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

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.

Pubmed ID: 19150487

Authors

  • Sillitoe RV
  • Gopal N
  • Joyner AL

Journal

Neuroscience

Publication Data

September 1, 2009

Associated Grants

  • Agency: Autism Speaks, Id: AS1658
  • Agency: NCI NIH HHS, Id: R01 CA128158
  • Agency: NCI NIH HHS, Id: R01 CA128158-11
  • Agency: NICHD NIH HHS, Id: R01 HD035768
  • Agency: NICHD NIH HHS, Id: R01 HD035768-10
  • Agency: NICHD NIH HHS, Id: R01 HD035768-11
  • Agency: NIMH NIH HHS, Id: R01 MH085726
  • Agency: NIMH NIH HHS, Id: R01 MH085726-01

Mesh Terms

  • Alkaline Phosphatase
  • Animals
  • Animals, Newborn
  • Axons
  • Body Patterning
  • Brain Mapping
  • Cerebellar Nuclei
  • Cerebellum
  • DNA-Binding Proteins
  • Embryo, Mammalian
  • Functional Laterality
  • Gene Expression Regulation, Developmental
  • Green Fluorescent Proteins
  • Guanine Nucleotide Exchange Factors
  • Humans
  • Mice
  • Mice, Transgenic
  • Nerve Tissue Proteins
  • Neural Pathways
  • Neuropeptides
  • Phospholipase C beta
  • Purkinje Cells