In the mature brain, functionally distinct areas connect to specific targets, mediating network activity required for function. New insights are still occurring regarding how specific connectivity occurs in the developing brain. Decades of work have revealed important insights into the molecular and genetic mechanisms regulating cell type specification in the brain. This work classified long-range projection neurons of the cerebral cortex into three major classes based on their primary target (e.g. subcortical, intracortical, and interhemispheric projections). However, painstaking single-cell mapping reveals that long-range projection neurons of the corpus callosum connect to multiple and overlapping ipsilateral and contralateral targets with often highly branched axons. In addition, their scRNA transcriptomes are highly variable, making it difficult to identify meaningful subclasses. This work has prompted us to reexamine how cortical projection neurons that comprise the corpus callosum are currently classified and how this stunning array of variability might be achieved during development.

在成熟的大脑中，功能不同的区域连接到特定的目标，调节功能所需的网络活动。关于发育中的大脑中特定连接如何发生的新见解仍在不断出现。数十年的工作揭示了对调节大脑细胞类型规范的分子和遗传机制的重要见解。这项工作根据其主要目标（例如皮质下、皮质内和半球间投射）将大脑皮层的远程投射神经元分为三大类。然而，艰苦的单细胞绘图表明，胼胝体的远程投射神经元连接到多个重叠的同侧和对侧目标，这些目标通常具有高度分支的轴突。此外，它们的scRNA转录组变化很大，因此很难识别有意义的亚类。这项工作促使我们重新审视构成胼胝体的皮质投射神经元目前是如何分类的，以及在发育过程中如何实现这种令人惊叹的变异性。