Research project: 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 proposal are: 1) To define the cellular and molecular mechanisms that are responsible for segregation of the early EB precursors from the common placodal field. 2) To take advantage of advanced genetic tools in zebrafish in order to identify novel genes responsible for EB placode and ganglia development. Candidate: I have a long-standing interest in developmental biology. One unifying theme during my graduate and postodoctoral 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 proposal, I will study how Fgf signaling regulates segregation of EB placode precursors from a common progenitor field. This work is a direct extension of my current NRSA fellowship to study roles of Fgf signaling during EB placode development. I plan to continue developing technology that will assist me in studying cranial placodes and ganglia, including generation and testing of zebrafish transgenic lines, which will greatly facilitate the mutagenesis screen proposed during the ROO phase. Following my postdoctoral work, I plan to establish an independent basic research program in an academic setting. I expect that practical and theoretical knowledge gained during the K99 part of the training will help me to jump-start my own independent studies and will also allow me to venture into new aspects of zebrafish biology. Relevance: Sensory component of the parasympathetic nervous system has been implicated in many human disorders, including chronic obstructive pulmonary disease, migraines, bladder overactivity, and erectile dysfunction. Dysfunction in the afferent branch of the parasympathetic system could lead to congestive heart failure or arrhythmia. Thus, uncovering genes that specify EB placodes and ganglia should provide better understanding for the mechanisms underlying these disorders.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Transition Award (R00)
Project #
5R00HD055303-05
Application #
7780317
Study Section
Special Emphasis Panel (NSS)
Program Officer
Henken, Deborah B
Project Start
2007-05-01
Project End
2013-02-28
Budget Start
2010-03-01
Budget End
2013-02-28
Support Year
5
Fiscal Year
2010
Total Cost
$246,509
Indirect Cost
Name
Oregon Health and Science University
Department
Anatomy/Cell Biology
Type
Schools of Medicine
DUNS #
096997515
City
Portland
State
OR
Country
United States
Zip Code
97239
McCarroll, Matthew N; Nechiporuk, Alex V (2013) Fgf3 and Fgf10a work in concert to promote maturation of the epibranchial placodes in zebrafish. PLoS One 8:e85087
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
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
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
McGraw, Hillary F; Drerup, Catherine M; Culbertson, Maya D et al. (2011) Lef1 is required for progenitor cell identity in the zebrafish lateral line primordium. Development 138:3921-30
Dalgin, Gokhan; Ward, Andrea B; Hao, Le T et al. (2011) Zebrafish mnx1 controls cell fate choice in the developing endocrine pancreas. Development 138:4597-608
Mo, Weike; Chen, Fangyi; Nechiporuk, Alex et al. (2010) Quantification of vestibular-induced eye movements in zebrafish larvae. BMC Neurosci 11:110