Molecular programs of regional specification and neural stem cell fate progression in macaque telencephalon.

During early telencephalic development, intricate processes of regional patterning and neural stem cell (NSC) fate specification take place. However, our understanding of these processes in primates, including both conserved and species-specific features, remains limited. Here, we profiled 761,529 single-cell transcriptomes from multiple regions of the prenatal macaque telencephalon. We deciphered the molecular programs of the early organizing centers and their cross-talk with NSCs, revealing primate-biased galanin-like peptide (GALP) signaling in the anteroventral telencephalon. Regional transcriptomic variations were observed along the frontotemporal axis during early stages of neocortical NSC progression and in neurons and astrocytes. Additionally, we found that genes associated with neuropsychiatric disorders and brain cancer risk might play critical roles in the early telencephalic organizers and during NSC progression.

MicroRNA-19b restricts Wnt7b to the hem, which induces aspects of hippocampus development in the avian forebrain.

The functions of the hippocampus are conserved between birds and mammals; however, it is not known whether similar mechanisms are responsible for its development in these two classes. In mammals, hippocampus development is known to be regulated by the hem organizer. Here, we have identified that, in birds, Wnt7b secreted from the hem is sufficient for inducing the expression of hippocampal markers. Furthermore, we have demonstrated that a microRNA, miR-19b, which is selectively excluded from the hem region, is necessary and sufficient for restricting the expression of Wnt7b to the hem. This study suggests that the role of the Wnt signal emanating from the hem is conserved between birds and mammals, and that a microRNA-based mechanism is crucial for determining the position of the hippocampus.