title: Hoxb13 is required for normal differentiation and secretory function of the ventral prostate.
abstract: The murine prostate is a structure that is made up of four distinct lobes; the dorsal and lateral prostates (often grouped together as the dorsolateral prostate), the anterior (coagulating gland) and the ventral prostate. Previous work has implicated Hox genes in the development of these structures, but how each lobe acquires unique identities for specific functions has not been addressed. In this study, the ventral prostate-specific function of Hoxb13 is described. Mice lacking Hoxb13 function show normal numbers of duct tips, but mice mutant for both Hoxb13 and Hoxd13 exhibit severe hypoplasia of the duct tips, revealing a role for Hoxb13 in ventral prostate morphogenesis. Additionally, a ventral lobe-specific defect was identified in Hoxb13 mutants wherein the epithelium is composed of simple cuboidal cells rather than of tall columnar cells. Ventral prostate ducts appear devoid of contents and do not express the ventral prostate-specific secretory proteins p12, a kazal-type protease inhibitor and p25, a spermine binding protein. These defects are not due to reduction of Nkx3.1 expression or to a global effect on androgen receptor signaling. These results suggest a specific role for Hoxb13 in a differentiation pathway that gives the ventral prostate epithelium a unique identity, as well as a more general role in ventral prostate morphogenesis that is redundant with other Hox13 paralogs.
authors.affiliation: Howard Hughes Medical Institute, Department of Human Genetics, University of Utah, Salt Lake City, Utah 84112, USA.
authors.forename: Kyriakos D
authors.initials: KD
authors.lastname: Economides
authors.forename: Mario R
authors.initials: MR
authors.lastname: Capecchi
mesh_terms: D000818:Animals; D015415:Biomarkers; D002454:Cell Differentiation / Q000502:physiology*; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism / Q000473:pathology; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008297:Male; D051379:Mice; D009154:Mutation; D010641:Phenotype; D011467:Prostate / Q000033:anatomy & histology / Q000254:growth & development* / Q000378:metabolism*; D029584:Prostatic Secretory Proteins / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
chemical_list: D015415:Biomarkers; C484414:HOXB13 protein, human; C513184:HOXD13 protein, human; D018398:Homeodomain Proteins; C100943:Hoxb13 protein, mouse; C084118:Hoxd13 protein, mouse; C491178:NKX3-1 protein, human; C102837:Nkx3-1 protein, mouse; D029584:Prostatic Secretory Proteins; D014157:Transcription Factors