Fralin Biomedical Research Institute at Virginia Tech Carilion, Roanoke, Virginia, USA.
School of Neuroscience, College of Science, Virginia Tech, Blacksburg, Virginia, USA.
J Comp Neurol. 2024 Mar;532(3):e25606. doi: 10.1002/cne.25606.
The mouse retina contains over 40 types of retinal ganglion cells (RGCs) that differ in morphology, function, or gene expression. RGCs also differ by whether their axons target the brain.s ipsilateral or contralateral hemisphere. Contralaterally projecting RGCs (contraRGCs) are widespread in mouse retina, whereas ipsilateral projecting RGCs (ipsiRGCs) are confined to the ventro-temporal (VT) crescent of retina. In this study, we employed the Sert-Cre transgenic line, which had been reported to selectively label ipsiRGCs, to study ipsiRGCs during development. Although the number of Cre-expressing ipsiRGCs did not significantly increase with postnatal age, the region of retina that they occupied did, and by adulthood represented ~30% of the retinal surface. Unexpectedly, genetic ablation of Sert-Cre cells failed to fully disrupt ipsilateral projecting retinal axons, suggesting that not all ipsiRGCs generated Cre in Sert-Cre mice. To test this hypothesis, we retrogradely labeled ipsiRGCs in Sert-Cre mice which revealed that not all ipsiRGCs are labeled in Sert-Cre mice and a small population of contraRGCs flanking the VT crescent generates Cre in this line. These results do not negate the usefulness of the Sert-Cre mouse but do raise important caveats to the interpretation of such studies.
鼠标视网膜包含超过 40 种视网膜神经节细胞 (RGCs)，它们在形态、功能或基因表达上有所不同。RGCs 的轴突也因其靶向大脑的同侧或对侧半球而有所不同。对侧投射的 RGCs（contraRGCs）在鼠标视网膜中广泛存在，而同侧投射的 RGCs（ipsiRGCs）则局限于视网膜的腹侧颞部（VT）新月形区域。在这项研究中，我们使用了 Sert-Cre 转基因系，该系已被报道可选择性标记 ipsiRGCs，以研究发育过程中的 ipsiRGCs。尽管表达 Cre 的 ipsiRGCs 的数量并没有随着出生后年龄的增加而显著增加，但它们占据的视网膜区域却增加了，到成年时占视网膜表面积的~30%。出乎意料的是，Sert-Cre 细胞的遗传消融未能完全破坏同侧投射的视网膜轴突，这表明并非所有 ipsiRGCs 在 Sert-Cre 小鼠中都产生 Cre。为了验证这一假设，我们在 Sert-Cre 小鼠中逆行标记 ipsiRGCs，结果表明并非所有 ipsiRGCs 在 Sert-Cre 小鼠中都被标记，而 VT 新月形区域周围的一小部分 contraRGCs 在这条线中产生 Cre。这些结果并没有否定 Sert-Cre 小鼠的有用性，但确实对这类研究的解释提出了重要的警告。
