsal foregut endoderm; appears hypertrophic compared to wild-type at E9 (MGI Ref ID J:118341)
- at E9.5, notochord has lateral branches close to or tethered to dorsal foregut in contrast to wild-type notochord (MGI Ref ID J:118341)
- increased apoptotic cell numbers are seen at E9.5-E9.75 (MGI Ref ID J:118341)
- no clear boundary between notochord and endoderm is detected at E8.5 (MGI Ref ID J:118341)
- non-notochordal cells are observed within the notochord at E9.0 (MGI Ref ID J:118341)
- incomplete rostral neuropore closure
- at E11.5 embryos show open brain phenotype (MGI Ref ID J:118341)
- open neural tube
- at E11.5 caudal neural tube is open (MGI Ref ID J:118341)
digestive/alimentary phenotype
- abnormal esophagus development
- at E10.5-11.5 most mutants display Type C esophageal atresia/tracheoesophageal fistula (EA/TEF); some embryos show milder phenotype indicative of esophageal stenosis (MGI Ref ID J:118341)
- abnormal foregut morphology
- esophageal atresia
- at E10.5-11.5, >80% of embryos display Type C esophageal atresia/tracheoesophageal fistula (EA/TEF) (MGI Ref ID J:118341)
- esophagus stenosis
- severe narrowing of the esophagus is seen by E9.5 (MGI Ref ID J:118341)
- tracheoesophageal fistula
- at E10.5-11.5, >80% of embryos display Type C esophageal atresia/tracheoesophageal fistula (EA/TEF) with the upper esophagus ending in a blind pouch and the lower esophagus connects to the trachea via a fistula (MGI Ref ID J:118341)
nervous system phenotype
- abnormal neural tube morphology
- (MGI Ref ID J:118341)
- incomplete rostral neuropore closure
- at E11.5 embryos show open brain phenotype (MGI Ref ID J:118341)
- open neural tube
- at E11.5 caudal neural tube is open (MGI Ref ID J:118341)
respiratory system phenotype
- tracheoesophageal fistula
- at E10.5-11.5, >80% of embryos display Type C esophageal atresia/tracheoesophageal fistula (EA/TEF) with the upper esophagus ending in a blind pouch and the lower esophagus connects to the trachea via a fistula (MGI Ref ID J:118341)
Genotype: Nogtm1Amc/Nogtm1Amc
involves: 129S1/Sv * C57BL/6J * ICR
embryo phenotype
- abnormal primitive urogenital sinus morphology
- UGS is smaller at E17 in males (MGI Ref ID J:130204)
- abnormal septation of the cloaca
- at E14 ventral mesenchymal cell density of UGS is reduced relative to E14 wild-type embryos indicating defective development of the ventral mesenchyme pad; this reduced cell density occurs along with decreased epithelial cell proliferation in the ventral UGSUGS (MGI Ref ID J:130204)
- at E17 males have a fistulous connection between hindgut and dorsal surface of UGS; females show similar defects at E17 (MGI Ref ID J:130204)
- at P1 this is observed as reduction in ventral mesenchyme pad thickness and density (MGI Ref ID J:130204)
- incomplete separation of the hindgut from the urogenital sinus (UGS) is observed in some embryos (MGI Ref ID J:130204)
reproductive system phenotype
- abnormal male reproductive system morphology
- dorsal ridges are absent or reduced in size; dorsal sulcus is missing and ejaculatory duct connection is exposed (MGI Ref ID J:130204)
- abnormal prostate gland development
- abnormal prostate gland morphology
- dorsal and lateral buds are reduced in number but a degree of ductal branching is observed in all embryos (MGI Ref ID J:130204)
- absent bulbourethral gland
