Engrailed homeobox genes regulate establishment of the cerebellar afferent circuit map Journal Article
| Authors: | Sillitoe, R. V.; Vogel, M. W.; Joyner, A. L. |
| Article Title: | Engrailed homeobox genes regulate establishment of the cerebellar afferent circuit map |
| Abstract: | The spatial organization of the cerebellar afferent map has remarkable correspondence to two aspects of intrinsic patterning within the cerebellum embodied by a series of lobules and Purkinje cell (PC)-striped gene expression. Using male and female mice, we tested whether the Engrailed (En) homeobox genes are a common genetic substrate regulating all three systems, since they are expressed in spatially restricted domains within the cerebellum and are critical for patterning PC gene expression and foliation. Indeed, we discovered that En1/2 are necessary for the precise targeting of mossy fibers to distinct lobules, as well as their subsequent resolution into discrete parasagittal bands. Moreover, each En gene coordinately regulates afferent targeting and the striped pattern of PC protein expression (e.g., ZebrinII/AldolaseC) independent of regulating foliation. We further found that En1/2, rather than the presence of a full complement of lobules, are critical for generating PC protein stripes and mossy fiber bands, and that PC striped gene expression is determined before afferent banding. Thus, the En transcription factors not only regulate cerebellum circuit topography, but they also link afferent and efferent neurons precisely enough that alterations in PC protein expression can be used as a read out for underlying defects in circuitry. In summary, our data suggest that En1/2 are master regulators of three-dimensional organization of the cerebellum and coordinately regulate morphology, patterned gene expression, and afferent topography. Copyright © 2010 the authors. |
| Keywords: | controlled study; protein expression; unclassified drug; mutation; nonhuman; mouse; animals; mice; mice, knockout; animal tissue; cerebellum; purkinje cell; gene expression; neoplasm proteins; cell protein; animal experiment; nerve tissue proteins; homeodomain proteins; mice, inbred c57bl; transcription factors; gene expression regulation, developmental; kruppel-like transcription factors; gene control; homeodomain protein; brain mapping; brain region; axons; nerve net; cerebellar cortex; fructose bisphosphate aldolase; protein en 1; protein en 2; efferent nerve; mossy fiber; topography; heat-shock proteins; nerve fibers; wheat germ agglutinin-horseradish peroxidase conjugate |
| Journal Title: | The Journal of Neuroscience |
| Volume: | 30 |
| Issue: | 30 |
| ISSN: | 0270-6474 |
| Publisher: | Society for Neuroscience |
| Date Published: | 2010-07-28 |
| Start Page: | 10015 |
| End Page: | 10024 |
| Language: | English |
| DOI: | 10.1523/jneurosci.0653-10.2010 |
| PUBMED: | 20668186 |
| PROVIDER: | scopus |
| PMCID: | PMC2921890 |
| DOI/URL: | |
| Notes: | --- - "Export Date: 20 April 2011" - "CODEN: JNRSD" - "Source: Scopus" |
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