Defective mesonephric cell migration is associated with abnormal testis cord development in C57BL/6J XYMus (domesticus) mice

During the critical period of mouse sex determination, mesenchymal cells mi grate from the mesonephros into the adjacent developing testis. This proces s is thought to initiate cord development and is dependent on Sry. The pres ence of Sry, however, does not always guarantee normal testis development. For example, transfer of certain Mus domesticus-derived Y chromosomes, i.e. , M. domesticus Sry alleles, onto the C57BL/6J (B6) inbred mouse strain res ults in abnormal testis development. We tested the hypothesis that mesoneph ric cell migration was impaired in three cases representing a range of aber rant testis development: B6 XYAKR, B6 XYPOS, and (BXD-21 x B6-Y-POS)F1 XYPO S. I, each case, mesonephric cell migration was abnormal. Furthermore, the timing, extent, and position of migrating cells in vitro and cord developme nt in vivo were coincident, supporting the hypothesis that mesonephric cell s are critical for cord development. Additional experiments indicated that aberrant testis development results from the inability of Sry(M. domesticus ) to initiate normal cell migration, but that downstream signal transductio n mechanisms are intact. These experiments provide new insight into the mec hanism of C57BL/6J-Y-M. domesticus sex reversal. We present a model incorpo rating these findings as they relate to mammalian sex determination. (C) 20 00 Academic Press.