○Kentaro Suzuki1 Giovanni Levi2 Hidenao Ogi1 Yukiko Ogino1 Gen Yamada1
Center for Animal Resources and Development (CARD)、IRDA, Kumamoto Univ.1，National Cancer Institute-IST, Advanced Biotechnology Center, Genova, Italy2
External genitalia are regarded as one of the appendages emerging from the posterior body trunk. The external genitalia develop to perform copulation and the transfer of sperm, as well as for uresis. Despite recent progresses in molecular embryology, few attempts have been performed to elucidate the molecular developmental processes of external genitalia formation. Dlx homeobox genes are mammalian homologs of the Drosophila Distal-less (Dll ) gene. The Dlx /Dll gene family is of ancient origin and appears to play a role in appendage development. In Drosophila, Dll is expressed in the distal portion of the developing appendages and is critical for the development of the distal structures. The vertebrate Dlx genes consist of six genes that are organized into the Dlx1/2, Dlx3/4, and Dlx5/6. In situ hybridization analysis showed that Dlx genes were expressed spatio-temporally in developing GT, the embryonic external genital bud. To investigate the roles of Dlxs during GT development, we analyzed the Dlx5/6 double knockout mice GT. Although, there was no obvious abnormality of GT outgrowth, mutants showed defects in the ventral side of GT. These mice demonstrated a significant anomaly in urethral tube and urethral plate, which is necessary for urethra formation. We also observed a marked reduction of cell proliferation and Fgf8 expression in the distal GT mesenchyme at 12.5 dpc in the mutants. Our recent analysis on Dlx genes and its regulatory roles in GT development will be presented.
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