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The sheer number and diversity of cell types within the human brain is staggering. Understanding how cellular diversity is generated and organized in such a way that allows organisms to think and behave is of fundamental importance. All neurons within the brain are generated from neural stem cells, which are self-renewing multi-potent progenitors. Neural stem cells play a key role in regulating brain size and cell type diversity, since this population remains actively engaged in the cell cycle throughout development. While much effort is geared towards identifying molecular mechanisms regulating stem cell self-renewal, research in my lab is focused on the converse. What are the molecular mechanisms that terminate neural stem cell divisions once development is complete, which is essential for ensuring proper formation of brain circuitry and to inhibit tissue overgrowth and tumorigenesis. Beyond development, the answer to this fundamental question is of key importance for understanding age-related cognitive declines, mood disorders, and limited regenerative capacity of adult brains. Overall, research in the lab is geared towards gaining a greater understanding of:
(1) Regulation of neural stem cell proliferation by extracellular factors, local and systemic.
(2) Intrinsic signaling programs regulating neural stem cell fate decisions: death versus survival.
(3) Functional and molecular similarities between Drosophila and mammalian neural stem cells
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- Siegrist S, Doe C. Microtubule-induced cortical cell polarity. Genes & development. 2007;21(5): 483-96. PMID: 17344411
- Lee C, Wilkinson B, Siegrist S, Wharton R, Doe C. Brat is a Miranda cargo protein that promotes neuronal differentiation and inhibits neuroblast self-renewal. Developmental cell. 2006;10(4): 441-9. PMID: 16549393
- Siegrist S, Doe C. Extrinsic cues orient the cell division axis in Drosophila embryonic neuroblasts. Development (Cambridge, England). 2006;133(3): 529-36. PMID: 16396904
- Siegrist S, Doe C. Microtubule-induced Pins/Galphai cortical polarity in Drosophila neuroblasts. Cell. 2005;123(7): 1323-35. PMID: 16377571
- Renfranz P, Siegrist S, Stronach B, Macalma T, Beckerle M. Molecular and phylogenetic characterization of Zyx102, a Drosophila orthologue of the zyxin family that interacts with Drosophila Enabled. Gene. 2003;305(1): 13-26. PMID: 12594038
- Stronach B, Siegrist S, Beckerle M. Two muscle-specific LIM proteins in Drosophila. The Journal of cell biology. 1996;134(5): 1179-95. PMID: 8794860 | PMCID: PMC2120973