Engrailed homeobox genes determine the organization of Purkinje cell sagittal stripe gene expression in the adult cerebellum Journal Article
| Authors: | Sillitoe, R. V.; Stephen, D.; Lao, Z.; Joyner, A. L. |
| Article Title: | Engrailed homeobox genes determine the organization of Purkinje cell sagittal stripe gene expression in the adult cerebellum |
| Abstract: | Underlying the seemingly uniform cellular composition of the adult mammalian cerebellum (Cb) are striking parasagittal stripes of gene expression along the medial-lateral (ML) axis that are organized with respect to the lobules that divide the Cbalong the anterior-posterior (AP) axis. Although there is a clear correlation between the organization of gene expression stripes and Cb activity patterns, little is known about the genetic pathways that determine the intrinsic stripe molecular code. Here we establish that ML molecular code patterning is highly dependent on two homeobox transcription factors, Engrailed1 (En1) and En2, both of which are also required for patterning the lobules. Gene expression analysis of an allelic series of En1/2 mutant mice that have an intact Purkinje cell layer revealed severe patterning defects using three known components of the ML molecular code and a new marker of Hsp25 negative stripes (Neurofilament heavy chain, Nfh). Importantly, the complementary expression of ZebrinII/PhospholipaseCβ4 and Hsp25/Nfh changes in unison in each mutant. Furthermore, each En gene has unique as well as overlapping functions in patterning the ML molecular code and each En protein has dominant functions in different AP domains (subsets of lobules). Remarkably, in En1/2 mutants with almost normal foliation, ML molecular code patterning is severely disrupted. Thus, independent mechanisms that use En1/2 must pattern foliation and spatial gene expression separately. Our studies reveal that En1/2 are fundamental components of the genetic pathways that pattern the two intersecting coordinate systems of the Cb, morphological divisions and the molecular code. Copyright © 2008 Society for Neuroscience. |
| Keywords: | controlled study; protein expression; unclassified drug; nonhuman; protein function; animal cell; mouse; animals; mice; mice, knockout; cerebellum; purkinje cell; purkinje cells; gene expression; neoplasm proteins; nerve tissue proteins; transcription factor; homeodomain proteins; gene expression regulation, developmental; brain development; homeodomain protein; animals, newborn; gene dosage; brain mapping; body patterning; molecular code; patterning; zebrinii; phospholipase c beta; neurofilament protein; neurofilament proteins; heat-shock proteins; coordinate systems; en1; foliation; heat shock protein 25; phospholipase c beta4; protein nfh; transcription factor engrailed1; transcription factor engrailed2 |
| Journal Title: | The Journal of Neuroscience |
| Volume: | 28 |
| Issue: | 47 |
| ISSN: | 0270-6474 |
| Publisher: | Society for Neuroscience |
| Date Published: | 2008-11-19 |
| Start Page: | 12150 |
| End Page: | 12162 |
| Language: | English |
| DOI: | 10.1523/jneurosci.2059-08.2008 |
| PUBMED: | 19020009 |
| PROVIDER: | scopus |
| PMCID: | PMC2864318 |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 10" - "Export Date: 17 November 2011" - "CODEN: JNRSD" - "Source: Scopus" |
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