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Siegrist, Sarah

Sarah Siegrist

Primary Appointment

Biology

Contact Information

Telephone: (434) 982-2604
Email: ses4gr@virginia.edu
Website: http://www.siegristlab.com

Research Interests

Regulation of neural stem cell proliferation during development and adulthood

Research Description

Basic, autonomous and higher, voluntary cognitive functions of the brain require production of an immense diversity of neuron types at the right place and time, as well as correct wiring of these neurons into an array of functional neuronal circuits. Cell division of undifferentiated neural stem cells (NSCs) and committed neural progenitors drives neuron production. It is well accepted that abnormal NSC and progenitor division patterns in space and time are associated with neurodevelopmental disorders, including microcephaly and autism, as well as neurodegenerative disease and cancer. Stem cell therapies are gaining traction as potential treatment options, but uncontrolled, rampant stem cell division or production of the wrong neuron types pose risks with serious consequences. There have been tremendous advances in our understanding of NSC proliferation regulation from in vitro and in vivo studies of the brain, and more recently from organoid cultures, but our understanding of how NSC proliferation decisions are coordinated within the context of whole animal physiology during development and in adulthood is still rudimentary. In particular, it remains unclear how NSC intrinsic programs integrate with NSC extrinsic factors, local and systemic, to control number and type of neurons produced in time and space. To better understand NSC regulation in intact brains in whole organisms during development and aging, under normal versus diseased states, and in response to changing natural environments, the use of multi-disciplinary approaches and appropriate model systems is paramount. Research in the Siegrist lab is focused on the following fundamental themes and questions: 1. Nutrient-dependent control of NSCs in their niche. 2. Intrinsic genetic programs and temporal identity factors that control NSC proliferation timing and neuronal diversity. 3. Neural circuits involved in nutrient sensing and brain growth control. 4. Evolution and adaptation of NSC temporal patterning with developmental timing.

Selected Publications

Siegrist SE, Termination of Drosophila mushroom body neurogenesis via autophagy and apoptosis., 2019; Autophagy. () 1-2 PMID: 31096820 |

Pahl MC, Doyle SE, Siegrist SE, E93 Integrates Neuroblast Intrinsic State with Developmental Time to Terminate MB Neurogenesis via Autophagy., 2019; Current biology : CB. 29(5) 750-762.e3 PMID: 30773368 | PMCID: PMC6428584

Sipe CW, Siegrist SE, Eyeless uncouples mushroom body neuroblast proliferation from dietary amino acids in Drosophila., 2017; eLife. 6() PMID: 28826476 | PMCID: PMC5576483

Janssens DH, Hamm DC, Anhezini L, Xiao Q, Siller KH, Siegrist SE, Harrison MM, Lee CY, An Hdac1/Rpd3-Poised Circuit Balances Continual Self-Renewal and Rapid Restriction of Developmental Potential during Asymmetric Stem Cell Division., 2017; Developmental cell. 40(4) 367-380.e7 PMID: 28245922 | PMCID: PMC5336133

Doyle SE, Pahl MC, Siller KH, Ardiff L, Siegrist SE, Neuroblast niche position is controlled by Phosphoinositide 3-kinase-dependent DE-Cadherin adhesion., 2017; Development (Cambridge, England). 144(5) 820-829 PMID: 28126840 | PMCID: PMC5374343

Siegrist SE, Haque NS, Chen CH, Hay BA, Hariharan IK, Inactivation of both Foxo and reaper promotes long-term adult neurogenesis in Drosophila., 2010; Current biology : CB. 20(7) 643-8 PMID: 20346676 | PMCID: PMC2862284

Siegrist SE, Doe CQ, Microtubule-induced cortical cell polarity., 2007; Genes & development. 21(5) 483-96 PMID: 17344411 |

Lee CY, Wilkinson BD, Siegrist SE, Wharton RP, Doe CQ, Brat is a Miranda cargo protein that promotes neuronal differentiation and inhibits neuroblast self-renewal., 2006; Developmental cell. 10(4) 441-9 PMID: 16549393 |

Siegrist SE, Doe CQ, Extrinsic cues orient the cell division axis in Drosophila embryonic neuroblasts., 2006; Development (Cambridge, England). 133(3) 529-36 PMID: 16396904 |

Siegrist SE, Doe CQ, Microtubule-induced Pins/Galphai cortical polarity in Drosophila neuroblasts., 2005; Cell. 123(7) 1323-35 PMID: 16377571 |

Renfranz PJ, Siegrist SE, Stronach BE, Macalma T, Beckerle MC, Molecular and phylogenetic characterization of Zyx102, a Drosophila orthologue of the zyxin family that interacts with Drosophila Enabled., 2003; Gene. 305(1) 13-26 PMID: 12594038 |

Stronach BE, Siegrist SE, Beckerle MC, Two muscle-specific LIM proteins in Drosophila., 1996; The Journal of cell biology. 134(5) 1179-95 PMID: 8794860 | PMCID: PMC2120973