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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Direction-selective retinal ganglion cells arise from molecularly specified multipotential progenitors
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Direction-selective retinal ganglion cells arise from molecularly specified multipotential progenitors

机译：方向选择性视网膜神经节细胞起源于分子指定的多能祖细胞

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摘要

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., ～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.
机译：单个祖细胞可以产生任何和所有主要的视网膜细胞类型：感光细胞，中间神经元（水平，双极和无长突细胞），视网膜神经节细胞（RGC）和神经胶质细胞。这些类型中的许多可分为多种功能，结构和分子上不同的亚型（例如，RGC约为25）。何时以及如何使祖细胞产生这种亚型仍是未知的。在这里，我们确定选择性响应垂直运动并表达钙粘蛋白6（cdh6）的RGC的起源。使用基于Cre重组酶的谱系追踪，我们显示这些RGC源自本身表达cdh6的祖细胞。这些祖细胞能够产生所有主要的视网膜细胞类型，但是它们产生的RGC主要是单向选择性亚型。相反，cdh6阳性祖细胞保留生成无长突细胞和双极细胞亚型的能力。我们的研究结果表明类型和亚型规范以不同的方式受到监管，并表明多能但受命运限制的祖细胞有助于视网膜中的亚型规范。

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    Irina De la Huerta; In-Jung Kim; P. Emanuela Voinescu; Joshua R. Sanes;

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    Center for Brain Science and Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138;

    Center for Brain Science and Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138,Department of Ophthalmology and Visual Science and Department of Neurobiology, Yale University School of Medicine, New Haven, CT 06511;

    Center for Brain Science and Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138;

    Center for Brain Science and Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138;

  • 收录信息 美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
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