Retinoic acid induces prostatic bud formation.
Formation of prostatic buds from the urogenital sinus (UGS) to initiate prostate development requires localized action of several morphogenetic factors. This report reveals all-trans-retinoic acid (RA) to be a powerful inducer of mouse prostatic budding that is associated with reciprocal changes in expression of two regulators of budding: sonic hedgehog (Shh) and bone morphogenetic protein 4 (Bmp4). Localization of retinoid signaling and expression of RA synthesis, metabolism, and receptor genes in the UGS on embryonic days 14.5-17.5 implicate RA in the mechanism of bud initiation. In UGS organ culture, RA increased prostatic budding, increased Shh expression, and decreased Bmp4. Prostatic budding was stimulated in the absence of RA by recombinant SHH, by blocking BMP4 signaling with NOGGIN, or by combined treatment with SHH and NOGGIN in UGS organ culture media. These observations suggest that reciprocal changes in hedgehog and BMP signaling by RA may regulate bud initiation.
Vezina
Chad M
CM
School of Pharmacy, University of Wisconsin, Madison, Wisconsin 53705, USA.
Allgeier
Sarah H
SH
Fritz
Wayne A
WA
Moore
Robert W
RW
Strerath
Michael
M
Bushman
Wade
W
Peterson
Richard E
RE
D000445:Aldehyde Oxidoreductases / Q000235:genetics / Q000378:metabolism; D000818:Animals; D000970:Antineoplastic Agents / Q000378:metabolism / Q000494:pharmacology*; D055415:Bone Morphogenetic Protein 4; D019485:Bone Morphogenetic Proteins / Q000235:genetics / Q000378:metabolism*; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D053823:Hedgehog Proteins / Q000235:genetics / Q000378:metabolism*; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009024:Morphogenesis; D011467:Prostate / Q000033:anatomy & histology / Q000187:drug effects* / Q000196:embryology*; D018168:Receptors, Retinoic Acid / Q000235:genetics / Q000378:metabolism; D047488:Retinoid X Receptors / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D046509:Tissue Culture Techniques; D014212:Tretinoin / Q000378:metabolism / Q000494:pharmacology*; D000099176:Noggin Protein
D000445:Aldehyde Oxidoreductases; D000970:Antineoplastic Agents; D055415:Bone Morphogenetic Protein 4; D019485:Bone Morphogenetic Proteins; D002352:Carrier Proteins; D053823:Hedgehog Proteins; D007527:Isoenzymes; D018168:Receptors, Retinoic Acid; D047488:Retinoid X Receptors; D014212:Tretinoin; D000099176:Noggin Protein; C525810:Bmp4 protein, mouse; C465570:Shh protein, mouse