- some males show agenesis of the bulbourethral gland (MGI Ref ID J:130204)
- cryptorchism
- varying degrees of cryptorchism ranging from high intra-abdominal position to complete descent (MGI Ref ID J:130204)
renal/urinary system phenotype
- abnormal urethra morphology
- angle between bladder neck and urethra in urogenital sinus (UGS) is much larger than the approximate 90 degrees seen in wild-type embryos (MGI Ref ID J:130204)
- some males exhibit agenesis of the membranous (pelvic) urethra while others develop a preursor urethral epithelial tube (MGI Ref ID J:130204)
- abnormal urinary system development
- (MGI Ref ID J:130204)
- pelvic kidney
- occasionally an ectopic kidney is observed in the pelvic cavity (MGI Ref ID J:130204)
digestive/alimentary phenotype
- anal atresia
- fistulous connection between hindgut and dorsal UGS surface is typically associated with anal atresia in males and females (MGI Ref ID J:130204)
endocrine/exocrine gland phenotype
- abnormal prostate gland development
- abnormal prostate gland morphology
- dorsal and lateral buds are reduced in number but a degree of ductal branching is observed in all embryos (MGI Ref ID J:130204)
- absent bulbourethral gland
- some males show agenesis of the bulbourethral gland (MGI Ref ID J:130204)
- cryptorchism
- varying degrees of cryptorchism ranging from high intra-abdominal position to complete descent (MGI Ref ID J:130204)
limbs/digits/tail phenotype
- absent tail
- some embryos exhibit agenesis of the tail (MGI Ref ID J:130204)
Genotype: Nogtm1Amc/Nogtm1Amc
B6.129S1-Nogtm1Amc
mortality/aging
- lethality throughout fetal growth and development, complete penetrance
- Background Sensitivity - embryo death before E14.5 on a B6.129S1 background (MGI Ref ID J:108573)
embryo phenotype
- small limb buds
- Background Sensitivity - reduction in limb buds is seen on the C57BL/6 background but not so much on a CD-1 background (MGI Ref ID J:108573)
hearing/vestibular/ear phenotype
- abnormal incus morphology
- at E17.5 incus is malformed (MGI Ref ID J:132023)
- abnormal malleus morphology
- at E17.5 malleus is malformed (MGI Ref ID J:132023)
- fusion of middle ear ossicles
- at E17.5 embryos display overgrown and fused ossicles not identifiable as discrete entities (MGI Ref ID J:132023)
craniofacial phenotype
- abnormal incus morphology
- at E17.5 incus is malformed (MGI Ref ID J:132023)
- abnormal malleus morphology
- at E17.5 malleus is malformed (MGI Ref ID J:132023)
- fusion of middle ear ossicles
- at E17.5 embryos display overgrown and fused ossicles not identifiable as discrete entities (MGI Ref ID J:132023)
limbs/digits/tail phenotype
- small limb buds
- Background Sensitivity - reduction in limb buds is seen on the C57BL/6 background but not so much on a CD-1 background (MGI Ref ID J:108573)
skeleton phenotype
- abnormal incus morphology
- at E17.5 incus is malformed (MGI Ref ID J:132023)
- abnormal malleus morphology
- at E17.5 malleus is malformed (MGI Ref ID J:132023)
- fusion of middle ear ossicles
- at E17.5 embryos display overgrown and fused ossicles not identifiable as discrete entities (MGI Ref ID J:132023)
Genotype: Nogtm1Amc/Nogtm1Amc
D1.129S1-Nogtm1Amc
mortality/aging
- perinatal lethality
- (MGI Ref ID J:108573)
nervous system phenotype
- exencephaly
- 25% penetrance, lower than on a CD-1 background (MGI Ref ID J:108573)
