Palmer, Stephen James; (1992) The cellular basis of sex determination in the mouse. Doctoral thesis (Ph.D), UCL (University College London).

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Abstract

Previous work has shown that in adult XX↔XY chimeras, the XX cell lineage can contribute to all of the testicular somatic cell types except the Sertoli cell population. This led to the hypothesis that the Y chromosome initiates testis formation by cell-autonomously inducing the differentiation of Sertoli cells from their precursors - the supporting cell lineage. In the first project of this thesis, this model was tested by examining the fate of XX cells in the testes of fetal, prepuberal and adult XX↔XY chimeras using in situ hybridization to a transgenic marker. It was found that whilst XX Sertoli cells were strongly selected against, small numbers were found at the fetal and prepuberal stages and very small numbers in adults. The model was tested further in the second project by examining the fate of XY cells in the gonads of XO/XY mosaics using in situ hybridization with a Y-specific probe. In these circumstances, it was found that XY cells contributed to the follicle cell population (the products of the supporting cell lineage in the ovary) in roughly the same proportions as the other somatic lineages examined. It is argued that in the normal XY individual, the Y acts in a cell-autonomous fashion to induce Sertoli cell formation, but this system is 'leaky', causing some local recruitment of XX cells in chimeras. When insufficient Sertoli cells differentiate for testis cord formation, these cells are susceptible to recruitment into the follicle cell pool. In the third experiment, the onset of testicular differentiation in mouse fetuses carrying Y chromosomes derived from M.m.domesticus was compared with fetuses carrying a M.m.muscuius-derived Y. It was found that fetuses with a M.m.domesticus Y chromosome had a relatively late onset of testicular development and it is suggested that this is due to differing alleles of the testis determining gene. It is proposed that the late action of this allele forms the basis of the XY sex reversal which occurs in C57BL/6 mice with a M.m.domesticus-derived Y chromosome.

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