Sry and Signals Controlling the Origin and Specification of Sertoli Cells

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The goal of Dr. Capel's lab is to learn how the male sex determining gene, Sry, controls organogenesis of the testis. Sry is thought to be expressed in precursors of Sertoli cells, the cells believed to play a central role in sex determination by orchestrating male-specific organ development. Recently she has used DiI to lineage trace Sertoli cells and have shown that they arise from the coelomic epithelium of the gonad during a phase of proliferation, a single cell can give rise to a Sertoli and another somatic cell of the testis. In situ expression data suggests that this asymmetric fate decision is under the control of the Notch/Delta pathway. To investigate this possibility, a constitutive Notch gene will be introduced by adenovirus infection in organ culture to test whether overexpression of Notch disrupts commitment to the Sertoli cell fate. XX Sry transgenic experiments show that male-specific proliferation in the gonad depends on Sry. To determine whether Sry's effect on proliferation is cell autonomous and/or non-cell autonomous, proliferation in an XX_SYGFP chimeric gonad will be analyzed. To explore a view in the field that mesonephric tubules represent another source of Sertoli precursors, a transgenic mouse carrying a green fluorescent protein reporter gene under the control of a tubule-specific promoter will be generated. Tubule cells will be marked by GFP such that the fate of these cells can be analyzed. Elucidating the function of the male sex determining switch, Sry, in biological and morphogenetic processes like cell fate decisions, proliferation, and cell reorganization will provide novel information about the molecular genetic mechanisms controlling organogenesis and differentiation.