SRA

Neuroanatomists have long speculated that expanded primate brains contain an increased morphological diversity of inhibitory neurons (doi:10.1038/nrn3444, DeFelipe et al.) and recent studies have identified primate-specific neuronal populations at the molecular level(doi:10.1038/s41586-020-2781-z, Krienen et al.). However, we know little about the developmental mechanisms that specify evolutionarily novel cell types in the brain. Here, we reconstructed gene expression trajectories specifying inhibitory neurons spanning the neurogenic period in macaque and mouse by analyzing the transcriptomes of 250,181 cells. We find that the initial classes of inhibitory neurons generated prenatally are largely conserved among mammals. Nonetheless, we identify two contrasting developmental mechanisms for specifying evolutionarily novel cell types during prenatal development. First, we show that recently-identified primate-specific TAC3 striatal interneurons are specified by a unique transcriptional program in progenitors followed by induction of a distinct suite of neuropeptides and neurotransmitter receptors in newborn neurons. Second, we find that multiple classes of transcriptionally-conserved olfactory-bulb bound precursors are redirected to expanded primate white matter and striatum, including a novel peristriatal class, striatum laureatum neurons, that resemble dopaminergic periglomerular cells of the olfactory bulb. We propose an evolutionary model in which conserved initial classes of neurons supplying the smaller primate olfactory bulb are reused in the enlarged striatum and cortex. Together, our results provide a unified developmental taxonomy of initial classes of mammalian inhibitory neurons and reveal multiple developmental mechanisms for neural cell type evolution. Overall design: 10X Genomics Chromium single cell 3' capture RNA-sequencing of 9 macaque embryos between embryonic day 40 and 100