Neurotrophin Signaling is Required for the Correct Formation of the Precerebellar Nuclei in Mouse Embryos.

BACKGROUND:In the developing brain, neuronal migration is one of the critical steps in the establishment of an accurate neural network. When neurons reach their final destination, they form layered structures or nuclei. Precerebellar neurons (PCNs) form several nuclei in the pons and medulla and project mossy and climbing fibers to the cerebellum. PCNs originate from the lower rhombic lip in the dorsal hindbrain and migrate tangentially toward their destinations. When PCNs reach their presumptive nucleus-forming region, they change their migration direction from tangential to radial to form the precerebellar nuclei. Although various molecules have been shown to control PCN migration and nucleogenesis, the mechanisms underlying the development of the precerebellar system remain largely unknown. RESULTS:We investigated the possible roles of two members of the neurotrophin family, brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3), in PCN development in mouse embryos. We found that Bdnf and Ntf3, which encode BDNF and NT-3, respectively, are expressed in their nucleus-forming regions in the pons and medulla, whereas their receptor genes are expressed in migrating PCNs. Disrupting these genes singly or in combination led to abnormal nucleogenesis of PCNs. CONCLUSION:Our findings indicate that neurotrophin signaling is required for accurate formation of the precerebellar nuclei.