\nNeuroanatomists have long speculated that expanded primate brains contain an\nincreased morphological diversity of inhibitory neurons (doi:10.1038/nrn3444,\nDeFelipe et al.; Ramón y Cajal) and recent studies have identified\nprimate-specific neuronal populations at the molecular\nlevel(doi:10.1038/s41593-018-0205-2, Boldog et al.;\ndoi:10.1038/s41586-020-2781-z, Krienen et al.). However, we know little about\nthe developmental mechanisms that specify evolutionarily novel cell types in\nthe brain. Here, we reconstructed gene expression trajectories specifying\ninhibitory neurons spanning the neurogenic period in macaque and mouse by\nanalyzing the transcriptomes of 250,181 cells. We find that the initial classes\nof inhibitory neurons generated prenatally are largely conserved among mammals.\nNonetheless, we discover two contrasting developmental mechanisms for\nspecifying evolutionarily novel cell types during prenatal development. First,\nwe show that recently-identified primate-specific TAC3 striatal interneurons\nare specified by a unique transcriptional program in progenitors followed by\ninduction of a distinct suite of neuropeptides and neurotransmitter receptors\nin newborn neurons. Second, we find that multiple classes of\ntranscriptionally-conserved olfactory-bulb bound precursors are redirected to\nexpanded primate white matter and striatum, including a novel peristriatal\nclass, striatum laureatum neurons, that resemble dopaminergic periglomerular\ncells of the olfactory bulb. We propose an evolutionary “reduce and reuse”\nmodel of inhibitory neuron distribution that accounts for the unequal scaling\nof primate olfactory bulb, source progenitor domains, and cortical white\nmatter. Together, our results provide a unified developmental taxonomy of\ninitial classes of mammalian inhibitory neurons and reveal multiple\ndevelopmental mechanisms for neural cell type evolution.\n\n
\nThe datasets provided here include 10X Genomics single cell RNA-seq inhibitory\nneurons from the developing macaque, developing mouse and the adult mouse.\n\n
\nQualitative definitions of initial and terminal cell classes can be found in \nSupplementary Table 4 of Schmitz et al. Nature. 2022.\n", "methods": "\nDissociated whole cells from regions dissected from the developing macaque\ncerebrum run on 10X Genomics V2 and 3 3' capture scRNAseq. Reads were\nquantified using kallisto-bustools, ambient RNA removed using cellbender,\nfollowed by normalization, scaling and PCA. The KNN corrects for batch using\nBBKNN.\n", "paper_url": "https://www.nature.com/articles/s41586-022-04510-w Schmitz et al. Nature. 2022.", "pmid": "35322231", "geo_series": "GSE169122", "sra_study": "SRP311340", "bioproject": "PRJNA715715", "submitter": "Matthew Schmitz", "version": 1, "submission_date": "2021-09-15", "lab": "Alex Pollen Lab", "institution": "UCSF", "inDir": "/hive/data/inside/cells/datasets/dev-inhibitory-neurons" }