@article{98837f1ec6b54012817373cf7b3a6c8a,
title = "Proneural genes define ground-state rules to regulate neurogenic patterning and cortical folding",
abstract = "Asymmetric neuronal expansion is thought to drive evolutionary transitions between lissencephalic and gyrencephalic cerebral cortices. We report that Neurog2 and Ascl1 proneural genes together sustain neurogenic continuity and lissencephaly in rodent cortices. Using transgenic reporter mice and human cerebral organoids, we found that Neurog2 and Ascl1 expression defines a continuum of four lineage-biased neural progenitor cell (NPC) pools. Double+ NPCs, at the hierarchical apex, are least lineage restricted due to Neurog2-Ascl1 cross-repression and display unique features of multipotency (more open chromatin, complex gene regulatory network, G2 pausing). Strikingly, selectively eliminating double+ NPCs by crossing Neurog2-Ascl1 split-Cre mice with diphtheria toxin-dependent “deleter” strains locally disrupts Notch signaling, perturbs neurogenic symmetry, and triggers cortical folding. In support of our discovery that double+ NPCs are Notch-ligand-expressing “niche” cells that control neurogenic periodicity and cortical folding, NEUROG2, ASCL1, and HES1 transcript distribution is modular (adjacent high/low zones) in gyrencephalic macaque cortices, prefiguring future folds.",
keywords = "cortical folding, epigenome, gene regulatory network, lineage priming, neocortex, neural lineages, neural progenitor cells, Notch signaling, proneural genes, transcriptome",
author = "Sisu Han and Satoshi Okawa and Wilkinson, {Grey Atteridge} and Hussein Ghazale and Lata Adnani and Rajiv Dixit and Ligia Tavares and Imrul Faisal and Brooks, {Matthew J.} and Veronique Cortay and Dawn Zinyk and Adam Sivitilli and Saiqun Li and Faizan Malik and Yaroslav Ilnytskyy and Angarica, {Vladimir Espinosa} and Jinghua Gao and Vorapin Chinchalongporn and Oproescu, {Ana Maria} and Lakshmy Vasan and Yacine Touahri and David, {Luke Ajay} and Eko Raharjo and Kim, {Jung Woong} and Wei Wu and Waleed Rahmani and Chan, {Jennifer Ai wen} and Igor Kovalchuk and Liliana Attisano and Deborah Kurrasch and Colette Dehay and Anand Swaroop and Castro, {Diogo S.} and Jeff Biernaskie and {del Sol}, Antonio and Carol Schuurmans",
note = "Funding Information: We thank Marjorie Brand, Magdalena Gӧtz, and Fran{\c c}ois Guillemot for critical comments and Petia Stefanova, Yutaka Amemiya (SRI), Andrey Golubov (U of Lethbridge), and Ying Liu (Applied Organoid Core, U of T) for technical help. This work was supported by a Canadian Institutes of Health Research (CIHR PJT – 162108 ) operating grant to C.S. and I.K., Canada-Israel Health Research Initiative (jointly funded by CIHR, Israel Science Foundation, International Development Research Centre, Azrieli Foundation; IDRC 108875 ) to C.S., FCT grant PTDC/BIA-BID/29663/2017 to D.S.C., Intramural Research Program of the National Eye Institute , NIH ( ZIAEY000450 ) to A. Swaroop, and Krembil Foundation and Canada First Research Excellence Fund /Medicine by Design to L. Attisano. C.S. holds the Dixon Family Chair in Ophthalmology Research, and J.B. holds the Calgary Firefighters Burn Treatment Society Chair in Skin Regeneration and Wound Healing. S.H. was supported by scholarships from the Cumming School of Medicine , Ontario Government Scholarship, UofT Vision Science Research Program, Peterborough K.M. HUNTER Charitable Foundation , and Margaret and Howard GAMBLE Research Grant; G.A.W. by Frederick Banting and Charles Best Canada, Alberta Innovates Health Solutions , and ACHRI/CIHR Training grant; S.O. by a FNR CORE grant ( C15/BM/10397420 ); R.D. by a CIHR Canada HOPE Fellowship, and L. Adnani by an ACHRI/CIHR Training Grant. Funding Information: We thank Marjorie Brand, Magdalena G?tz, and Fran?ois Guillemot for critical comments and Petia Stefanova, Yutaka Amemiya (SRI), Andrey Golubov (U of Lethbridge), and Ying Liu (Applied Organoid Core, U of T) for technical help. This work was supported by a Canadian Institutes of Health Research (CIHR PJT ? 162108) operating grant to C.S. and I.K. Canada-Israel Health Research Initiative (jointly funded by CIHR, Israel Science Foundation, International Development Research Centre, Azrieli Foundation; IDRC 108875) to C.S. FCT grant PTDC/BIA-BID/29663/2017 to D.S.C. Intramural Research Program of the National Eye Institute, NIH (ZIAEY000450) to A. Swaroop, and Krembil Foundation and Canada First Research Excellence Fund/Medicine by Design to L. Attisano. C.S. holds the Dixon Family Chair in Ophthalmology Research, and J.B. holds the Calgary Firefighters Burn Treatment Society Chair in Skin Regeneration and Wound Healing. S.H. was supported by scholarships from the Cumming School of Medicine, Ontario Government Scholarship, UofT Vision Science Research Program, Peterborough K.M. HUNTER Charitable Foundation, and Margaret and Howard GAMBLE Research Grant; G.A.W. by Frederick Banting and Charles Best Canada, Alberta Innovates Health Solutions, and ACHRI/CIHR Training grant; S.O. by a FNR CORE grant (C15/BM/10397420); R.D. by a CIHR Canada HOPE Fellowship, and L. Adnani by an ACHRI/CIHR Training Grant. Conceptualization, formal analysis, investigation, methodology, visualization, validation, writing ? original draft, writing ? review & editing, S.H. and G.A.W.; formal analysis, investigation, writing ? review & editing, H.G. L. Adnani, R.D. L.T. I.F. V. Cortay, D.Z. A. Sivitilli, S.L. F.M. J.G. V. Chinchalongporn, A.-M.O. L.V. Y.T. L.A.D. E.R. J.-W.K. W.W. and W.R.; formal analysis, methodology, software, investigation, writing ? review & editing, S.O. M.J.B. Y.I. and V.E.A.; validation, writing ? original draft; writing ? review & editing, J.A.C. I.K. L. Attisano, D.K. C.D. A. Swaroop, D.S.C. J.B. and A.d.S.; funding acquisition, conceptualization, project administration, resources, supervision, validation, writing ? original draft; writing ? review & editing, C.S. The authors declare no conflicts of interest. Publisher Copyright: {\textcopyright} 2021 Elsevier Inc.",
year = "2021",
month = sep,
day = "15",
doi = "10.1016/j.neuron.2021.07.007",
language = "English",
volume = "109",
pages = "2847--2863.e11",
journal = "Neuron",
issn = "0896-6273",
publisher = "Cell Press",
number = "18",
}