Genotype: Nogtm1Amc/Nogtm1Amc
involves: 129S1/Sv * CD-1
mortality/aging
- perinatal lethality
- (MGI Ref ID J:108573)
integument phenotype
- abnormal hair follicle development
- rudimentary hair follicles at E18.5 (MGI Ref ID J:108573)
skeleton phenotype
- abnormal bone mineralization
- highly variable throughout the skeleton but characteristic for each region (MGI Ref ID J:108573)
- fused synovial joints
- elbow fusion (MGI Ref ID J:108573)
limbs/digits/tail phenotype
- abnormal limb bud morphology
- Background Sensitivity - limb bud phenotype is much less pronounced, such that they almost appear normal, in the CD-1 background compared to the C57BL/6 background (MGI Ref ID J:108573)
- abnormal limb morphology
- newbrons exhibit stubby limbs (MGI Ref ID J:108573)
- vestigial tail
- degeneration of the tail structure is seen at E12.5 (MGI Ref ID J:108573)
homeostasis/metabolism phenotype
- edema
- observed at E14.5 (MGI Ref ID J:108573)
muscle phenotype
- abnormal muscle fiber morphology
- myofibers in loose structures rather than tightly packed (MGI Ref ID J:108573)
- abnormal muscle morphology
- reduced muscle tissue in newborns (MGI Ref ID J:108573)
cardiovascular system phenotype
- hematoma
- a large hematoma is often seen in the degenerating tail at E12.5 and by E14.5, hematomas in other parts of the body are seen (MGI Ref ID J:108573)
nervous system phenotype
- exencephaly
- Background Sensitivity - 60% penetrance, higher than on a DBA/1 background (MGI Ref ID J:108573)
growth/size/body region phenotype
- decreased fetal size
- shorter along the rostral-caudal axis (MGI Ref ID J:108573)
embryo phenotype
- abnormal limb bud morphology
- Background Sensitivity - limb bud phenotype is much less pronounced, such that they almost appear normal, in the CD-1 background compared to the C57BL/6 background (MGI Ref ID J:108573)
Genotype: Nogtm1Amc/Nogtm1Amc
either: 129/Sv or (involves: 129S1/Sv * C57BL/6J)
mortality/aging
- perinatal lethality, complete penetrance
- (MGI Ref ID J:47724)
nervous system phenotype
- abnormal neural tube morphology
- reduced in size (MGI Ref ID J:47724)
- abnormal spinal cord morphology
- becomes kinked on both backgrounds (MGI Ref ID J:47724)
- incomplete rostral neuropore closure
- Background Sensitivity - neural folds flatten at the 8-9 somite stage on the 129/Sv background (MGI Ref ID J:47724)
- Background Sensitivity - on a 129/Sv background the brain fails to close between the diencephalons and myelencephalon, sometimes remaining open all the way to the caudal limit (MGI Ref ID J:47724)
- Background Sensitivity - on a mixed background the brain closes (MGI Ref ID J:47724)
embryo phenotype
- abnormal neural tube morphology
- reduced in size (MGI Ref ID J:47724)
- abnormal notochord morphology
- occasional side branching and buckling at E10.5 (MGI Ref ID J:47724)
- abnormal rostral-caudal patterning of the somites
- abnormalities become increasingly severe in a caudal direction (MGI Ref ID J:47724)
- abnormal somite development
- (MGI Ref ID J:47724)
- decreased embryo size
- (MGI Ref ID J:47724)
- decreased somite size
- reduced (MGI Ref ID J:47724)
- incomplete rostral neuropore closure
- Background Sensitivity - neural folds flatten at the 8-9 somite stage on the 129/Sv background (MGI Ref ID J:47724)
