Research Overview

Overview

Research Overview 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. In the Siegrist Lab, we are working to understand how the immense number of molecularly and functionally distinct neuron types are produced during development and importantly, how natural environments impact generation of neuron number and diversity in animals living in the real world. Research in the Siegrist lab is focused on the following fundamental themes and questions.


Research Themes


Nutrient-control of neural stem cells in their niche

Nutrient-control of neural stem cells in their niche

Neural stem cells, like other stem cells, switch between quiescence and proliferation as part of their normal developmental program, during adult homeostasis, and for repairing tissue after damage. We are working to understand the lineage-specific NSC intrinsic programs that govern NSC proliferation decisions in response to dietary nutrient availability.

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Temporal identity factors & neurogenesis termination

Temporal identity factors & neurogenesis termination

Neural stem cells express different transcription factors and signaling molecules over time, which allows for sequential generation of different neuron types. We are working to identify additional neural stem cell intrinsic factors that regulate temporal identity and are investigating how dietary nutrients and steroid hormones influence timing of NSC temporal transitions and timing of neurogenesis termination.

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Neuronal circuits involved in nutrient sensing and brain growth control

Neuronal circuits involved in nutrient sensing and brain growth control

Neurosecretory neurons in the brain synthesize and secrete a myriad of neuropeptides, hormones and other neuromodulatory factors that coordinate tissue growth and homeostasis with overall animal growth and physiology. How are these neuronal circuits architected and how do these circuits affect NSC proliferation to coordinate overall brain growth with overall organismal growth?

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Repair and regeneration of adult neural tissues

Repair and regeneration of adult neural tissues

Bones and skin have an amazing ability to self-repair. Even the liver can fully regenerate after a partial hepatectomy. In contrast, neural tissues, including the brain have an extremely limited ability to self-repair. We are working to understand the limited regenerative capacity of adult neural tissues and on developing methods to remake brain structures through reinitiation of developmental neurogenesis.

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Genetic variation in neural developmental programs

Genetic variation in neural developmental programs

Why are not all brains the same even in a given species? Do evolutionary pressures lead to adaptations that manifest in distinct NSC proliferation patterns in response to environmental conditions and ultimately varied brain organization? With these questions in mind, we are working to determine how dietary nutrient availability impacts brain development in laboratory maintained and in wild caught isogenized Drosophila from northern and southern latitudes, whose genomes have been sequenced.

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