140. GENES CONTROLLING PHALLUS DEVELOPMENT
K. Chew A , A. Pask A B , G. Shaw A and M. B. Renfree AA Zoology, The University of Melbourne, Parkville, VIC, Australia.
B Department of Molecular and Cellular Biology, The University of Connecticut, Storrs, Connecticut, United States.
Reproduction, Fertility and Development 22(9) 58-58 https://doi.org/10.1071/SRB10Abs140
Published: 6 September 2010
Abstract
Abnormalities of the limb and genital urinary tract are amongst the most prevalent congenital birth defects. The phallus and limb are both appendages controlled by similar patterning mechanisms during the early stages of differentiation. However, the phallus later undergoes an androgen dependent masculinisation phase whilst the limb does not. Marsupials deliver altricial young that complete their development after birth so are ideal models to investigate appendage development. In the tammar, development of the phallus occurs after birth during a period when the testicular androgen is low while the young is in the pouch, stages that normally occur in utero in mice. Exposure to androgens during development, but before differentiation of the phallus can induce sex reversal of the female phallus and hypospadias.1 However, the genes controlling development of the phallus and how they interact with the changing androgen environment have not been well studied as yet in any mammal. We are investigating the expression of several key genes, namely SHH, FGF8, BMP4 and DLX5, using RT-PCR, immunohistochemistry and in situ hybridization throughout the differentiation of the phallus and after treatment with androgens. Endogenous application of the potent androgen androstanediol to the phallus resulted in the downregulation of SHH, FGF8, BMP4 and DLX5. These genes are crucial for the correct development of both limb and phallus. However, the limb does not have an androgen dependant phase and it is not sexually dimorphic at these stages. SHH protein was localised in the epithelium of the phallus and in the urethral groove. The expression of the genes patterning the limb and phallus in the tammar therefore appear to be broadly conserved with those of the mouse. However, this is the first identification of androgen-regulated gene expression in the developing mammalian phallus.
(1) Shaw G, Renfree M, Short R, Experimental manipulation of sexual differentiation in wallaby pouch young treated with exogenous steroids. Development, 1988. 104(4): 689.
