Hindbrain Boundaries- a new niche of neural progenitors/stem cells regulated by Sox2-FGF-ECM crosstalk

An important developmental mechanism lays in the formation of compartment boundaries, arising between different-fated cell populations, destined to orchestrate proper morphogenesis and tissue patterning. The hindbrain is an excellent model to investigate the significance of boundaries. In all vertebrates, the embryonic hindbrain is composed of repetitive segments,

termed rhombomeres, which are separated by well-defined boundaries. While each rhombomere is a cell-lineage-restricted compartment with its individual genetic and cellular fates, cells in the hindbrain boundaries (HBs) are similar. They share a specialized morphology, signaling factors, ECM components and an ability to regenerate once removed, altogether stresses their likely significance. Although HBs were identified a while ago, their role during development remained vague, especially in amniotes.

We have recently found that HBs of chick and mouse embryos express the neural progenitor/stem cells (NPSCs) gene Sox2, while also being surrounded by the ECM molecule chondroitin sulphate proteoglycan (CSPG). Moreover, we found that through regulation of Sox2 expression, HBs act as reservoirs of NPSCs, providing new progenitors to the rhombomeres. However, the mechanisms governing the formation and maintenance of HB cells as NPSC, as well as the involvement of signaling molecules and the ECM, are not clear.

By conducting RNAseq on rhombomeres versus HB cells, together with applying loss- and gain-of function approaches in mouse and chick embryos in vivo and in vitro, we were able to mark novel HB-inclined genes. We show for the first time that HBs represent a unique microenvironment in amniotes that promote the development of NPSCs via FGF-CSPG dependent action.