Hoxa-10 deficient male mice exhibit abnormal development of the accessory sex organs

The role of mammalian Hox genes in regulating segmental patterning of axial structures and the limb is well established. A similar role in development of soft tissue organ systems has recently been suggested by observations l inking several 5' members of the HoxA and HoxD clusters to segmentation eve nts and morphogenesis in the gastrointestinal and genitourinary systems. We have specifically examined the role of Hoxa-10 in development of the male accessory sex organs by characterizing expression of Hoxa-10 in the develop ing male reproductive tract and correlating expression to morphologic abnor malities in knockout mice deficient for Hoxa-10 function. We report that Ho xa-10 expression in the Wolffian duct and urogenital sinus is regionally re stricted and temporally regulated. The domain of expression is defined ante riorly by the caudal epididymis and extends posteriorly to the prostatic an lagen of the urogenital sinus. Expression was maximal at E18 and down-regul ated postnatally, well before accessory sex organ morphogenesis is complete d. Expression in the prostatic anlagen of the urogenital sinus cultured in vitro does not depend upon the presence of testosterone, Loss of Hoxa-10 fu nction is associated with diminished stromal clefting of the seminal vesicl es and decreased size and branching of the coagulating gland. The ductal ar chitecture of the coagulating gland was altered in approximately 30% of mut ants examined and suggests a partial posterior morphologic transformation o f the coagulating gland. We interpret these data to indicate that Hoxa-10 i s expressed in a region specific manner during late gestation and into the perinatal period and that Hoxa-10 is required for normal accessory sex orga n development. Dev Dyn 1999;214:1-12. (C) 1999 Wiley-Liss, Inc.