Affiliation:
1. Program in Molecular Medicine and Department of Cell Biology, University of Massachusetts Medical School, 373 Plantation Street, Worcester, MA 01605, USA
Abstract
Delaminated neuroblasts in Drosophila function as stem cells during embryonic central nervous system development. They go through repeated asymmetric divisions to generate multiple ganglion mother cells, which divide only once more to produce postmitotic neurons. Snail, a zinc-finger transcriptional repressor, is a pan-neural protein, based on its extensive expression in neuroblasts. Previous results have demonstrated that Snail and related proteins, Worniu and Escargot, have redundant and essential functions in the nervous system. We show that the Snail family of proteins control central nervous system development by regulating genes involved in asymmetry and cell division of neuroblasts. In mutant embryos that have the three genes deleted, the expression of inscuteable is significantly lowered, while the expression of other genes that participate in asymmetric division, including miranda, staufen and prospero, appears normal. The deletion mutants also have much reduced expression of string, suggesting that a key component that drives neuroblast cell division is abnormal. Consistent with the gene expression defects, the mutant embryos lose the asymmetric localization of prospero RNA in neuroblasts and lose the staining of Prospero protein that is normally present in ganglion mother cells. Simultaneous expression of inscuteable and string in the snail family deletion mutant efficiently restores Prospero expression in ganglion mother cells, demonstrating that the two genes are key targets of Snail in neuroblasts. Mutation of the dCtBP co-repressor interaction motifs in the Snail protein leads to reduction of the Snail function in central nervous system. These results suggest that the Snail family of proteins control both asymmetry and cell division of neuroblasts by activating, probably indirectly, the expression of inscuteable and string.
Publisher
The Company of Biologists
Subject
Developmental Biology,Molecular Biology
Reference50 articles.
1. Alberga, A., Boulay, J.-L., Kempe, E., Dennefeld, C. and Haenlin, M. (1991). The snail gene required for mesoderm formation is expressed dynamically in derivatives of all three germ layers. Development111, 983-992.
2. Ashraf, S. I., Hu, X., Roote, J. and Ip, Y. T. (1999). The mesoderm determinant Snail collaborates with related zinc-finger proteins to control Drosophila neurogenesis. EMBO J.18, 6426-6438.
3. Bhat, K. M. (1998). Cell-cell signaling during neurogenesis: some answers and many questions. Int. J. Dev. Biol.42, 127-139.
4. Boulay, J. L., Dennefeld, C. and Alberga, A. (1987). The Drosophila developmental gene snail encodes a protein with nucleic acid binding fingers. Nature330, 395-398.
5. Cai, Y., Chia, W. and Yang, X. (2001). A family of Snail-related zinc finger proteins regulates two distinct and parallel mechanisms that mediate Drosophila neuroblast asymmetric divisions. EMBO J.20, 1704-1714.
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