- Background Sensitivity - on a 129/Sv background the brain fails to close between the diencephalons and myelencephalon, sometimes remaining open all the way to the caudal limit (MGI Ref ID J:47724)
- Background Sensitivity - on a mixed background the brain closes (MGI Ref ID J:47724)
skeleton phenotype
- abnormal axial skeleton morphology
- shortened axis between fore and hind limbs (MGI Ref ID J:47724)
vision/eye phenotype
- abnormal eye development
- perturbed (MGI Ref ID J:47724)
hearing/vestibular/ear phenotype
- abnormal ear development
- perturbed (MGI Ref ID J:47724)
limbs/digits/tail phenotype
- short limbs
- broad club shaped limbs (MGI Ref ID J:47724)
- vestigial tail
- reduced at E12.5, absent later (MGI Ref ID J:47724)
growth/size/body region phenotype
- decreased embryo size
- (MGI Ref ID J:47724)
integument phenotype
Genotype: Nogtm1Amc/Nogtm1Amc
involves: C57BL/6
mortality/aging
- perinatal lethality, complete penetrance
- mice all die perinatally (MGI Ref ID J:110617)
nervous system phenotype
- abnormal neural tube morphology
- all homozygotes display spinal neural tube defects (MGI Ref ID J:110617)
- exencephaly
- never observed on C57BL/6 inbred background (MGI Ref ID J:110617)
skeleton phenotype
- abnormal skeleton morphology
- all homozygotes display severe skeletal malformations (MGI Ref ID J:110617)
craniofacial phenotype
- abnormal craniofacial morphology
- some mutants show severe craniofacial truncations (MGI Ref ID J:110617)
- short face
- some mutants show mild facial truncations (MGI Ref ID J:110617)
embryo phenotype
- abnormal neural tube morphology
- all homozygotes display spinal neural tube defects (MGI Ref ID J:110617)
growth/size/body region phenotype
- short face
- some mutants show mild facial truncations (MGI Ref ID J:110617)
References
- McMahon JA; Takada S; Zimmerman LB; Fan CM; Harland RM; McMahon AP. 1998. Noggin-mediated antagonism of BMP signaling is required for growth and patterning of the neural tube and somite. Genes Dev 12(10):1438-52. PubMed: 9585504MGI: J:47724
Additional References
- Brunet LJ; McMahon JA; McMahon AP; Harland RM. 1998. Noggin, cartilage morphogenesis, and joint formation in the mammalian skeleton [see comments] Science 280(5368):1455-7. PubMed: 9603738MGI: J:48000
Additional - Nogtm1Amc related
- Anderson MJ; Schimmang T; Lewandoski M. 2016. An FGF3-BMP Signaling Axis Regulates Caudal Neural Tube Closure, Neural Crest Specification and Anterior-Posterior Axis Extension. PLoS Genet 12(5):e1006018. PubMed: 27144312MGI: J:232560
- Anderson RM; Lawrence AR; Stottmann RW; Bachiller D; Klingensmith J. 2002. Chordin and noggin promote organizing centers of forebrain development in the mouse. Development 129(21):4975-87. PubMed: 12397106MGI: J:79855
- Anderson RM; Stottmann RW; Choi M; Klingensmith J. 2006. Endogenous bone morphogenetic protein antagonists regulate mammalian neural crest generation and survival. Dev Dyn 235(9):2507-2520. PubMed: 16894609MGI: J:111609
- Bachiller D; Klingensmith J; Kemp C; Belo JA; Anderson RM; May SR; McMahon JA; McMahon AP; Harland RM; Rossant J; De Robertis EM. 2000. The organizer factors Chordin and Noggin are required for mouse forebrain development. Nature 403(6770):658-61. PubMed: 10688202MGI: J:60303
- Bok J; Brunet LJ; Howard O; Burton Q; Wu DK. 2007. Role of hindbrain in inner ear morphogenesis: Analysis of Noggin knockout mice. Dev Biol 311(1):69-78. PubMed: 17900554MGI: J:126342
