Differential roles for hedgehog signaling in motor neuron development
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Induction of neurons in the correct number and location is essential for the proper development and function of a nervous system. Signaling mediated by the Hedgehog (Hh) family of secreted proteins plays a vital role in the induction of the vertebrate branchiomotor neurons, which are located in the brainstem and regulate chewing, swallowing, and sound production. The Gli family of zinc-finger transcription factors mediates Hh signaling in all vertebrates. For instance, zebrafish gli1 is required for motor neuron specification in the brainstem but not in the spinal cord, whereas mouse gli genes function redundantly for motor neuron development. We examined motor neuron induction in you-too (yot) mutants, which encode dominant repressor forms of Gli2 (Gli2DR), and following morpholino-mediated knockdown of gli3 function. Motor neuron induction at all axial levels was reduced in yot (gli2DR) mutant embryos, and gli1 or gli3 knockdown in yot (gli2DR) mutants resulted in severe or complete loss of motor neurons. These observations demonstrate that Gli activator function (encoded by gli1, gli2, and gli3) is essential for motor neuron induction and Hh-regulated gene expression in zebrafish.