title: Calm1 signaling pathway is essential for the migration of mouse precerebellar neurons.
abstract: The calcium ion regulates many aspects of neuronal migration, which is an indispensable process in the development of the nervous system. Calmodulin (CaM) is a multifunctional calcium ion sensor that transduces much of the signal. To better understand the role of Ca(2+)-CaM in neuronal migration, we investigated mouse precerebellar neurons (PCNs), which undergo stereotyped, long-distance migration to reach their final position in the developing hindbrain. In mammals, CaM is encoded by three non-allelic CaM (Calm) genes (Calm1, Calm2 and Calm3), which produce an identical protein with no amino acid substitutions. We found that these CaM genes are expressed in migrating PCNs. When the expression of CaM from this multigene family was inhibited by RNAi-mediated acute knockdown, inhibition of Calm1 but not the other two genes caused defective PCN migration. Many PCNs treated with Calm1 shRNA failed to complete their circumferential tangential migration and thus failed to reach their prospective target position. Those that did reach the target position failed to invade the depth of the hindbrain through the required radial migration. Overall, our results suggest the participation of CaM in both the tangential and radial migration of PCNs.
authors.affiliation: Graduate School of Frontier Biosciences, Osaka University, Suita, Osaka 565-0871, Japan hirokob@fbs.osaka-u.ac.jp.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Kobayashi
authors.affiliation: Graduate School of Frontier Biosciences, Osaka University, Suita, Osaka 565-0871, Japan.
authors.forename: Shunsuke
authors.initials: S
authors.lastname: Saragai
authors.affiliation: Graduate School of Frontier Biosciences, Osaka University, Suita, Osaka 565-0871, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Naito
authors.affiliation: Graduate School of Frontier Biosciences, Osaka University, Suita, Osaka 565-0871, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Ichio
authors.affiliation: Graduate School of Frontier Biosciences, Osaka University, Suita, Osaka 565-0871, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Kawauchi
authors.affiliation: Graduate School of Frontier Biosciences, Osaka University, Suita, Osaka 565-0871, Japan.
authors.forename: Fujio
authors.initials: F
authors.lastname: Murakami
mesh_terms: D000818:Animals; D019556:COS Cells; D002118:Calcium / Q000378:metabolism; D002147:Calmodulin / Q000378:metabolism*; D002465:Cell Movement / Q000502:physiology*; D002531:Cerebellum / Q000196:embryology*; D002522:Chlorocebus aethiops; D017931:DNA Primers / Q000235:genetics; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D051379:Mice; D009474:Neurons / Q000502:physiology*; D010957:Plasmids / Q000235:genetics; D034622:RNA Interference; D015398:Signal Transduction / Q000502:physiology*
chemical_list: C000595843:Calm1 protein, mouse; D002147:Calmodulin; D017931:DNA Primers; D002118:Calcium
keywords: Calcium signaling; Calm1; Migration; Pontine nuclei; Precerebellar neuron