Biology subjects

Lampic, M.

Publications and source records attributed to Lampic, M..

3 recordsLinked to original sources

bioRxiv2022

A cell fate decision map reveals abundant direct neurogenesis in the human developing neocortex

The human neocortex has undergone strong evolutionary expansion, largely due to an increased progenitor population, the basal radial glial (bRG) cells. These cells are responsible for the production of a diversity of cell types, but the successive cell fate decisions taken by individual progenitors remains unknown. Here, we developed a semi-automated live/fixed correlative imaging method to generate a map of bRG cell division modes in early fetal tissue and cerebral organoids. Through the analysis of over 1,000 dividing progenitors, we show that bRG cells undergo abundant symmetric amplifying divisions, followed by frequent direct neurogenic divisions, bypassing intermediate progenitors. These direct neurogenic divisions are more abundant in the upper part of the subventricular zone. We furthermore demonstrate asymmetric Notch activation in the self-renewing daughter cells, independently of basal fiber inheritance. Our results reveal a remarkable conservation of fate decisions in cerebral organoids, supporting their value as models of early human neurogenesis.

developmental biology↗

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↗

bioRxiv2018

Restoration of visual function by transplantation of optogenetically engineered photoreceptors

A major challenge in the treatment of retinal degenerative diseases, with the transplantation of replacement photoreceptors, is the difficulty in inducing the grafted cells to grow and maintain light sensitive outer segments (OS) in the host retina, which depends on proper interaction with the underlying retinal pigment epithelium (RPE). For a RPE-independent treatment approach, we introduced a hyperpolarizing microbial opsin into photoreceptor precursors from new-born mice, and transplanted them into blind mice lacking the photoreceptor layer. These optogenetically transformed photoreceptors were light responsive and their transplantation lead to the recovery of visual function, as shown by ganglion cell recordings and behavioral tests. Subsequently, we generated cone photoreceptors from human induced pluripotent stem cells (hiPSCs), expressing the chloride pump Jaws. After transplantation into blind mice, we observed light-driven responses at the photoreceptor and ganglion cell level. These results demonstrate that structural and functional retinal repair is possible by combining stem cell therapy and optogenetics.

bioengineering↗