140. THE DEVELOPMENT OF THE PHALLUS IN A MARSUPIAL

Abstract

The phallus, the limbs and the tail are all considered appendages in the developing mammal. In mice, several key genes including FGF8, BMP4, SHH, DLX5 and DLX6 are known to control the precise pattering of the limb and phallus in the fetus (reviewed in Yamada et al. 2006). The signalling cascade in both appendages begins with SHH interacting with FGF8. In humans, disruptions to these gene pathways result in malformations of both limbs and phallus because these appendages share conserved elements in patterning and development (Yamada et al. 2003). However, this is a poorly researched area so additional models are needed to provide a greater perspective into mammalian embryonic patterning especially of the external genitalia. In marsupials, since most sexual differentiation occurs after birth, the developing phallus and limbs are accessible at stages that occur in utero in humans and other eutherian mammals. We have used the tammar as an alternative model to understand the differentiation of the phallus and limb. FGF8, SHH and megalin mRNA and protein are all expressedin the limb and phallus from the early embryo until post-natal stages. SHH and megalin were co-localised in the urethral epithelium of the tammar phallus. This is the first study to detect megalin in the developing mammalian phallus. SHH is a critical gene in patterning the appendages, and megalin is a transport protein that ferries steroids into the cell where they can bind to their cognate receptor. It has a high affinity for the potent androgen androstanediol, an androgen critical for virilisation of the tammar phallus (Leihy et al. 2004). Further examination is underway to confirm whether the expression of the genes patterning the phallus in the mouse are conserved in the marsupial and whether megalin plays any role in the patterning of the phallus, possibly mediated by SHH.