title: Clonal analysis reveals granule cell behaviors and compartmentalization that determine the folded morphology of the cerebellum.
abstract: The mammalian cerebellum consists of folds of different sizes and shapes that house distinct neural circuits. A crucial factor underlying foliation is the generation of granule cells (gcs), the most numerous neuron type in the brain. We used clonal analysis to uncover global as well as folium size-specific cellular behaviors that underlie cerebellar morphogenesis. Unlike most neural precursors, gc precursors divide symmetrically, accounting for their massive expansion. We found that oriented cell divisions underlie an overall anteroposteriorly polarized growth of the cerebellum and gc clone geometry. Clone geometry is further refined by mediolateral oriented migration and passive dispersion of differentiating gcs. Most strikingly, the base of each fissure acts as a boundary for gc precursor dispersion, which we propose allows each folium to be regulated as a developmental unit. Indeed, the geometry and size of clones in long and short folia are distinct. Moreover, in engrailed 1/2 mutants with shorter folia, clone cell number and geometry are most similar to clones in short folia of wild-type mice. Thus, the cerebellum has a modular mode of development that allows the plane of cell division and number of divisions to be differentially regulated to ensure that the appropriate number of cells are partitioned into each folium.
authors.affiliation: Department of Developmental Biology, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, USA.
authors.forename: Emilie
authors.initials: E
authors.lastname: Legué
authors.affiliation: Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, USA.
authors.forename: Elyn
authors.initials: E
authors.lastname: Riedel
authors.affiliation: Department of Developmental Biology, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, USA joynera@mskcc.org.
authors.forename: Alexandra L
authors.initials: AL
authors.lastname: Joyner
mesh_terms: D000818:Animals; D002455:Cell Division / Q000502:physiology*; D019070:Cell Lineage / Q000502:physiology; D016764:Cell Polarity / Q000502:physiology; D049109:Cell Proliferation / Q000502:physiology*; D002531:Cerebellum / Q000196:embryology*; D021621:Imaging, Three-Dimensional; D007150:Immunohistochemistry; D007395:Interneurons / Q000166:cytology*; D051379:Mice; D008856:Microscopy, Fluorescence; D058953:Neural Stem Cells / Q000502:physiology*; D038081:Organogenesis / Q000502:physiology*; D010671:Phenylurea Compounds
chemical_list: D010671:Phenylurea Compounds; C032766:ethylene diurea
keywords: Engrailed mutants; Foliation; Lineage restriction; Lobules; Morphogenesis; Mouse; Polarized growth
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