William D. Snider, MD

Snider

Director and Professor

Research Description

My research focuses on biological actions of neuronal growth factors and signaling mechanisms downstream of receptor tyrosine kinases. One project funded by R01 NS031768-19 is directed at functions of the RAF/MEK/ERK signaling cascade in brain development. Mutations in core pathway components as well as in upstream modulators are associated with variety of neurodevelopmental syndromes collectively known as “Rasopathies”. We have established that MEK/ERK signaling is key mediator of gliogenesis both in the PNS (Neuron 69: 91 -105) and in the CNS (Neuron 75: 1035-1050). More recently we have focused on functions of the cascade in developing cortical neurons and are finding important layer-specific regulation of neuronal morphology and physiology. Our findings have implications for understanding mechanisms of cognitive dysfunction in “Rasopathy” patients and potentially for developing new treatments.

A second project funded by R01 NS050968-09 is focused on functions of GSK-3 in cortical development. GSK-3 is a key hub in multiple signaling cascades including growth factor/RTK and Wnt/β-catenin. GSK-3 is a target of the drug, lithium, used in the treatment of bipolar disorders, and some of the effects of DISC1 (Disrupted  in Schizophrenia -1 ) are thought to be mediated by GSK-3. In mouse genetic experiments we have established the GSK-3 is key regulator of radial progenitor self-renewal and neurogenesis  (Nature Neurosci. 12:1390). We are now exploring biological functions of GSK-3 in developing cortical neurons.

Selected Publications

Ohata S, Nakatani J, Herranz-Pérez V, Cheng J, Belinson H, Inubushi T, Snider WD, García-Verdugo JM, Wynshaw-Boris A, Álvarez-Buylla A (2014).  Loss of Dishevelleds disrupts planar polarity in ependymal motile cilia and results in hydrocephalus.  Neuron  83: 558-571.

Morgan-Smith M, Wu Y, Zhu X, Pringle J, Snider WD (2014).  GSK-3 signaling in developing cortical neurons is essential for radial migration and dendritic orientation.  eLife 2014;3:e02663

Li X, Newbern JM, Wu Y, Morgan-Smith M, Zhong J, Charron J, and Snider WD (2012). MEK is a key regulator of gliogenesis in the developing brain. Neuron 75: 1035-1050 (with accompanying Preview). PMID: 22998872

Newbern JM and Snider WD. (2012) Bers-ERK Schwann cells coordinate nerve regeneration. Neuron 73: 623 – 626. PMID: 22365537

Newbern J, Li X, Shoemaker S, Zhou J, Zhong J, Wu Y, Bonder D, Hollenback S, Coppola G, Geschwind D, Landreth G, Snider WD. (2011) Specific functions for ERK/MAPK signaling during PNS development. Neuron 69: 91 -105 (selected by Faculty of 1000, Must Read, FFa 10). PMID: 21220101

Yokota Y, Eom TY, Stanco A, Kim WY, Rao S, Gashghaei T, Snider WD, Anton ES. (2010). Cdc42 and GSK3 modulate the dynamics of radial  glial growth, inter-radial glial interactions and polarity in the developing cerebral cortex. Development 137:4101-10. PMID: 21062867

Yokota Y, Kim WY, Chen Y, Wang X, Krebs A, Snider W*, Anton ES*. (2009) The Adenomatous Polyposis Coli (APC) Protein is an Essential Regulator of Radial Glial Polarity and Construction of the Cerebral Cortex. Neuron 61: 42 – 56 (selected by Faculty of 1000). * equal contribution. PMID: 19146812

Kim WY, Wang X, Wu Y, Doble B, Patel S, Woodgett J, Snider WD. (2009) GSK-3 is a master regulator of neural progenitor homeostasis. Nat Neurosci 12: 1390 – 1397 (selected by Faculty of 1000, Must read FFa 8). PMID: 19801986


Contact Information

Email
Office: (919) 843-8623
Lab: (919) 843-8624

Administrative Assistant:
(919) 843-8536


Affiliations