In vertebrates, sensory neurons of the parasympathetic epibranchial (EB) ganglia derived from ectodermal placodes are essential for the formation of cranial sensory systems such as smell, somatosensation, and taste. Despite their importance, very little is known about molecular mechanisms that govern various developmental aspects of EB placodes and ganglia. The overall goals of this application are: 1) to define the cellular and molecular mechanisms that are responsible for segregation of the early EB precursors from the common placodal field, and 2) to take advantage of advanced genetic tools in zebrafish in order to identify novel genes responsible for EB placode and ganglia development. ? ? The candidate has a long-standing interest in developmental biology. One unifying theme during his graduate and postdoctoral research was to address the question how naive progenitor cells segregate to give rise to diverse cell types that eventually form an organ. The importance of this question is even more profound when applied to a vertebrate nervous system, where hundreds of cell types exist. During the K99 part of this application, he will study how Fgf signaling regulates segregation of EB placode precursors from a common progenitor field. This work is a direct extension of his current NRSA fellowship to study roles of Fgf signaling during EB placode development. The candidate plans to continue developing technology that will assist him in studying cranial placodes and ganglia, including generation and testing of zebrafish transgenic lines, which will greatly facilitate the mutagenesis screen proposed during the R00 phase. Following postdoctoral work, the candidate plans to establish an independent basic research program in an academic setting. He expects that practical and theoretical knowledge gained during the K99 part of the training will help him to jump-start his own independent studies and will also allow him to venture into new aspects of zebrafish biology. ? ? ?

National Institute of Health (NIH)
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Career Transition Award (K99)
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Pediatrics Subcommittee (CHHD)
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Henken, Deborah B
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University of Washington
Anatomy/Cell Biology
Schools of Medicine
United States
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McCarroll, Matthew N; Lewis, Zachary R; Culbertson, Maya Deza et al. (2012) Graded levels of Pax2a and Pax8 regulate cell differentiation during sensory placode formation. Development 139:2740-50
Harding, Molly J; Nechiporuk, Alex V (2012) Fgfr-Ras-MAPK signaling is required for apical constriction via apical positioning of Rho-associated kinase during mechanosensory organ formation. Development 139:3130-5
Culbertson, Maya D; Lewis, Zachary R; Nechiporuk, Alexei V (2011) Chondrogenic and gliogenic subpopulations of neural crest play distinct roles during the assembly of epibranchial ganglia. PLoS One 6:e24443