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Genetic and epigenetic coordination of cortical interneuron development

Allaway, Kathryn C ; Gabitto, Mariano I ; Wapinski, Orly ; Saldi, Giuseppe ; Wang, Chen-Yu ; Bandler, Rachel C ; Wu, Sherry Jingjing ; Bonneau, Richard ; Fishell, Gord

Nature (London), 2021-09, Vol.597 (7878), p.693-697 [Periódico revisado por pares]

England: Nature Publishing Group

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Título:
Genetic and epigenetic coordination of cortical interneuron development
Autor: Allaway, Kathryn C ; Gabitto, Mariano I ; Wapinski, Orly ; Saldi, Giuseppe ; Wang, Chen-Yu ; Bandler, Rachel C ; Wu, Sherry Jingjing ; Bonneau, Richard ; Fishell, Gord
Assuntos: Animals ; Cell cycle ; Cell Differentiation ; Cell Movement ; Cerebral cortex ; Cerebral Cortex - cytology ; Chromatin ; Datasets ; Epigenesis, Genetic ; Epigenetic inheritance ; Epigenetics ; Female ; Gene expression ; Gene Regulatory Networks ; Genetic aspects ; Interneurons ; Interneurons - cytology ; Investigations ; Male ; MEF2 Transcription Factors - genetics ; Mice ; Mice, Knockout ; Neurogenesis ; Observations ; Parvalbumin ; Parvalbumins - metabolism ; RNA-Seq ; Single-Cell Analysis ; Somatostatin ; Somatostatin - metabolism ; Transcription ; Transcription factors
É parte de: Nature (London), 2021-09, Vol.597 (7878), p.693-697
Notas: ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
Co-first authors; these authors are listed alphabetically and their specific contributions are detailed in the author contributions.
Author Contributions
K.C.A., M.I.G., O.W., R.B., and G.F. conceived the original project. K.C.A led experimental work, with assistance from O.W., C.W., R.C.B., and S.J.W., and supervised by G.F. M.I.G. led computational analysis, assisted by G.S. and K.C.A., and supervised by R.B. K.C.A., M.I.G., G.S., R.B., and G.F. interpreted the data and wrote the manuscript, with input from O.W. and C.W.
Descrição: One of the hallmarks of the cerebral cortex is the extreme diversity of interneurons . The two largest subtypes of cortical interneurons, parvalbumin- and somatostatin-positive cells, are morphologically and functionally distinct in adulthood but arise from common lineages within the medial ganglionic eminence . This makes them an attractive model for studying the generation of cell diversity. Here we examine how developmental changes in transcription and chromatin structure enable these cells to acquire distinct identities in the mouse cortex. Generic interneuron features are first detected upon cell cycle exit through the opening of chromatin at distal elements. By constructing cell-type-specific gene regulatory networks, we observed that parvalbumin- and somatostatin-positive cells initiate distinct programs upon settling within the cortex. We used these networks to model the differential transcriptional requirement of a shared regulator, Mef2c, and confirmed the accuracy of our predictions through experimental loss-of-function experiments. We therefore reveal how a common molecular program diverges to enable these neuronal subtypes to acquire highly specialized properties by adulthood. Our methods provide a framework for examining the emergence of cellular diversity, as well as for quantifying and predicting the effect of candidate genes on cell-type-specific development.
Editor: England: Nature Publishing Group
Idioma: Inglês

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Genetic and epigenetic coordination of cortical interneuron development

Allaway, Kathryn C ; Gabitto, Mariano I ; Wapinski, Orly ; Saldi, Giuseppe ; Wang, Chen-Yu ; Bandler, Rachel C ; Wu, Sherry Jingjing ; Bonneau, Richard ; Fishell, Gord

England: Nature Publishing Group

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