Biology subjects

Baffet, A. D.

Publications and source records attributed to Baffet, A. D..

4 recordsLinked to original sources

bioRxiv2026

A defined 2D system for generating and expanding human basal radial glia from iPSCs

Basal radial glia (bRG) drive human cortical expansion but remain underrepresented in vitro. We established a defined and expandable 2D system for efficient generation of human bRG from iPSCs. These cells recapitulate canonical molecular signatures, hallmark somal translocation behaviours, intrinsic differentiation potential, and integration into organoid tissue. Network-based analyses identified PAK2 as a regulator of mitotic somal translocation, illustrating the systems utility for mechanistic interrogation of bRG biology.

neuroscience↗

bioRxiv2025

Two independent translocation modes drive neural stem cell dissemination into the human fetal cortex

The strong size increase of the human neocortex is supported both by the amplification and the basal translocation of a neural stem cell population, the basal radial glial cells (or bRG cells). Using live imaging of second trimester human fetal tissue and cortical organoids, we identify two independent translocation modes for bRG cell colonization of the human neocortex. On top of an actomyosin-dependent movement called mitotic somal translocation (MST), we identify a microtubule-dependent motion occurring during interphase, that we call interphasic somal translocation (IST). We show that IST is driven by the LINC complex, through the nuclear envelope recruitment of the dynein motor and of its activator LIS1. Consequently, IST severely altered in LIS1 patient-derived cortical organoids. We also demonstrate that MST occurs during prometaphase and is a mitotic spindle translocation event. MST is controlled by the mitotic cell rounding molecular pathway, via Moesin and Vimentin, driving translocation. We report that 85% of bRG cell translocation is due to IST, for a total movement of 0,67 mm per month of human fetal gestation. Our work identifies how bRG cells colonize the human fetal cortex, and further shows that IST and MST are conserved in bRG-related migrating glioblastoma cells.

neuroscience↗

bioRxiv2021

Regulation of neuronal progenitor delamination by dynein-driven post-Golgi apical transport

Radial glial (RG) cells are the neural stem cells of the developing neocortex. Apical RG (aRG) cells can delaminate to generate basal RG (bRG) cells, a cell type associated with human brain expansion. Here, we report that this delamination is regulated by the post-Golgi secretory pathway. Using in situ subcellular live imaging, we show that post-Golgi transport of RAB6+ vesicles occurs toward the minus ends of microtubules and depends on dynein. We demonstrate that the apical determinant Crumbs3 (CRB3) is also transported by dynein. Double knockout of RAB6A/A and RAB6B impairs apical localization of CRB3, and induces a retraction of aRG cell apical process, leading to delamination and ectopic division. These defects are phenocopied by knock-out of the dynein activator LIS1. Overall, our results identify a RAB6-dynein-LIS1 complex for Golgi to apical surface transport in aRG cells, and highlights the role of this pathway in the maintenance of neuroepithelial integrity.

cell biology↗

bioRxiv2020

A dendritic-like microtubule network is organized from swellings of the basal fiber in neural progenitors

Neurons of the neocortex are generated by neural progenitors called radial glial cells. These polarized cells extend a short apical process towards the ventricular surface and a long basal fiber that acts as a scaffold for neuronal migration. How the microtubule cytoskeleton is organized in these cells to support long-range transport in unknown. Using subcellular live imaging within brain tissue, we show that microtubules in the apical process uniformly emanate for the pericentrosomal region, while microtubules in the basal fiber display a mixed polarity, reminiscent of the mammalian dendrite. We identify acentrosomal microtubule organizing centers localized in swellings of the basal fiber. We characterize their distribution and demonstrate that they accumulate the minus end stabilizing factor CAMSAP3 and TGN-related membranes, from which the majority of microtubules grow. Finally, using live imaging of human fetal cortex, we show that this organization is conserved in basal radial glial (bRG) cells, a highly abundant progenitor cell population associated with human brain size expansion.

cell biology↗