Maternal Nanos represses hid/skl-dependent apoptosis to maintain the germ line in Drosophila embryos

doi:10.1073/pnas.0610052104

Maternal Nanos represses hid/skl-dependent apoptosis to maintain the germ line in Drosophila embryos

*Okazaki Institute for Integrative Bioscience, National Institute for Basic Biology, National Institutes of Natural Sciences, Higashiyama, Myodaiji, Okazaki 444-8787, Japan;
^‡Division of Translational Research, Research Center for Genomic Medicine, Saitama Medical University, 1397-1 Yamane, Hidaka, Saitama 350-1241, Japan; and
^§Core Research for Evolutional Science and Technology (CREST), Japan Science and Technology Agency, Honcho, Kawaguchi 332-0012, Japan

Edited by Allan C. Spradling, Carnegie Institution of Washington, Baltimore, MD, and approved March 11, 2007 (received for review November 13, 2006)

Abstract

Nanos (Nos) is an evolutionarily conserved protein essential for the survival of primordial germ cells. In Drosophila, maternal Nos partitions into pole cells and suppresses apoptosis to permit proper germ-line development. However, how this critical event is regulated by Nos has remained elusive. Here, we report that Nos represses apoptosis of pole cells by suppressing translation of head involution defective (hid), a member of the RHG gene family that is required for Caspase activation. In addition, we demonstrate that hid acts in concert with another RHG gene, sickle (skl), to induce apoptosis. Expression of skl is induced in pole cells by maternal tao-1, a ste20-like serine/threonine kinase. Tao-1-dependent skl expression is required to potentiate hid activity. However, skl expression is largely suppressed in normal pole cells. Once the pole cells lack maternal Nos, Tao-1-dependent skl expression is fully activated, suggesting that skl expression is also restricted by Nos. These findings provide the first evidence that the germ line is maintained through the regulated expression of RHG genes.

Footnotes

^¶To whom correspondence should be addressed. E-mail: skob{at}nibb.ac.jp
Author contributions: K.S. and Y.H. contributed equally to this work; K.S., Y.H., and S.K. designed research; K.S., Y.H., Y.N., S.S., K.A., and M.M. performed research; S.S. contributed new reagents/analytic tools; K.S., Y.H., Y.N., S.S., and S.K. analyzed data; and K.S. and S.K. wrote the paper.
↵ ^†Present address: Department of Genetics, Cell Biology, and Development, University of Minnesota, 6-160 Jackson Hall, 321 Church Street SE, Minneapolis, MN 55455.
The authors declare no conflict of interest.
This article is a PNAS Direct Submission.
Data deposition: The sequences reported in this paper have been deposited in the GenBank database (accession nos. AB277547–AB277548). The microarray data have been deposited in the Gene Expression Omnibus (GEO) database, www.ncbi.nlm.nih.gov/geo (accession no. GSE7318).
This article contains supporting information online at www.pnas.org/cgi/content/full/0610052104/DC1.
Abbreviations:

IAP,

inhibitor of apoptosis protein;

NRE,

Nos response element;

PGC,

primordial germ cell.
Freely available online through the PNAS open access option.