- Borges AC; Marques S; Belo JA. 2001. The BMP antagonists cerberus-like and noggin do not interact during mouse forebrain development. Int J Dev Biol 45(2):441-4. PubMed: 11330864MGI: J:74136
- Botchkarev VA; Botchkareva NV; Nakamura M; Huber O; Funa K; Lauster R; Paus R; Gilchrest BA. 2001. Noggin is required for induction of the hair follicle growth phase in postnatal skin. FASEB J 15(12):2205-14. PubMed: 11641247MGI: J:71952
- Botchkarev VA; Botchkareva NV; Roth W; Nakamura M; Chen LH; Herzog W; Lindner G; McMahon JA; Peters C; Lauster R; McMahon AP; Paus R. 1999. Noggin is a mesenchymally derived stimulator of hair-follicle induction. Nat Cell Biol 1(3):158-64. PubMed: 10559902MGI: J:59676
- Brunet LJ; McMahon JA; McMahon AP; Harland RM. 1998. Noggin, cartilage morphogenesis, and joint formation in the mammalian skeleton [see comments] Science 280(5368):1455-7. PubMed: 9603738MGI: J:48000
- Canalis E; Brunet LJ; Parker K; Zanotti S. 2012. Conditional inactivation of noggin in the postnatal skeleton causes osteopenia. Endocrinology 153(4):1616-26. PubMed: 22334719MGI: J:183794
- Choi M; Stottmann RW; Yang YP; Meyers EN; Klingensmith J. 2007. The bone morphogenetic protein antagonist noggin regulates mammalian cardiac morphogenesis. Circ Res 100(2):220-8. PubMed: 17218603MGI: J:133691
- Cook C; Vezina CM; Allgeier SH; Shaw A; Yu M; Peterson RE; Bushman W. 2007. Noggin is required for normal lobe patterning and ductal budding in the mouse prostate. Dev Biol 312(1):217-30. PubMed: 18028901MGI: J:130204
- Davis SW; Camper SA. 2007. Noggin regulates Bmp4 activity during pituitary induction. Dev Biol 305(1):145-60. PubMed: 17359964MGI: J:121318
- Dionne MS; Brunet LJ; Eimon PM; Harland RM. 2002. Noggin is required for correct guidance of dorsal root ganglion axons. Dev Biol 251(2):283-93. PubMed: 12435358MGI: J:111207
- Dionne MS; Skarnes WC; Harland RM. 2001. Mutation and analysis of Dan, the founding member of the Dan family of transforming growth factor beta antagonists. Mol Cell Biol 21(2):636-43. PubMed: 11134349MGI: J:67351
- Fausett SR; Brunet LJ; Klingensmith J. 2014. BMP antagonism by Noggin is required in presumptive notochord cells for mammalian foregut morphogenesis. Dev Biol 391(1):111-24. PubMed: 24631216MGI: J:213659
- Forni PE; Bharti K; Flannery EM; Shimogori T; Wray S. 2013. The indirect role of fibroblast growth factor-8 in defining neurogenic niches of the olfactory/GnRH systems. J Neurosci 33(50):19620-34. PubMed: 24336726MGI: J:204657
- Guo W; Zhang L; Christopher DM; Teng ZQ; Fausett SR; Liu C; George OL; Klingensmith J; Jin P; Zhao X. 2011. RNA-binding protein FXR2 regulates adult hippocampal neurogenesis by reducing Noggin expression. Neuron 70(5):924-38. PubMed: 21658585MGI: J:174968
- He F; Xiong W; Wang Y; Matsui M; Yu X; Chai Y; Klingensmith J; Chen Y. 2010. Modulation of BMP signaling by Noggin is required for the maintenance of palatal epithelial integrity during palatogenesis. Dev Biol 347(1):109-21. PubMed: 20727875MGI: J:165723
- He XC; Zhang J; Tong WG; Tawfik O; Ross J; Scoville DH; Tian Q; Zeng X; He X; Wiedemann LM; Mishina Y; Li L. 2004. BMP signaling inhibits intestinal stem cell self-renewal through suppression of Wnt-beta-catenin signaling. Nat Genet 36(10):1117-21. PubMed: 15378062MGI: J:93850
