William Talbot

Honors and Awards

• Pew Scholars Award in the Biomedical Sciences, Pew Charitable Trusts (1998-2002)
• Rita Allen Foundation Scholars Award, Rita Allen Foundation (2002-2004)

Professional Education

Postdoctoral Advisees

Kelly Monk

Research Interests

1. Genetic dissection of myelin formation in zebrafish. The myelin sheath allows for rapid axonal conduction in vertebrates. Disruption of myelin underlies important human diseases, including Multiple Sclerosis and hereditary peripheral neuropathy. The formation of myelin, which involves reciprocal signaling between neurons and glial cells, a dramatic morphological transformation of the glial cells, and organization of the axon into different specialized domains, is fascinating but nonetheless poorly understood. We investigate myelination in the zebrafish, a vertebrate model system well suited for large-scale genetic studies and exquisite cellular analysis.

Our goal is to define new genes with essential functions in the development of myelinated nerves using genetic approaches in zebrafish. In genetic screens, we have identified more than 20 mutations that specifically disrupt the development of myelinated nerves. These mutations define at least 15 different genes, indicating that continued screening will identify a large number of new genes. Phenotypic characterization demonstrates that the mutations disrupt a wide array of processes in the developmental progression of myelinating glia, ranging from fate specification through terminal differentiation. Examples of genes defined in the screen include a transcription factor that regulates midline signals important for glial development in the CNS, a receptor tyrosine kinase that controls migration of glial cells along growing axons, and a motor protein that is essential for the morphological specialization of myelinating glial cells. In addition, we are working to positionally clone a mutated gene that is required for the localization of sodium channel proteins at the nodes of Ranvier in myelinated axons.

To elucidate the functions of the mutated genes, we are pursuing detailed phenotypic studies with marker genes, in vivo analysis of transgenes expressing GFP in glia, and electron microscopy...

Publications

• A G protein-coupled receptor is essential for Schwann cells to initiate myelination. Monk KR, Naylor SG, Glenn TD, Mercurio S, Perlin JR, Dominguez C, Moens CB, Talbot WS. Science. 2009; 325 (5946): 1402-5
• Schwann cells inhibit ectopic clustering of axonal sodium channels. Voas MG, Glenn TD, Raphael AR, Talbot WS. J Neurosci. 2009; 29 (46): 14408-14
• Genetic dissection of myelinated axons in zebrafish. Monk KR, Talbot WS. Curr Opin Neurobiol. 2009
• Axonal domains: role for paranodal junction in node of Ranvier assembly. Lyons DA, Talbot WS. Curr Biol. 2008; 18 (18): R876-9
• KBP is essential for axonal structure, outgrowth and maintenance in zebrafish, providing insight into the cellular basis of Goldberg-Shprintzen syndrome. Lyons DA, Naylor SG, Mercurio S, Dominguez C, Talbot WS. Development. 2008; 135 (3): 599-608