PMID- 19150487 OWN - NLM STAT- MEDLINE DCOM- 20091019 LR - 20211020 IS - 1873-7544 (Electronic) IS - 0306-4522 (Print) IS - 0306-4522 (Linking) VI - 162 IP - 3 DP - 2009 Sep 1 TI - Embryonic origins of ZebrinII parasagittal stripes and establishment of topographic Purkinje cell projections. PG - 574-88 LID - 10.1016/j.neuroscience.2008.12.025 [doi] AB - 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. FAU - Sillitoe, R V AU - Sillitoe RV AD - Developmental Biology Program, Sloan-Kettering Institute, 1275 York Avenue, New York, NY 10021, USA. FAU - Gopal, N AU - Gopal N FAU - Joyner, A L AU - Joyner AL LA - eng GR - R01 CA128158/CA/NCI NIH HHS/United States GR - AS1658/AS/Autism Speaks/United States GR - R01 HD035768/HD/NICHD NIH HHS/United States GR - R01 HD035768-10/HD/NICHD NIH HHS/United States GR - R01 MH085726/MH/NIMH NIH HHS/United States GR - R01 MH085726-01/MH/NIMH NIH HHS/United States GR - R01 CA128158-11/CA/NCI NIH HHS/United States GR - R01 HD035768-11/HD/NICHD NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20081224 PL - United States TA - Neuroscience JT - Neuroscience JID - 7605074 RN - 0 (DNA-Binding Proteins) RN - 0 (Guanine Nucleotide Exchange Factors) RN - 0 (Nerve Tissue Proteins) RN - 0 (Neuropeptides) RN - 0 (Pcp2 protein, mouse) RN - 0 (T-Box Domain Proteins) RN - 0 (Tbr1 protein, mouse) RN - 0 (zebrin II) RN - 147336-22-9 (Green Fluorescent Proteins) RN - EC 3.1.3.1 (Alkaline Phosphatase) RN - EC 3.1.4.11 (Phospholipase C beta) SB - IM MH - Alkaline Phosphatase/genetics MH - Animals MH - Animals, Newborn MH - Axons/metabolism MH - Body Patterning/genetics/*physiology MH - Brain Mapping MH - Cerebellar Nuclei/cytology MH - Cerebellum/*cytology/embryology MH - DNA-Binding Proteins/metabolism MH - Embryo, Mammalian MH - Functional Laterality MH - Gene Expression Regulation, Developmental/genetics/*physiology MH - Green Fluorescent Proteins/genetics MH - Guanine Nucleotide Exchange Factors/genetics/metabolism MH - Humans MH - Mice MH - Mice, Transgenic MH - Nerve Tissue Proteins/*metabolism MH - Neural Pathways/metabolism MH - Neuropeptides/genetics/metabolism MH - Phospholipase C beta/metabolism MH - Purkinje Cells/cytology/*physiology MH - T-Box Domain Proteins PMC - PMC2716412 MID - NIHMS84789 EDAT- 2009/01/20 09:00 MHDA- 2009/10/20 06:00 PMCR- 2010/09/01 CRDT- 2009/01/20 09:00 PHST- 2008/10/31 00:00 [received] PHST- 2008/12/15 00:00 [revised] PHST- 2008/12/15 00:00 [accepted] PHST- 2009/01/20 09:00 [entrez] PHST- 2009/01/20 09:00 [pubmed] PHST- 2009/10/20 06:00 [medline] PHST- 2010/09/01 00:00 [pmc-release] AID - S0306-4522(08)01796-X [pii] AID - 10.1016/j.neuroscience.2008.12.025 [doi] PST - ppublish SO - Neuroscience. 2009 Sep 1;162(3):574-88. doi: 10.1016/j.neuroscience.2008.12.025. Epub 2008 Dec 24.