- Hwang CH; Guo D; Harris MA; Howard O; Mishina Y; Gan L; Harris SE; Wu DK. 2010. Role of bone morphogenetic proteins on cochlear hair cell formation: analyses of Noggin and Bmp2 mutant mice. Dev Dyn 239(2):505-13. PubMed: 20063299MGI: J:156945
- Hwang CH; Wu DK. 2008. Noggin heterozygous mice: an animal model for congenital conductive hearing loss in humans. Hum Mol Genet 17(6):844-53. PubMed: 18096605MGI: J:132023
- Jiang M; Ku WY; Zhou Z; Dellon ES; Falk GW; Nakagawa H; Wang ML; Liu K; Wang J; Katzka DA; Peters JH; Lan X; Que J. 2015. BMP-driven NRF2 activation in esophageal basal cell differentiation and eosinophilic esophagitis. J Clin Invest 125(4):1557-68. PubMed: 25774506MGI: J:222290
- Kulessa H; Turk G; Hogan BL. 2000. Inhibition of Bmp signaling affects growth and differentiation in the anagen hair follicle. EMBO J 19(24):6664-74. PubMed: 11118201MGI: J:140021
- Lana-Elola E; Tylzanowski P; Takatalo M; Alakurtti K; Veistinen L; Mitsiadis TA; Graf D; Rice R; Luyten FP; Rice DP. 2011. Noggin null allele mice exhibit a microform of holoprosencephaly. Hum Mol Genet 20(20):4005-15. PubMed: 21821669MGI: J:175841
- Li Y; Litingtung Y; Ten Dijke P; Chiang C. 2007. Aberrant Bmp signaling and notochord delamination in the pathogenesis of esophageal atresia. Dev Dyn 236(3):746-54. PubMed: 17260385MGI: J:118341
- Liu Z; Yu S; Manley NR. 2007. Gcm2 is required for the differentiation and survival of parathyroid precursor cells in the parathyroid/thymus primordia. Dev Biol 305(1):333-46. PubMed: 17382312MGI: J:121311
- Matsui M; Klingensmith J. 2014. Multiple tissue-specific requirements for the BMP antagonist Noggin in development of the mammalian craniofacial skeleton. Dev Biol 392(2):168-81. PubMed: 24949938MGI: J:214981
- Mayer JA; Foley J; De La Cruz D; Chuong CM; Widelitz R. 2008. Conversion of the nipple to hair-bearing epithelia by lowering bone morphogenetic protein pathway activity at the dermal-epidermal interface. Am J Pathol 173(5):1339-48. PubMed: 18832580MGI: J:143432
- Mine N; Anderson RM; Klingensmith J. 2008. BMP antagonism is required in both the node and lateral plate mesoderm for mammalian left-right axis establishment. Development 135(14):2425-34. PubMed: 18550712MGI: J:137629
- Ohta S; Suzuki K; Tachibana K; Tanaka H; Yamada G. 2007. Cessation of gastrulation is mediated by suppression of epithelial-mesenchymal transition at the ventral ectodermal ridge. Development 134(24):4315-24. PubMed: 18003744MGI: J:130130
- Patel SR; Gordon J; Mahbub F; Blackburn CC; Manley NR. 2006. Bmp4 and Noggin expression during early thymus and parathyroid organogenesis. Gene Expr Patterns 6(8):794-9. PubMed: 16517216MGI: J:112219
- Plikus MV; Mayer JA; de la Cruz D; Baker RE; Maini PK; Maxson R; Chuong CM. 2008. Cyclic dermal BMP signalling regulates stem cell activation during hair regeneration. Nature 451(7176):340-4. PubMed: 18202659MGI: J:131404
- Rodriguez P; Da Silva S; Oxburgh L; Wang F; Hogan BL; Que J. 2010. BMP signaling in the development of the mouse esophagus and forestomach. Development 137(24):4171-6. PubMed: 21068065MGI: J:166768
- Stottmann RW; Anderson RM; Klingensmith J. 2001. The BMP antagonists Chordin and Noggin have essential but redundant roles in mouse mandibular outgrowth. Dev Biol 240(2):457-73. PubMed: 11784076MGI: J:73669
