210. Fibroblast growth factor 9 (FGF9) in the developing marsupial

Abstract

The testicular differentiation pathway in mammals is controlled by a complex array of factors acting in multiple signalling pathways. An important group of factors that regulates this process are the fibroblast growth factors (FGFs). In particular, fibroblast growth factor 9 (FGF9) in mice is critical for normal sexual differentiation. Fgf9 is thought to be important in tipping the balance of development in the bipotential gonad down the testis differentiation pathway. In the developing mouse testis, Fgf9 is antagonistic to the expression of the ovarian differentiation factor Wnt4. In order to examine the conserved role of FGF9 in mammalian testis formation, we cloned FGF9 in a marsupial, the tammar wallaby. Tammar FGF9 nucleotide and protein sequences are highly homologous to the human and chicken orthologues. FGF9 is expressed during the period of testicular differentiation and our data shows that FGF9 is upregulated during testicular differentiation in an opposite but complementary manner to that of WNT4 expression. FGF9 protein was widely distributed in the bipotential gonads but become restricted only to the testis as seminiferous cords formed and was markedly downregulated in the ovary as differentiation proceeded. This strongly suggests that FGF9 has a highly conserved and crucial role in male sexual differentiation similar to the mouse, and supports the suggestion that FGF9 is involved with the control of WNT4 expression in a balancing act to direct the developmental outcome of the gonad.