Building the cerebral cortex: Cell and molecular mechanisms

Our team has made significant contributions on the role of cell cycle control in corticogenesis and the discovery of unique features of early primate development. We are one of the few groups that bridges the gap between the extensive work world-wide on the rodent-model of corticogenesis and the few labs able to work on human corticogenesis. Our work shows that the non human primate corticogenesis differs markedly form that in rodent and shares key features with the human primate.

We have established major differences in the nature and timing of the ontogenetic processes that characterize primate corticogenesis and were the first to identify a human and non-human primate-specific germinal zone: the Outer Sub Ventricular Zone (OSVZ) (Smart et al., 2002) . We have shown that the primate OSVZ includes a high diversity of progenitors including five morphotypes, each characterized by distinct proliferative behaviors. State transition analysis of a large database of lineage trees unexpectedly revealed frequent bidirectional transitions between progenitor types, not observed in other mammalian species (Betizeau et al., Neuron, 2013; Pfeiffer et al., J Comp Neurol, 2016).

We have discovered that primate-specific miRNA signatures uniquely distinguish VZ and OSVZ. Many of these primate-specific miRNAs target cell-cycle genes, indicating that each germinal zone has evolved its own cell-cycle regulation scheme. This suggests the evolution of a complex regulatory control system that may have contributed to the emergence of novel progenitor types interacting through complex lineages. (Arcila et al. Neuron, 2014; Dehay et al., Neuron, 2015)

One of major contributions include discovery of the role of cell-cycle regulation in establishing cortical architecture and cell lineage evolution, via control of cortical progenitor pool amplification and on mode of division (Pilaz et al., PNAS, 2009; Lukaszewicz et al., Neuron, 2005; Dehay and Kennedy, Nat Rev Neurosci, 2007). We have shown that a conserved mechanism, the asymmetrical spindle morphology (SSA) , known to be a core component of ACD in invertebrates is implicated in mammalian corticogenesis where it regulates cell-cycle exit and asymmetric division in apical progenitors of the VZ (Delaunay et al., 2014, Cell Reports, 2014; Delaunay et al., Curr Opin Neurobiol, 2017).

During the last decade, we have established the first line of rhesus ES cells, which we are currently using to generate 3D cortical organoids (Wianny et al., Stem Cells 2008; Stem Cell Res, 2016)

Year	Authors	Title	Journal
2020	Magrou L, Barone P, Markov NT, Scheeren G, Killackey HP, Giroud P, Berland M, Knoblauch K, Dehay C, Kennedy H, *co-senior authors	Unique Features of Subcortical Circuits in a Macaque Model of Congenital Blindness	Cereb Cortex
2020	Ribeiro Gomes AR, Olivier E, Killackey HP, Giroud P, Berland M, Knoblauch K, Dehay C, Kennedy H, *co-senior authors, F1000 recommandation	Refinement of the Primate Corticospinal Pathway During Prenatal Development.	Cereb Cortex
2020	Luanda Lins, Florence Wianny, Colette Dehay, Jacques Jestin, Watson Loh	Adhesive Sponge Based on Supramolecular Dimers Interactions as Scaffolds for Neural Stem Cells	Biomacromolecules
2019	Arai Y, Cwetsch AW, Coppola E, Cipriani S, Nishihara H, Kanki H, Saillour Y, Freret-Hodara B, Dutriaux A, Okada N, Okano H, Dehay C, Nardelli J, Gressens P, Shimogori T, D'Onofrio G, Pierani A	Evolutionary Gain of Dbx1 Expression Drives Subplate Identity in the Cerebral Cortex.	Cell Rep
2019	Fousse J, Gautier E, Patti D, Dehay C	Developmental changes in interkinetic nuclear migration dynamics with respect to cell-cycle progression in the mouse cerebral cortex ventricular zone.	J Comp Neurol
2018	Borello U, Kennedy H, Dehay C	The logistics of afferent cortical specification in mice and men	Semin Cell Dev Biol
2018	Magrou L, Barone P, Markov NT, Killackey HP, Giroud P, Berland M, Knoblauch K, Dehay C, Kennedy H, *co-senior authors	How Areal Specification Shapes the Local and Interareal Circuits in a Macaque Model of Congenital Blindness	Cereb Cortex
2018	Wianny F, Kennedy H, Dehay C	Bridging the Gap between Mechanics and Genetics in Cortical Folding: ECM as a Major Driving Force	Neuron
2018	Borello U, Berarducci B, Delahaye E, Price DJ, Dehay C	SP8 Transcriptional Regulation of Cyclin D1 During Mouse Early Corticogenesis.	Front Neurosci
2017	Delaunay D, Kawaguchi A, Dehay C, Matsuzaki F	Division modes and physical asymmetry in cerebral cortex progenitors	Curr Opin Neurobiol