Clonal analysis reveals granule cell behaviors and compartmentalization that determine the folded morphology of the cerebellum Journal Article

   

Authors:	Legue, E.; Riedel, E.; Joyner, A. L.
Article 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. © 2015. Published by The Company of Biologists Ltd.
Keywords:	adult; nonhuman; dna synthesis; cell proliferation; animal cell; mouse; mammalia; animal tissue; cerebellum; mus; cell compartmentalization; cell cycle s phase; cell division; cell function; animal experiment; morphogenesis; cell differentiation; stem cell; brain development; granule cell; cell migration; neocortex; anaphase; cell count; cell clone; cell cycle phase; cell expansion; centrosome; cell surface; cell synchronization; dispersion; foliation; lineage restriction; human; female; priority journal; article; engrailed mutants; lobules; polarized growth
Journal Title:	Development
Volume:	142
Issue:	9
ISSN:	0950-1991
Publisher:	Company of Biologists
Date Published:	2015-05-01
Start Page:	1661
End Page:	1671
Language:	English
DOI:	10.1242/dev.120287
PROVIDER:	scopus
PMCID:	PMC4419279
PUBMED:	25834018
DOI/URL:	http://www.scopus.com/inward/record.url?eid=2-s2.0-84928617762&partnerID=40&md5=4355b52acc58f1103ea3390426b19496
Notes:	Export Date: 3 June 2015 -- Source: Scopus

https://synapse.mskcc.org/synapse/works/has_related_data_chk/74177