| First Author | Nelson BR | Year | 2011 |
| Journal | PLoS One | Volume | 6 |
| Issue | 8 | Pages | e22817 |
| PubMed ID | 21829655 | Mgi Jnum | J:177592 |
| Mgi Id | MGI:5295528 | Doi | 10.1371/journal.pone.0022817 |
| Citation | Nelson BR, et al. (2011) Genome-wide analysis of Muller glial differentiation reveals a requirement for Notch signaling in postmitotic cells to maintain the glial fate. PLoS One 6(8):e22817 |
| abstractText | Previous studies have shown that Muller glia are closely related to retinal progenitors; these two cell types express many of the same genes and after damage to the retina, Muller glia can serve as a source for new neurons, particularly in non-mammalian vertebrates. We investigated the period of postnatal retinal development when progenitors are differentiating into Muller glia to better understand this transition. FACS purified retinal progenitors and Muller glia from various ages of Hes5-GFP mice were analyzed by Affymetrix cDNA microarrays. We found that genes known to be enriched/expressed by Muller glia steadily increase over the first three postnatal weeks, while genes associated with the mitotic cell cycle are rapidly downregulated from P0 to P7. Interestingly, progenitor genes not directly associated with the mitotic cell cycle, like the proneural genes Ascl1 and Neurog2, decline more slowly over the first 10-14 days of postnatal development, and there is a peak in Notch signaling several days after the presumptive Muller glia have been generated. To confirm that Notch signaling continues in the postmitotic Muller glia, we performed in situ hybridization, immunolocalization for the active form of Notch, and immunofluorescence for BrdU. Using genetic and pharmacological approaches, we found that sustained Notch signaling in the postmitotic Muller glia is necessary for their maturation and the stabilization of the glial identity for almost a week after the cells have exited the mitotic cell cycle. |
