Neurons in the inferior olivary nuclei (IO neurons) send climbing fibers to Purkinje cells to elicit functions of the cerebellum. IO neurons and Purkinje cells are derived from neural progenitors expressing the proneural gene ptf1a. In this study, we found that the homeobox gene gsx2 was co-expressed with ptf1a in IO progenitors in zebrafish. Both gsx2 and ptf1a zebrafish mutants showed a strong reduction or loss of IO neurons. The expression of ptf1a was not affected in gsx2 mutants and vice versa. In IO progenitors, the ptf1a mutation increased apoptosis whereas the gsx2 mutation did not, suggesting that ptf1a and gsx2 are regulated independently of each other and have distinct roles. The fibroblast growth factors (Fgf) 3/8a and retinoic acid signals negatively and positively, respectively, regulated gsx2 expression and thereby the development of IO neurons. mafba and hox genes are at least partly involved in the Fgf- and retinoic acid-dependent regulation of IO neuronal development. Our results indicate that gsx2 mediates the rostro-caudal positional signals to specify the identity of IO neurons from ptf1a-expressing neural progenitors.

The homeobox gene gsx2 mediates rostro-caudal positional signaling to specify the identify of neurons in the inferior olivary nuclei from neural progenitors expressing the proneural gene ptf1a. 2 ABSTRACTNeurons in the inferior olivary nuclei (IO neurons) send climbing fibers to Purkinje cells to elicit functions of the cerebellum. IO neurons and Purkinje cells are derived from neural progenitors expressing the proneural gene ptf1a. In this study, we found that the homeobox gene gsx2 was co-expressed with ptf1a in IO progenitors in zebrafish.Both gsx2 and ptf1a zebrafish mutants showed a strong reduction or loss of IO neurons.The expression of ptf1a was not affected in gsx2 mutants and vice versa. In IO progenitors, the ptf1a mutation increased apoptosis whereas the gsx2 mutation did not, suggesting that ptf1a and gsx2 are independently regulated and have distinct roles. The fibroblast growth factors (Fgf) 3/8a and retinoic acid signals negatively and positively, respectively, regulated gsx2 expression and thereby the development of IO neurons.mafba and hox genes are at least partly involved in the Fgf-and retinoic acid-dependent regulation of IO neuronal development. Our results indicate that gsx2 mediates the rostro-caudal positional signals to specify the identity of IO neurons from ptf1a-expressing neural progenitors. K., Suster, M. L., Mizusawa, K., Nagayoshi, S., Kotani, T., Urasaki, A., Kishimoto, Y., Hibi, M. and Kawakami, K. (2008). Genetic dissection of neural circuits by Tol2 transposon-mediated Gal4 gene and enhancer trapping in zebrafish. . Anatomy of zebrafish cerebellum and screen for mutations affecting its development. Dev . Biol. 330, 406-426. Begemann, G., Marx, M., Mebus, K., Meyer, A. and Bastmeyer, M. (2004). Beyond the neckless phenotype: influence of reduced retinoic acid signaling on motor neuron development in the zebrafish hindbrain. Dev. Biol. 271, 119-129. Asakawa,