Limiting Self-Renewal

Abstract

Stem cells can undergo symmetric divisions to produce more stem cells or asymmetric division to differentiate into germline cells. Two groups have studied the signals that control this decision during Drosophila spermatogenesis, using temperature-sensitive alleles in flies and germline cell clones with null alleles. Kiger, White-Cooper, and Fuller identified a pathway activated by the Drosophila epidermal growth factor receptor (EGFR) in somatic cyst cells that limits germline cell self-renewal. Mutants of this gene resulted in an expansion of the germline stem cells. However, in isolated germline clones carrying a null EGFR mutation, the germline cells were able to differentiate into spermatids, indicating that the EGFR pathway is activated in the somatic cells, which leads to an extrinsic signal that limits the germline cell self-renewal. Tran, Brenner, and DiNardo found expansion of germline cells in flies with mutant raf alleles. [Raf is a component of the mitogen-activated protein kinase (MAPK) cascade.] As with the EGFR mutants, isolated germline clones with mutant raf genes were capable of differentiating, but in the fly testes these cells failed to differentiate and continued to proliferate as stem cells. Together, these papers suggest a pathway in which the EGFR activates the MAPK cascade through Raf in cyst cells that then leads to an extrinsic signal that controls germline cell self-renewal. Kiger, A.A., White-Cooper, H., and Fuller, M.T. (2000) Somatic support cells restrict germline stem cell self-renewal and promote differentiation. Nature 407 : 750-754. [Online Journal] Tran, J., Brenner, T.J., and DiNardo, S. (2000) Somatic control over the germline stem cell lineage during Drosophila spermatogenesis. Nature 407 : 754-757. [Online Journal]