title: Tail gut endoderm and gut/genitourinary/tail development: a new tissue-specific role for Hoxa13.
abstract: Hoxa13 is expressed early in the caudal mesoderm and endoderm of the developing hindgut. The tissue-specific roles of Hoxa13 function have not been described. Hand-foot-genital syndrome, a rare dominantly inherited human malformation syndrome characterized by distal extremity and genitourinary anomalies, is caused by mutations in the HOXA13 gene. We show evidence that one specific HOXA13 mutation likely acts as a dominant negative in vivo. When chick HFGa13 is overexpressed in the chick caudal endoderm early in development, caudal structural malformations occur. The phenotype is specific to HFGa13 expression in the posterior endoderm, and includes taillessness and severe gut/genitourinary (GGU) malformations. Finally, we show that chick HFGa13 negatively regulates expression of Hoxd13 and antagonizes functions of both endogenous Hoxa13 and Hoxd13 proteins. We suggest a fundamental role for epithelial specific expression of Hoxa13 in the epithelial-mesenchymal interaction necessary for tail growth and posterior GGU patterning.
authors.affiliation: Department of Pathology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
authors.forename: Pascal
authors.initials: P
authors.lastname: de Santa Barbara
authors.forename: Drucilla J
authors.initials: DJ
authors.lastname: Roberts
mesh_terms: D000015:Abnormalities, Multiple / Q000209:etiology* / Q000235:genetics; D000818:Animals; D019521:Body Patterning; D002642:Chick Embryo; D004707:Endoderm / Q000502:physiology; D005121:Extremities / Q000196:embryology; D051524:Fibroblast Growth Factor 8; D005346:Fibroblast Growth Factors / Q000378:metabolism; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007422:Intestines / Q000196:embryology; D017880:Limb Deformities, Congenital / Q000209:etiology / Q000235:genetics; D008969:Molecular Sequence Data; D009154:Mutation; D017384:Sequence Deletion; D013577:Syndrome; D013623:Tail / Q000002:abnormalities / Q000196:embryology; D014157:Transcription Factors; D014564:Urogenital Abnormalities / Q000209:etiology / Q000235:genetics; D014566:Urogenital System / Q000196:embryology
chemical_list: C496456:FGF8 protein, human; C513184:HOXD13 protein, human; D018398:Homeodomain Proteins; C491536:NKX3-2 protein, human; D014157:Transcription Factors; C099959:homeobox protein HOXA13; D051524:Fibroblast Growth Factor 8; D005346:Fibroblast Growth Factors