| First Author | Hamra FK | Year | 2007 |
| Journal | J Biol Chem | Volume | 282 |
| Issue | 1 | Pages | 721-30 |
| PubMed ID | 17098736 | Mgi Jnum | J:118149 |
| Mgi Id | MGI:3698680 | Doi | 10.1074/jbc.M608398200 |
| Citation | Hamra FK, et al. (2007) Identification of neuregulin as a factor required for formation of aligned spermatogonia. J Biol Chem 282(1):721-30 |
| abstractText | In the absence of somatic cells, medium conditioned by the SNL fibroblast line (SNL-CM) is able to stimulate primary cultures of rat type-A single spermatogonia to develop into chains of aligned spermatogonia at the 8-, 16-, and 32-cell stages. By comparison, medium conditioned by an MSC-1 Sertoli cell line is ineffective. Glial cell line-derived neurotrophic factor (GDNF)-like molecules were identified in SNL-CM and recombinant forms of GDNF, neurturin, and artemin were shown to stimulate formation of aligned spermatogonia, but principally to only the 4- and 8-cell stages. Because SNL-CM and GDNF-like molecules stimulated the formation of spermatogonial chain length differently, we purified components of SNL-CM to identify the additional contributing factor(s). A fraction was isolated that was dependent on GDNF, but required for effective formation of 16- and 32-cell chain lengths. Sequence analysis identified the factor as mouse neuregulin-1. At picomolar concentrations, recombinant neuregulin-1 in combination with GDNF effectively stimulated formation of aligned spermatogonia up to the 32-cell stage. Neuregulin in the absence of GDNF was relatively ineffective. Soluble receptors for neuregulins blocked the effects of GDNF and SNL-CM, suggesting that both neuregulin and GDNF are required for effective formation of long spermatogonial chains. Addition of neuregulin-1 to cultures on MSC-1 feeder layers resulted in spermatogonial behavior similar to that seen on feeder layers of SNL fibroblasts. In fact, SNL cells were found to express 100-fold higher levels of neuregulin-1 transcripts than MSC-1 cells. Thus, we identify neuregulin as a factor required for spermatogonial amplification and differentiation in culture. |
