Department of Ophthalmology and Visual Science, Yale University School of Medicine, New Haven, CT 06511, USA.
Department of Cellular and Molecular Physiology, Yale University School of Medicine, New Haven, CT 06511, USA.
Development. 2019 Jul 22;146(14):dev171926. doi: 10.1242/dev.171926.
Developmental control of long-range neuronal connections in the mammalian midbrain remains unclear. We explored the mechanisms regulating target selection of the developing superior colliculus (SC). The SC is a midbrain center that directs orienting behaviors and defense responses. We discovered that a transcription factor, Rorβ, controls establishment of axonal projections from the SC to two thalamic nuclei: the dorsal lateral geniculate nucleus (dLGN) and the lateral posterior nucleus (LP). A genetic strategy used to visualize SC circuits revealed that in control animals Rorβ neurons abundantly innervate the dLGN but barely innervate the LP. The opposite phenotype was observed in global and conditional mutants: projections to the dLGN were strongly decreased, and projections to the LP were increased. Furthermore, overexpression of in the wild type showed increased projections to the dLGN and decreased projections to the LP. In summary, we identified Rorβ as a key developmental mediator of colliculo-thalamic innervation. Such regulation could represent a general mechanism orchestrating long-range neuronal connections in the mammalian brain.
哺乳动物中脑长程神经元连接的发育控制仍不清楚。我们探讨了调节发育中的上丘（SC）靶区选择的机制。SC 是一个中脑中枢，指导定向行为和防御反应。我们发现转录因子 Rorβ控制着来自 SC 的轴突投射到两个丘脑核：背外侧膝状体核（dLGN）和外侧后核（LP）。一种用于可视化 SC 回路的遗传策略表明，在对照动物中，Rorβ神经元大量支配 dLGN，但几乎不支配 LP。在全局和条件性突变体中观察到相反的表型：投射到 dLGN 的显著减少，投射到 LP 的增加。此外，在野生型中过表达 导致投射到 dLGN 的增加和投射到 LP 的减少。总之，我们确定 Rorβ 是丘系-丘脑投射发育的关键发育介质。这种调节可能代表了一种在哺乳动物大脑中协调长程神经元连接的普遍机制。
