The precise regulation of neuronal cell number is essential for proper nervous system function. Mutants exhibiting excess neurons in discreet cell populations are useful for studying the genetic control of neuronal production. Moreover, mutants with extra neurons offer an opportunity to analyze the plasticity of neural circuit formation. We have isolated a mutation in zebrafish, loose ends (loe), that results in supernumerary Mauthner cells. Wild-type zebrafish have a bilateral pair of Mauthner cells on either side of the midline in hindbrain rhombomere 4. In contrast, loe mutants have on average five Mauthner cells on either side of the midline. By cloning the loe gene, we will reveal the identity of the molecule causing this defect. To this end, we will place loe on the genetic map of the zebrafish genome to determine whether it corresponds to a known gene. If a known gene is not revealed, we will positionally clone loe. We will also exploit the fact that loe has an increase in Mauthner cells to ask how the presence of these extra cells affects the formation of the escape response circuit. The escape response circuit involves sensory input onto Mauthner cells and Mauthner cell input onto primary motoneurons. We will characterize both the pre- and post-synaptic contacts in loe mutants to elucidate and how the circuit is organized differently due to the presence of extra Mauthner cells.
|Liu, Katharine S; Gray, Michelle; Otto, Stefanie J et al. (2003) Mutations in deadly seven/notch1a reveal developmental plasticity in the escape response circuit. J Neurosci 23:8159-66|