- Stottmann RW; Berrong M; Matta K; Choi M; Klingensmith J. 2006. The BMP antagonist Noggin promotes cranial and spinal neurulation by distinct mechanisms. Dev Biol 295(2):647-63. PubMed: 16712836MGI: J:110617
- Suzuki K; Bachiller D; Chen YP; Kamikawa M; Ogi H; Haraguchi R; Ogino Y; Minami Y; Mishina Y; Ahn K; Crenshaw EB 3rd; Yamada G. 2003. Regulation of outgrowth and apoptosis for the terminal appendage: external genitalia: development by concerted actions of BMP signaling. (Erratum) Development 130(25):6209-20. PubMed: 14602679MGI: J:87225
- Tylzanowski P; Mebis L; Luyten FP. 2006. The Noggin null mouse phenotype is strain dependent and haploinsufficiency leads to skeletal defects. Dev Dyn 235(6):1599-607. PubMed: 16598734MGI: J:108573
- Wang Y; Liu C; Rohr J; Liu H; He F; Yu J; Sun C; Li L; Gu S; Chen Y. 2011. Tissue interaction is required for glenoid fossa development during temporomandibular joint formation. Dev Dyn 240(11):2466-73. PubMed: 21953591MGI: J:177115
- Weaver M; Batts L; Hogan BL. 2003. Tissue interactions pattern the mesenchyme of the embryonic mouse lung. Dev Biol 258(1):169-84. PubMed: 12781691MGI: J:83697
- White AC; Xu J; Yin Y; Smith C; Schmid G; Ornitz DM. 2006. FGF9 and SHH signaling coordinate lung growth and development through regulation of distinct mesenchymal domains. Development 133(8):1507-17. PubMed: 16540513MGI: J:107406
- Wijgerde M; Karp S; McMahon J; McMahon AP. 2005. Noggin antagonism of BMP4 signaling controls development of the axial skeleton in the mouse. Dev Biol 286(1):149-57. PubMed: 16122729MGI: J:103548
- Wu XB; Li Y; Schneider A; Yu W; Rajendren G; Iqbal J; Yamamoto M; Alam M; Brunet LJ; Blair HC; Zaidi M; Abe E. 2003. Impaired osteoblastic differentiation, reduced bone formation, and severe osteoporosis in noggin-overexpressing mice. J Clin Invest 112(6):924-34. PubMed: 12975477MGI: J:85541
- Yang YP; Anderson RM; Klingensmith J. 2010. BMP antagonism protects Nodal signaling in the gastrula to promote the tissue interactions underlying mammalian forebrain and craniofacial patterning. Hum Mol Genet 19(15):3030-42. PubMed: 20508035MGI: J:161524
- Ybot-Gonzalez P; Gaston-Massuet C; Girdler G; Klingensmith J; Arkell R; Greene ND; Copp AJ. 2007. Neural plate morphogenesis during mouse neurulation is regulated by antagonism of Bmp signalling. Development 134(17):3203-11. PubMed: 17693602MGI: J:124256
- Yi L; Domyan ET; Lewandoski M; Sun X. 2008. Fibroblast growth factor 9 signaling inhibits airway smooth muscle differentiation in mouse lung. Dev Dyn 238(1):123-137. PubMed: 19097117MGI: J:142646
- Yuan G; Yang G; Zheng Y; Zhu X; Chen Z; Zhang Z; Chen Y. 2015. The non-canonical BMP and Wnt/beta-catenin signaling pathways orchestrate early tooth development. Development 142(1):128-39. PubMed: 25428587MGI: J:217590
- Zhu J; Mackem S. 2011. Analysis of mutants with altered shh activity and posterior digit loss supports a biphasic model for shh function as a morphogen and mitogen. Dev Dyn 240(5):1303-10. PubMed: 21509901MGI: J:170964
- Zhu J; Nakamura E; Nguyen MT; Bao X; Akiyama H; Mackem S. 2008. Uncoupling Sonic hedgehog control of pattern and expansion of the developing limb bud. Dev Cell 14(4):624-32. PubMed: 18410737MGI: J:135157
- del Barco Barrantes I; Davidson G; Grone HJ; Westphal H; Niehrs C. 2003. Dkk1 and noggin cooperate in mammalian head induction. Genes Dev 17(18):2239-44. PubMed: 12952897MGI: J:85554