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Anorectal malformations caused by defects in sonic hedgehog signaling.
Mo R
,
Kim JH
,
Zhang J
,
Chiang C
,
Hui CC
,
Kim PC
.
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Anorectal malformations are a common clinical problem affecting the development of the distalhindgut in infants. The spectrum of anorectal malformations ranges from the mildly stenotic anus to imperforate anus with a fistula between the urinary and intestinal tracts to the most severe form, persistent cloaca. The etiology, embryology, and pathogenesis of anorectal malformations are poorly understood and controversial. Sonic hedgehog (Shh) is an endoderm-derived signaling molecule that induces mesodermal gene expression in the chick hindgut. However, the role of Shh signaling in mammalian hindgut development is unknown. Here, we show that mutant mice with various defects in the Shh signaling pathway exhibit a spectrum of distalhindgut defects mimicking human anorectal malformations. Shh null-mutant mice display persistent cloaca. Mutant mice lacking Gli2 or Gli3, two zinc finger transcription factors involved in Shh signaling, respectively, exhibit imperforate anus with recto-urethral fistula and anal stenosis. Furthermore, persistent cloaca is also observed in Gli2(-/-);Gli3(+/-), Gli2(+/-);Gli3(-/-), and Gli2(-/-);Gli3(-/-) mice demonstrating a gene dose-dependent effect. Therefore, Shh signaling is essential for normal development of the distalhindgut in mice and mutations affecting Shh signaling produce a spectrum of anorectal malformations that may reveal new insights into their human disease equivalents.
Apelqvist,
Sonic hedgehog directs specialised mesoderm differentiation in the intestine and pancreas.
1997, Pubmed
Apelqvist,
Sonic hedgehog directs specialised mesoderm differentiation in the intestine and pancreas.
1997,
Pubmed
Belloni,
Involvement of the HLXB9 homeobox gene in Currarino syndrome.
2000,
Pubmed
Belloni,
Identification of Sonic hedgehog as a candidate gene responsible for holoprosencephaly.
1996,
Pubmed
Bitgood,
Hedgehog and Bmp genes are coexpressed at many diverse sites of cell-cell interaction in the mouse embryo.
1995,
Pubmed
Chiang,
Cyclopia and defective axial patterning in mice lacking Sonic hedgehog gene function.
1996,
Pubmed
Conlon,
Detection of messenger RNA by in situ hybridization to postimplantation embryo whole mounts.
1993,
Pubmed
Ding,
Diminished Sonic hedgehog signaling and lack of floor plate differentiation in Gli2 mutant mice.
1998,
Pubmed
,
Xenbase
Echelard,
Sonic hedgehog, a member of a family of putative signaling molecules, is implicated in the regulation of CNS polarity.
1993,
Pubmed
Goodrich,
Hedgehog and patched in neural development and disease.
1998,
Pubmed
Grindley,
Evidence for the involvement of the Gli gene family in embryonic mouse lung development.
1997,
Pubmed
,
Xenbase
Hagan,
Mutation analysis and embryonic expression of the HLXB9 Currarino syndrome gene.
2000,
Pubmed
Harrison,
Pancreas dorsal lobe agenesis and abnormal islets of Langerhans in Hlxb9-deficient mice.
1999,
Pubmed
Hebrok,
Notochord repression of endodermal Sonic hedgehog permits pancreas development.
1998,
Pubmed
Hendren,
Cloaca, the most severe degree of imperforate anus: experience with 195 cases.
1998,
Pubmed
Hui,
A mouse model of greig cephalopolysyndactyly syndrome: the extra-toesJ mutation contains an intragenic deletion of the Gli3 gene.
1993,
Pubmed
Hui,
Expression of three mouse homologs of the Drosophila segment polarity gene cubitus interruptus, Gli, Gli-2, and Gli-3, in ectoderm- and mesoderm-derived tissues suggests multiple roles during postimplantation development.
1994,
Pubmed
Kang,
GLI3 frameshift mutations cause autosomal dominant Pallister-Hall syndrome.
