The Engrailed homeobox genes determine the different foliation patterns in the vermis and hemispheres of the mammalian cerebellum Journal Article


Authors: Cheng, Y.; Sudarov, A.; Szulc, K. U.; Sgaier, S. K.; Stephen, D.; Turnbull, D. H.; Joyner, A. L.
Article Title: The Engrailed homeobox genes determine the different foliation patterns in the vermis and hemispheres of the mammalian cerebellum
Abstract: Little is known about the genetic pathways and cellular processes responsible for regional differences in cerebellum foliation, which interestingly are accompanied by regionally distinct afferent circuitry. We have identified the Engrailed (En) homeobox genes as being crucial to producing the distinct medial vermis and lateral hemisphere foliation patterns in mammalian cerebella. By producing a series of temporal conditional mutants in En1 and/or En2, we demonstrate that both En genes are required to ensure that folia exclusive to the vermis or hemispheres form in the appropriate mediolateral position. Furthermore, En1/En2 continue to regulate foliation after embryonic day 14, at which time Fgf8 isthmic organizer activity is complete and the major output cells of the cerebellar cortex have been specified. Changes in spatially restricted gene expression occur prior to foliation in mutants, and foliation is altered from the onset and is accompanied by changes in the thickness of the layer of proliferating granule cell precursors. In addition, the positioning and timing of fissure formation are altered. Thus, the En genes represent a new class of genes that are fundamental to patterning cerebellum foliation throughout the mediolateral axis and that act late in development. © 2010. Published by The Company of Biologists Ltd.
Keywords: controlled study; unclassified drug; mutation; nonhuman; cell proliferation; animal cell; mouse; mammalia; animals; mice; animal tissue; cerebellum; gene expression; embryo; nerve tissue proteins; embryo pattern formation; morphogenesis; homeodomain proteins; transcription factors; stem cell; gene expression regulation, developmental; brain development; granule cell; embryo, mammalian; homeodomain protein; sonic hedgehog; erinaceidae; cerebellum development; body patterning; mutant; fibroblast growth factor 8; genes, homeobox; en; fgf8; granule cells; engrailed 1 homeodomain protein; engrailed 2 homeodomain protein; cerebellum foliation pattern; cerebellum hemisphere; cerebellum vermis; cerebellar cortex; epicoccum
Journal Title: Development
Volume: 137
Issue: 3
ISSN: 0950-1991
Publisher: Company of Biologists  
Date Published: 2010-02-01
Start Page: 519
End Page: 529
Language: English
DOI: 10.1242/dev.027045
PUBMED: 20081196
PROVIDER: scopus
PMCID: PMC2858911
DOI/URL:
Notes: --- - "Cited By (since 1996): 4" - "Export Date: 20 April 2011" - "CODEN: DEVPE" - "Source: Scopus"
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  1. Yulan Cheng
    2 Cheng
  2. Alexandra L Joyner
    98 Joyner
  3. Daniel N Stephen
    14 Stephen