Using 9 different glioblastoma lines we show that IST and MST both occur, although not in all cells, reflecting the heterogeneity of these tumors. Strikingly, glioblastoma undergoing IST and MST did so using the same molecular mechanism as the ones identified here in bRG cells.

So MST and IST are totally different mechanisms, but what is their relative contribution to bRG dissemination in the human fetal cortex? After extensive recording in fetal explants, Ryszard could show that IST contributes to 85% of the total basal movement, while MST contributes to 15%.

Mechanistically, we demonstrate that MST is dependent on the mitotic cell rounding pathway, that enables most adherent cells to round up for proper chromosome segregation through an increase of the cell cortex stiffness. Knocking down ERM proteins (Ezrin-Radixin-Moesin) or Vimentin all alter MST.

We demonstrate that IST is dependent on the dynein motor and its activator LIS1. Accordingly, IST is severely affected in LIS1-patient derived organoids (Lissencephalic). We also show that the dynein-LIS1 complex is recruited to the nuclear enveloppe (and underlying Lamins) via the LINC complex.

On top of identifying the mechanism for MST, we realised that bRG cells also translocate during interphase, a process we call Interphasic Somal Translocation (IST). We show that IST is microtubule dependent and actomyosin independent, while MST is actomyosin-dependent and microtubule independant.

Great work from @ryszardwimmer.bsky.social, who live imaged and manually tracked over 11,000 human bRG cells, for 48-96 hours 😱. (I feel bad)
What he realised is that bRG cells have two, totally independent modes of migration, for which he managed to identify the molecular mechanisms.

Our new paper is out in BioRxiv. Using human fetal tissue and cortical organoids, we figured out how human bRG cells colonize the developing neocortex to expand the oSVZ stem cell niche. Turns out, it's a more complex process than we had anticipated!
www.biorxiv.org/content/10.1...