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).
|2016||524(3):535-63||Unsupervised lineage-based characterization of primate precursors reveals high proliferative and morphological diversity in the OSVZ||Pfeiffer M, Betizeau M, Waltispurger J, Pfister SS, Douglas RJ, Kennedy H, Dehay C||J Comp Neurol||-|
|2015||09:33||Mitotic spindle asymmetry in rodents and primates: 2D vs. 3D measurement methodologies||Delaunay D, Robini MC, Dehay C||Front Cell Neurosci||-|
|2015||85(4):683-94||The outer subventricular zone and primate-specific cortical complexification||Dehay C, Kennedy H, Kosik KS||Neuron||-|
|2014||6(2):400-14||Mitotic spindle asymmetry: a Wnt/PCP-regulated mechanism generating asymmetrical division in cortical precursors||Delaunay D, Cortay V, Patti D, Knoblauch K, Dehay C||Cell Rep||-|
|2014||81(6):1255-62||Novel primate miRNAs coevolved with ancient target genes in germinal zone-specific expression patterns||Arcila ML, Betizeau M, Cambronne XA, Guzman E, Doerflinger N, Bouhallier F, Zhou H, Wu B, Rani N, Bassett DS, Borello U, Huissoud C, Goodman RH, Dehay C, Kosik KS||Neuron||-|