Embryonic origins of ZebrinII parasagittal stripes and establishment of topographic Purkinje cell projections Journal Article


Authors: Sillitoe, R. V.; Gopal, N.; Joyner, A. L.
Article Title: Embryonic origins of ZebrinII parasagittal stripes and establishment of topographic Purkinje cell projections
Abstract: The establishment of neural circuits involves both the precise positioning of cells within brain regions and projection of axons to specific target cells. In the cerebellum (Cb), the medial-lateral (M-L) and anterior-posterior (A-P) position of each Purkinje cell (PC) and the topography of its axon can be defined with respect to two coordinate systems within the Cb; one based on the pattern of lobules and the other on PC gene expression in parasagittal clusters in the embryo (e.g. Pcp2) and stripes in the adult (e.g. ZebrinII). The relationship between the embryonic clusters of molecularly defined PCs and particular adult PC stripes is not clear. Using a mouse genetic inducible fate mapping (GIFM) approach and a Pcp2-CreER-IRES-hAP transgene, we marked three bilateral clusters of PC clusters with myristolated green fluorescent protein (mGfp) on approximately embryonic day (E) 15 and followed their fate into adulthood. We found that these three clusters contributed specifically to ZebrinII-expressing PCs, including nine of the adult stripes. This result suggests that embryonic PCs maintain a particular molecular identity, and that each embryonic cluster can contribute PCs to more than one adult M-L stripe. Each PC projects a primary axon to one of the deep cerebellar nuclei (DCN) or the vestibular nuclei in the brainstem in an organized fashion that relates to the position of the PCs along the M-L axis. We characterized when PC axons from the three M-L clusters acquire topographic projections. Using a combination of GIFM to mark the PC clusters with mGfp and staining for human placental alkaline phosphatase (hAP) in Pcp2-CreER-IRES-hAP transgenic embryos we found that axons from each embryonic PC cluster intermingled with neurons within particular DCN or projected out of the Cb toward the vestibular nuclei by E14.5. These studies show that PC molecular patterning, efferent circuitry, and DCN nucleogenesis occur simultaneously, suggesting a link between these processes. © 2009 IBRO.
Keywords: controlled study; protein expression; unclassified drug; dna-binding proteins; nonhuman; mouse; animals; mice; animal tissue; cerebellum; purkinje cell; purkinje cells; green fluorescent protein; nerve tissue proteins; embryo development; embryo pattern formation; mice, transgenic; gene expression regulation, developmental; alkaline phosphatase; brain development; nerve fiber; transgene; green fluorescent proteins; embryo, mammalian; animals, newborn; brain mapping; functional laterality; neuropeptides; body patterning; axons; lyase; axon topography; deep nuclei; l7/pcp-2; molecular code; patterning; zebrinii; alkaline phosphatase placenta isoenzyme; zebrinii protein; cerebellum nucleus; nerve projection; vestibular nucleus; cerebellar nuclei; guanine nucleotide exchange factors; neural pathways; phospholipase c beta
Journal Title: Neuroscience
Volume: 162
Issue: 3
ISSN: 0306-4522
Publisher: Pergamon-Elsevier Science Ltd  
Date Published: 2009-09-01
Start Page: 574
End Page: 588
Language: English
DOI: 10.1016/j.neuroscience.2008.12.025
PUBMED: 19150487
PROVIDER: scopus
PMCID: PMC2716412
DOI/URL:
Notes: --- - "Cited By (since 1996): 3" - "Export Date: 30 November 2010" - "CODEN: NRSCD" - "Source: Scopus"
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  1. Alexandra L Joyner
    98 Joyner
  2. Nithya Gopal
    1 Gopal