André Sousa, PhD – Slide of the Week

André Sousa, PhD - Slide of the Week

Title: Species- and cell type-specific expression of the neuropsychiatric risk gene FOXP2

Legend: A) Violin plots of FOXP2 expression across all subclasses in the four primates and mouse neocortex. B) Immunofluorescent staining against IBA1 (red) combined with RNA in situ hybridization for FOXP2 (green) in L6 of human dlPFC. Arrowheads indicate FOXP2+/IBA1+ microglia, whereas the arrow indicates FOXP2-/IBA1+ microglia. The pie chart summarizes the proportion of FOXP2-expressing cells among IBA1-immunopositive cells. C) Representative images of FOXP2 immunohisto- chemistry throughout cortical columns in human, chimpanzee, mouse, and echidna. The position of layers and white matter (WM) are indicated. Insets for echidna highlight numerous FOXP2-immunopositive nuclei in the striatum and scarce FOXP2-immunopositive nuclei in the deep neocortical layers. D) Phylogenetic dendrogram of the 51 mammals and their corresponding laminar distribution of FOXP2-immunopositive nuclei.

Citation: Ma S*, Skarica M*, Li Q, Xu C, Risgaard RD, Tebbenkamp ATN, Mato-Blanco X, Kovner R,  Krsnik Z, de Martin X, Luria V, Martí-Pérez X, Liang D, Karger A, Schmidt DK, Gomez-Sanchez Z, Qi C, Gobeske KT, Pochareddy S, Debnath A, Hottman CJ, Spurrier J, Teo L, Boghdadi AG, Homman-Ludiye J, Ely JJ, Daadi EW, Mi D, Daadi M, Marín O, Hof PR, Rasin M-R, Bourne J, Sherwood CC, Santpere G, Girgenti MJ, Strittmatter SM#, Sousa AMM#, Sestan N#. (2022) Molecular and cellular evolution of the primate dorsolateral prefrontal cortex. Science 377, abo7257. (*co-first author; # corresponding author)

Abstract: The granular dorsolateral prefrontal cortex (dlPFC) is an evolutionary specialization of primates that is centrally involved in cognition. We assessed more than 600,000 single-nucleus transcriptomes from adult human, chimpanzee, macaque, and marmoset dlPFC. Although most cell subtypes defined transcriptomically are conserved, we detected several that exist only in a subset of species as well as substantial species-specific molecular differences across homologous neuronal, glial, and non-neural subtypes. The latter are exemplified by human-specific switching between expression of the neuropeptide somatostatin and tyrosine hydroxylase, the rate-limiting enzyme in dopamine production in certain interneurons. The above molecular differences are also illustrated by expression of the neuropsychiatric risk gene FOXP2, which is human-specific in microglia and primate-specific in layer 4 granular neurons. We generated a comprehensive survey of the dlPFC cellular repertoire and its shared and divergent features in anthropoid primates.

About the Lab: The Sousa lab aims to identify and characterize the molecular and cellular mechanisms that govern human brain development and evolution, and to apply that knowledge towards understanding neurodevelopmental and psychiatric disorders.

Investigator: André Sousa, PhD

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