Coming full circle: Neural crest marker FOXD3 regulates SHH expression in the floorplate and neural tube...

The unique nature of neural crest cells has encouraged the characterization of the dorsal neural tube as distinct from the rest of the neural tube. Yet the dorsal and ventral neural tube have several similarities during neurulation, both acting as hinge points and opposing signaling centers. Furthermore, we find that the neural crest marker gene FOXD3, is expressed in both the dorsal and ventral neural tube, indicating shared roles unrelated to neural crest specification. This project aimed to identify genes coexpressed in the dorsal and ventral neural tube and characterize ventral FOXD3 function.

Using single cell RNA sequencing analysis in chick, coupled with HCR in situ hybridization, we found genes linked to neural crest delamination (FOXD3, SOX5, OLFML3), cell adhesion (COTL1, FBLN1), and GTP-binding (DLC1, ARL4A) co-expressed in the dorsal and ventral neural tube. Using loss-of-function experiments in chick we identify a novel role for FOXD3 in patterning the ventral neural tube through regulating SHH expression in the floorplate and show that FOXD3 is essential for neural tube hinging and morphogenesis.

This work identifies unexplored functions of FOXD3, and identifies dual functions for neural crest EMT and specification genes in controlling tube morphogenesis. NIH ZIA DE000748-04, ZIC DE000750-01.