Dynamic interactions between intermediate neurogenic progenitors and radial glia in embryonic mouse neocortex: potential role in Dll1-Notch signaling.

ABSTRACT

The mammalian neocortical progenitor cell niche is composed of a diverse repertoire of neuroepithelial cells, radial glia (RG), and intermediate neurogenic progenitors (INPs). Previously, live-cell imaging experiments have proved crucial in identifying these distinct progenitor populations, especially INPs, which amplify neural output by undergoing additional rounds of proliferation before differentiating into new neurons. INPs also provide feedback to the RG pool by serving as a source of Delta-like 1 (Dll1), a key ligand for activating Notch signaling in neighboring cells, a well-known mechanism for maintaining RG identity. While much is known about Dll1-Notch signaling at the molecular level, little is known about how this cell-cell contact dependent feedback is transmitted at the cellular level. To investigate how RG and INPs might interact to convey Notch signals, we used high-resolution live-cell multiphoton microscopy (MPM) to directly observe cellular interactions and dynamics, in conjunction with Notch-pathway specific reporters in the neocortical neural stem cell niche in organotypic brain slices from embryonic mice. We found that INPs and RG interact via dynamic and transient elongate processes, some apparently long-range (extending from the subventricular zone to the ventricular zone), and some short-range (filopodia-like). Gene expression profiling of RG and INPs revealed further progenitor cell diversification, including different subpopulations of Hes1+ and/or Hes5+ RG, and Dll1+ and/or Dll3+ INPs. Thus, the embryonic progenitor niche includes a network of dynamic cell-cell interactions, using different combinations of Notch signaling molecules to maintain and likely diversify progenitor pools.