Project Grant F31HD123661

VASCULATURE-ASSOCIATED NEURAL CREST-DERIVED PROGENITOR CELL CONTRIBUTIONS TO ZEBRAFISH DEVELOPMENT - PROJECT SUMMARY/ABSTRACT MULTIPOTENT CELLS OF THE NEURAL CREST PLAY CRUCIAL ROLES DURING EMBRYOGENESIS BY CONTRIBUTING TO AN ENORMOUS ARRAY OF TISSUES, INCLUDING THE NEURONS, GLIA AND SCHWANN CELLS OF THE NERVOUS SYSTEM, THE NEUROENDOCRINE SYSTEM, THE BONES, CARTILAGE AND CONNECTIVE TISSUE OF THE HEAD, AND PIGMENT CELLS. DIFFERENTIATION INTO THIS MULTITUDE OF CELL TYPES OCCURS EARLY DURING DEVELOPMENT, BUT MORE RECENT RESEARCH HAS IDENTIFIED POCKETS OF POST-EMBRYONIC NEURAL CREST LINEAGE CELLS THAT RETAIN STEM-LIKE CHARACTERISTICS. THE EARLY NEURAL CREST CONTRIBUTION TO DEVELOPMENT HAS BEEN WELL STUDIED OVER THE DECADES SINCE THIS POPULATION WAS FIRST DESCRIBED, BUT FAR LESS IS KNOWN ABOUT THE ROLES THESE LATER NEURAL CREST DERIVED PROGENITOR POPULATIONS PLAY IN ADULT ORGANISMS. THE GOAL OF THIS PROPOSAL IS TO INVESTIGATE A NEWLY IDENTIFIED POPULATION OF SUCH CELLS IN ZEBRAFISH, WHICH OCCUPY A UNIQUE NICHE, AND WHICH MAY PLAY A ROLE IN BOTH VASCULAR DEVELOPMENT AND HOMEOSTASIS, AND NEURAL CREST DERIVATIVE TISSUE REGENERATION. AIM 1 FOCUSES ON DETERMINING THE NORMAL DEVELOPMENT OF THIS CELL POPULATION. I WILL USE TRANSGENIC FLUORESCENT MARKERS TRACK THEIR MIGRATORY BEHAVIORS ALONG VARIOUS CHANNELS IN LARVAL ZEBRAFISH AS THEY UNDERGO POST-EMBRYONIC PIGMENT PATTERN METAMORPHOSIS, OBSERVE DIFFERENTIATION OF THIS POPULATION OVER MULTIPLE LIFE STAGES, AND DETERMINE IF THEIR DEVELOPMENT AND SURVIVAL DEPEND ON FACTORS ALREADY KNOWN TO BE NECESSARY TO OTHER NEURAL CREST PROGENITOR POPULATIONS. AIM 2 FOCUSES ON ASSESSING THE FUNCTION OF THESE CELLS BY DISRUPTING THIS POPULATION AND ITS ANATOMICAL NEIGHBORS. I WILL ABLATE THE CELLS TO IDENTIFY THE EFFECT ON THE TISSUES THEY CONTACT, IN ADDITION TO ABLATING THE POPULATION OF CELLS WE BELIEVE PRODUCES THE SIGNALS THAT KEEP THIS PROGENITOR POPULATION RELATIVELY UNDIFFERENTIATED, TO POTENTIALLY INDUCE ECTOPIC DIFFERENTIATION. FINALLY, I WILL EXPLORE THE ROLE THIS POPULATION PLAYS IN REGENERATION BY USING LINEAGE TRACING TO IDENTIFY DAUGHTER CELLS THAT CONTRIBUTE TO REPAIR WHEN ANOTHER ADJACENT NEURAL CREST DERIVED TISSUE IS DAMAGED. THESE STUDIES WILL INCREASE OUR KNOWLEDGE OF NEURAL CREST CELL ROLES IN THE POST-EMBRYONIC STAGE.