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Title

Temporal controls over inter-areal cortical projection neuron fate diversity

Authors
Kebschull, Justus M
Santinha, Antonio
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Published in Nature. 2021, vol. 599, no. 7885, p. 453-457
Abstract

Interconnectivity between neocortical areas is critical for sensory integration and sensorimotor transformations1-6. These functions are mediated by heterogeneous inter-areal cortical projection neurons (ICPN), which send axon branches across cortical areas as well as to subcortical targets7-9. Although ICPN are anatomically diverse10-14, they are molecularly homogeneous15, and how the diversity of their anatomical and functional features emerge during development remains largely unknown. Here we address this question by linking the connectome and transcriptome in developing single ICPN of the mouse neocortex using a combination of multiplexed analysis of projections by sequencing16,17(MAPseq, to identify single-neuron axonal projections) and single-cell RNA sequencing (to identify corresponding gene expression). Focusing on neurons of the primary somatosensory cortex (S1), we reveal a protracted unfolding of the molecular and functional differentiation of motor cortex-projecting (M) ICPN compared with secondary somatosensory cortex-projecting (S2) ICPN. We identify SOX11 as a temporally differentially expressed transcription factor in M versus S2 ICPN. Postnatal manipulation of SOX11 expression in S1 impaired sensorimotor connectivity and disrupted selective exploratory behaviours in mice. Together, our results reveal that within a single cortical area, different subtypes of ICPN have distinct postnatal paces of molecular differentiation, which are subsequently reflected in distinct circuit connectivities and functions. Dynamic differences in the expression levels of a largely generic set of genes, rather than fundamental differences in the identity of developmental genetic programs, may thus account for the emergence of intra-type diversity in cortical neurons.

Keywords Cell DifferentiationConnectomeNeural PathwaysTranscriptome
Identifiers
PMID: 34754107
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Dataset: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE118681
Dataset: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE116944
Dataset: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE156080
Structures
Research groups Neurobiologie développementale et plasticité (880)
Les dysfonctions synaptiques du cerveau (971)
Groupe Dayer Alexandre (Formation du circuit cortical) (875)
NCCR Synapsy
Projects
Swiss National Science Foundation: 51NF40-185897
Swiss National Science Foundation: 51NF40-158776
Swiss National Science Foundation: 31003A_182326
Citation
(ISO format)
KLINGLER, Esther et al. Temporal controls over inter-areal cortical projection neuron fate diversity. In: Nature, 2021, vol. 599, n° 7885, p. 453-457. doi: 10.1038/s41586-021-04048-3 https://archive-ouverte.unige.ch/unige:163454

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Deposited on : 2022-09-21

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