Center for Brain Science and Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138, USA.
Proc Natl Acad Sci U S A. 2012 Oct 23;109(43):17663-8. doi: 10.1073/pnas.1215806109. Epub 2012 Oct 8.
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.
光感受器、中间神经元（水平细胞、双极细胞和无长突细胞）、视网膜神经节细胞（RGCs）和神经胶质细胞。其中许多类型可以进一步分为多个在功能、结构和分子上不同的亚型（例如，RGCs 有~25 种亚型）。目前尚不清楚祖细胞何时以及如何决定产生这些亚型。在这里，我们确定了对垂直运动有选择性反应并表达钙粘蛋白 6（cdh6）的 RGC 的起源。通过基于 Cre 重组酶的谱系追踪，我们表明这些 RGC 来自本身表达 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，但它们产生的 RGC 主要是单方向选择性的亚型。相比之下，cdh6 阳性祖细胞仍然能够产生多种类型的无长突细胞和双极细胞。我们的结果表明，类型和亚型的特异性受到不同方式的调控，并表明多能但命运受限的祖细胞有助于视网膜中的亚型特异性。
