Genetic dissection of the mechanisms or establishment of the vagus motor nuclei

   The vagus nerve is important as the autonomic center for the maintenance of homeostasis. In mammals, two motor nuclei, the nucleus ambiguous and the dorsal motor nucleus of vagus innervate muscles of branchial arches and parasynpathetic ganglia for control of most of visceral organs including the heart, respectively. Aberrant positioning of these nuclei is implicated in the etiology of the sudden infant death syndrome (SIDS) with severe respiratory disorder. Therefore, control of precursor cell migration into the right positions to establish the stereotyped arrangements of the nuclei may be crucially important for the vagus motor neurons to exert their normal functions. However the genetic program regulating this process is almost unknown.

   The zebrafish embryo also has two vagus motor nuclei as in the case of mammals. In the Islet-1 GFP transgenic fish, which expresses GFP in cranial and spinal motor neurons including the vagus, we can investigate the dorso-laterally and medially located vagus motor nuclei at rhombomere 8th. We can also perform the live imaging for behavior of precursors of these nuclei by using hindbrain explants. We screened zebrafish mutants affecting development of the vagus motor nuclei by saturation mutant screening and isolated interesting mutants showing various aberrant behaviors of the precursors such as overshooting in migration, accumulation defect, and ceasing in migration. To analyze these mutants will disclose molecular mechanisms for development of the vagus motor nuclei.

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Shigeharu Kinoshita