title: Genetic mosaic dissection of Lis1 and Ndel1 in neuronal migration.
abstract: Coordinated migration of newly born neurons to their prospective target laminae is a prerequisite for neural circuit assembly in the developing brain. The evolutionarily conserved LIS1/NDEL1 complex is essential for neuronal migration in the mammalian cerebral cortex. The cytoplasmic nature of LIS1 and NDEL1 proteins suggest that they regulate neuronal migration cell autonomously. Here, we extend mosaic analysis with double markers (MADM) to mouse chromosome 11 where Lis1, Ndel1, and 14-3-3ɛ (encoding a LIS1/NDEL1 signaling partner) are located. Analyses of sparse and uniquely labeled mutant cells in mosaic animals reveal distinct cell-autonomous functions for these three genes. Lis1 regulates neuronal migration efficiency in a dose-dependent manner, while Ndel1 is essential for a specific, previously uncharacterized, late step of neuronal migration: entry into the target lamina. Comparisons with previous genetic perturbations of Lis1 and Ndel1 also suggest a surprising degree of cell-nonautonomous function for these proteins in regulating neuronal migration.
authors.affiliation: Howard Hughes Medical Institute and Department of Biology, Stanford University, Stanford, CA 94305, USA.
authors.forename: Simon
authors.initials: S
authors.lastname: Hippenmeyer
authors.forename: Yong Ha
authors.initials: YH
authors.lastname: Youn
authors.forename: Hyang Mi
authors.initials: HM
authors.lastname: Moon
authors.forename: Kazunari
authors.initials: K
authors.lastname: Miyamichi
authors.forename: Hui
authors.initials: H
authors.lastname: Zong
authors.forename: Anthony
authors.initials: A
authors.lastname: Wynshaw-Boris
authors.forename: Liqun
authors.initials: L
authors.lastname: Luo
mesh_terms: D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase / Q000235:genetics / Q000502:physiology*; D000818:Animals; D000831:Animals, Newborn; D001253:Astrocytes / Q000166:cytology / Q000378:metabolism / Q000502:physiology; D002352:Carrier Proteins / Q000235:genetics / Q000502:physiology*; D002465:Cell Movement / Q000502:physiology*; D002540:Cerebral Cortex / Q000166:cytology / Q000378:metabolism / Q000502:physiology; D005260:Female; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000502:physiology*; D009030:Mosaicism; D009474:Neurons / Q000166:cytology / Q000378:metabolism / Q000502:physiology*
chemical_list: D002352:Carrier Proteins; D008869:Microtubule-Associated Proteins; C486015:Ndel1 protein, mouse; D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase; C513190:Pafah1b1 protein, mouse