Corey Harwell, PhD

Assoc Professor in Residence
Neurology
+1 415 476-0768
Research Overview: 

We are interested in understanding how the extensive morphological, molecular and functional diversity of neural cell types is achieved during development of the central nervous system. We focus our studies on the forebrain, with particular attention to the cortex and the septal nucleus of the basal forebrain. Our long-term goal is to understand how genetic and epigenetic programs associated with a progenitor cells spatial and temporal identity dictates their fate choice. We are also interested in understanding how these diverse groups of neurons and glia coordinate to assemble the precise circuitry of the mammalian forebrain.

Project 1
Genetic and epigenetic regulation of neural cell fate specification.
Radial glial cells serve as the primary neural progenitors of the central nervous system. Radial glial cells transition through a series of competence states as they undergo multiple divisions to produce clonal lineages composed of diverse neural cell types. We are interested in understanding how progenitors ‘know’ when to switch from producing one neural cell type to another. We are also interested in understanding how epigenetic modifications in progenitors to provide instructions to their neuronal progeny important for fate specification.

Project 2
Developmental diversity of spatial and temporal lineages in the septum.
Septal nuclei in the basal forebrain have critical roles in regulating emotional and motivational states. The septum is composed of a diverse array of GABAergic, cholinergic and glutamatergic projection neurons. We know very little about the specific functions the diverse groups septal neuron types and even less about the developmental mechanisms that create this diversity. We are interested in understanding the molecular programs involved in specifying these distinct projection neuron subgroups, and how their circuitry and functional properties regulates innate behaviors.

Project 3
Neuron-glia crosstalk during cortical circuit assembly.
The nervous system is comprised of two main cell types, neurons and glia. Neurons connected through chemical and electrical synapses form complex networks in the brain. Glial cells have a broad range of functions that influence the formation and activity of neuronal networks. Astrocytes are the most numerous and diverse glial cell in the mammalian brain. They have crucial roles in regulation synapse formation and pruning. The mechanism by which astrocytes  and neurons communicate and coordinate with  is not well understood. We are interested in uncovering the secreted signals that neurons and astrocytes use to communicate, and the specific ‘messages’ encoded by those factors.

Primary Thematic Area: 
Neurobiology
Secondary Thematic Area: 
Developmental & Stem Cell Biology
Research Summary: 
Molecular regulation of neural cell fate and circuit assembly
Publications: 

Astrocyte-neuron crosstalk through Hedgehog signaling mediates cortical synapse development.

Cell reports

Xie Y, Kuan AT, Wang W, Herbert ZT, Mosto O, Olukoya O, Adam M, Vu S, Kim M, Tran D, Gómez N, Charpentier C, Sorour I, Lacey TE, Tolstorukov MY, Sabatini BL, Lee WA, Harwell CC

Transcriptional profiling of sequentially generated septal neuron fates.

eLife

Turrero García M, Stegmann SK, Lacey TE, Reid CM, Hrvatin S, Weinreb C, Adam MA, Nagy MA, Harwell CC

The Eya1 Phosphatase Mediates Shh-Driven Symmetric Cell Division of Cerebellar Granule Cell Precursors.

Developmental neuroscience

Merk DJ, Zhou P, Cohen SM, Pazyra-Murphy MF, Hwang GH, Rehm KJ, Alfaro J, Reid CM, Zhao X, Park E, Xu PX, Chan JA, Eck MJ, Nazemi KJ, Harwell CC, Segal RA

Transcriptional regulation of MGE progenitor proliferation by PRDM16 controls cortical GABAergic interneuron production.

Development (Cambridge, England)

Turrero García M, Baizabal JM, Tran DN, Peixoto R, Wang W, Xie Y, Adam MA, English LA, Reid CM, Brito SI, Booker MA, Tolstorukov MY, Harwell CC