1997,
Pubmed
,
Xenbase
Khoury,
A population study of the VACTERL association: evidence for its etiologic heterogeneity.
1983,
Pubmed
Kimmel,
New mouse models of congenital anorectal malformations.
2000,
Pubmed
Kluth,
SD-mice--an animal model for complex anorectal malformations.
1991,
Pubmed
Kluth,
The principles of normal and abnormal hindgut development.
1995,
Pubmed
Kluth,
Current concepts in the embryology of anorectal malformations.
1997,
Pubmed
Kohlhase,
Mutations in the SALL1 putative transcription factor gene cause Townes-Brocks syndrome.
1998,
Pubmed
,
Xenbase
Kubota,
Congenital anomalies in mice induced by etretinate.
2000,
Pubmed
Lambrecht,
The internal sphincter in anorectal malformations: morphologic investigations in neonatal pigs.
1987,
Pubmed
Li,
Selective agenesis of the dorsal pancreas in mice lacking homeobox gene Hlxb9.
1999,
Pubmed
Litingtung,
Sonic hedgehog is essential to foregut development.
1998,
Pubmed
,
Xenbase
Liu,
Critical timing of bladder embryogenesis in an adriamycin-exposed rat fetal model: a clue to the origin of the bladder.
1999,
Pubmed
Meyers,
Differences in left-right axis pathways in mouse and chick: functions of FGF8 and SHH.
1999,
Pubmed
Ming,
Human developmental disorders and the Sonic hedgehog pathway.
1998,
Pubmed
,
Xenbase
Mo,
Specific and redundant functions of Gli2 and Gli3 zinc finger genes in skeletal patterning and development.
1997,
Pubmed
,
Xenbase
Motoyama,
Essential function of Gli2 and Gli3 in the formation of lung, trachea and oesophagus.
1998,
Pubmed
,
Xenbase
Nievelstein,
Normal and abnormal embryonic development of the anorectum in human embryos.
1998,
Pubmed
Pepicelli,
Sonic hedgehog regulates branching morphogenesis in the mammalian lung.
1998,
Pubmed
Ramalho-Santos,
Hedgehog signals regulate multiple aspects of gastrointestinal development.
2000,
Pubmed
Rittler,
VACTERL association, epidemiologic definition and delineation.
1996,
Pubmed
Roberts,
Sonic hedgehog is an endodermal signal inducing Bmp-4 and Hox genes during induction and regionalization of the chick hindgut.
1995,
Pubmed
Roberts,
Epithelial-mesenchymal signaling during the regionalization of the chick gut.
1998,
Pubmed
Roessler,
Mutations in the human Sonic Hedgehog gene cause holoprosencephaly.
1996,
Pubmed
Ross,
A homeobox gene, HLXB9, is the major locus for dominantly inherited sacral agenesis.
1998,
Pubmed
Santulli,
Imperforate anus: a survey from the members of the Surgical Secton of the American Academy of Pediatrics.
1971,
Pubmed
Sasaki,
Regulation of Gli2 and Gli3 activities by an amino-terminal repression domain: implication of Gli2 and Gli3 as primary mediators of Shh signaling.
1999,
Pubmed
,
Xenbase
Schaeren-Wiemers,
A single protocol to detect transcripts of various types and expression levels in neural tissue and cultured cells: in situ hybridization using digoxigenin-labelled cRNA probes.
1993,
Pubmed
Seri,
Exclusion of the Sonic Hedgehog gene as responsible for Currarino syndrome and anorectal malformations with sacral hypodevelopment.
1999,
Pubmed
Thompson,
Teratogenicity of adriamycin and daunomycin in the rat and rabbit.
1978,
Pubmed
Tsukui,
Multiple left-right asymmetry defects in Shh(-/-) mutant mice unveil a convergence of the shh and retinoic acid pathways in the control of Lefty-1.
1999,
Pubmed
Vargas,
Analysis of the human Sonic Hedgehog coding and promoter regions in sacral agenesis, triphalangeal thumb, and mirror polydactyly.
1998,
Pubmed
van der Putte,
Normal and abnormal development of the anorectum.
1986,
Pubmed
