Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 109, Issue 43, Pages 17663-17668Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1215806109
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Funding
- National Institutes of Health [NS29169, EY019355]
- National Science and Engineering Research Council of Canada grant
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Single progenitors can give rise to any and all of the main retinal cell types: photoreceptors, interneurons (horizontal, bipolar, and amacrine cells), retinal ganglion cells (RGCs), and glia. Many of these types are divisible into multiple functionally, structurally, and molecularly distinct subtypes (e. g., similar to 25 for RGCs). It remains unknown when and how progenitors become committed to generate such subtypes. Here, we determine the origin of RGCs that respond selectively to vertical motion and express cadherin 6 (cdh6). Using Cre recombinase-based lineage tracing, we show that these RGCs arise from progenitors that themselves express cdh6. These progenitors are capable of generating all major retinal cell types, but the RGCs they generate are predominantly of the single direction-selective subtype. In contrast, cdh6-positive progenitors retain the ability to generate multiple subtypes of amacrine and bipolar cells. Our results demonstrate that type and subtype specification are regulated in different ways and suggest that multipotential but fate-restricted progenitors contribute to subtype specification in retina.
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