Regulation and Function of Hox Proteins in Zebrafish Hindbrain Patterning

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The vertebrate brain contains billions of neurons, divided into a myriad of specialized roles. During embryogenesis, one of the most critical events is the differentiation of unique neuronal subtypes, facilitating proper cell migration, axon pathfinding, and neurotransmitter synthesis. Yet, after decades of study, the mechanisms specifying neuronal subtype are incompletely understood. The clustered cranial motor neurons of the vertebrate hindbrain represent a powerful model to address this critical question. The hindbrain is transiently divided into a series of lineage-restricted compartments, which are known as rhombomeres. Each rhombomere segment contains a unique group of neurons. Our research program focus is on the mechanisms that specify the identity of rhombomere 4 (r4), which is the central signaling center within the hindbrain. Experiments done in our laboratory have implicated three key regulators of hindbrain r4 identity. Our lab's experiments implicate Pbx, Hox-1, Fgf, and retinoic acid in specifying proper rhombomere 4 identity. This research proposal will use two projects to investigate this pathway and determine the molecular mechanisms underlying the establishment of the hindbrain signaling center.