title: Ezh2 orchestrates topographic migration and connectivity of mouse precerebellar neurons.
abstract: We investigated the role of histone methyltransferase Ezh2 in tangential migration of mouse precerebellar pontine nuclei, the main relay between neocortex and cerebellum. By counteracting the sonic hedgehog pathway, Ezh2 represses Netrin1 in dorsal hindbrain, which allows normal pontine neuron migration. In Ezh2 mutants, ectopic Netrin1 derepression results in abnormal migration and supernumerary nuclei integrating in brain circuitry. Moreover, intrinsic topographic organization of pontine nuclei according to rostrocaudal progenitor origin is maintained throughout migration and correlates with patterned cortical input. Ezh2 maintains spatially restricted Hox expression, which, in turn, regulates differential expression of the repulsive receptor Unc5b in migrating neurons; together, they generate subsets with distinct responsiveness to environmental Netrin1. Thus, Ezh2-dependent epigenetic regulation of intrinsic and extrinsic transcriptional programs controls topographic neuronal guidance and connectivity in the cortico-ponto-cerebellar pathway.
authors: Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, 4058 Basel, Switzerland.
authors: Thomas
authors: T
authors: Di Meglio
authors: Claudius F
authors: CF
authors: Kratochwil
authors: Nathalie
authors: N
authors: Vilain
authors: Alberto
authors: A
authors: Loche
authors: Antonio
authors: A
authors: Vitobello
authors: Keisuke
authors: K
authors: Yonehara
authors: Steven M
authors: SM
authors: Hrycaj
authors: Botond
authors: B
authors: Roska
authors: Antoine H F M
authors: AH
authors: Peters
authors: Anne
authors: A
authors: Eichmann
authors: Deneen
authors: D
authors: Wellik
authors: Sebastien
authors: S
authors: Ducret
authors: Filippo M
authors: FM
authors: Rijli
mesh_terms: D000818:Animals; D002465:Cell Movement; D002531:Cerebellum / Q000166:cytology / Q000196:embryology* / Q000378:metabolism; D002540:Cerebral Cortex / Q000196:embryology / Q000502:physiology; D000071221:Enhancer of Zeste Homolog 2 Protein; D044127:Epigenesis, Genetic; D018507:Gene Expression Regulation, Developmental; D005801:Genes, Homeobox; D018398:Homeodomain Proteins / Q000378:metabolism; D020540:Metencephalon / Q000196:embryology; D051379:Mice; D008822:Mice, Transgenic; D009414:Nerve Growth Factors / Q000235:genetics / Q000378:metabolism; D000075386:Netrin Receptors; D000075388:Netrin-1; D009434:Neural Pathways / Q000196:embryology* / Q000502:physiology; D009474:Neurons / Q000502:physiology*; D063151:Polycomb Repressive Complex 2 / Q000235:genetics / Q000378:metabolism*; D011149:Pons / Q000166:cytology / Q000196:embryology* / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D018398:Homeodomain Proteins; D009414:Nerve Growth Factors; D000075386:Netrin Receptors; D011956:Receptors, Cell Surface; D025521:Tumor Suppressor Proteins; D000075388:Netrin-1; D000071221:Enhancer of Zeste Homolog 2 Protein; C498410:Ezh2 protein, mouse; D063151:Polycomb Repressive Complex 2