A model for the multiple roles of Blm during zebrafish gonadal development.
During the early stages of ontogenesis ddx4 (formerly vasa) expressing primordial germ cells (PGC) proliferate and migrate from their initial positions adjacent to the yolk syncytial layer to the gonadal mesoderm. There their proliferation continues, while a varying number of these GCs differentiate into stage 1a oocytes resulting in the development of the “juvenile ovary”. A In wild-type fish the number of GCs may further increase to the point where it crosses the threshold required for female fate-determining pathways to activate, resulting in the development of mature ovaries with GC-derived ovarian stem cells (OSC) and mature oocytes. If the threshold is not reached either due to insufficient GC proliferation, or none at all, a major shift in the gonadal environment occurs through which oocytes (and possibly even a subset of GCs) are eliminated via apoptosis. Subsequently, the formation of spermatogonial stem cells (SSC) and Sertoli cells occurs either by (i) differentiation of common OSC and SSC precursors (gonadal stem cells) into SSCs that in turn induce Sertoli cell differentiation in the soma; or (ii) by the transdifferentiation of somatic follicular cells into Sertoli cells that promote SSC differentiation and expansion from gonadal stem cells, thus leading to testis development. A’ In the wild-type testis, SSCs are enveloped by Sertoli cells where they further differentiate into spermatogonia. In this structure, known as a cyst, spermatogonia go through mitotic expansion followed by synchronous meiosis into spermatids. B In Blm loss-of-function individuals, the complete lack of females might be caused by two major factors: (i) the number of GCs never reaches the threshold necessary for female development; and/or (ii) meiotic processes necessary for the formation of oocytes might be compromised in absence of Blm. As we do not know whether the gonads of blm−/− zebrafish do make the initial “detour” through the juvenile ovary stage or not, both possibilities are indicated. B′ A potential explanation for the subfertility of blm−/− males is that in the absence of Blm accurate DNA repair during spermatogonial meiosis is hindered, and therefore cell death is induced.