Investigation of Factors that Determine Cell Fate and Tube Polarity in the Developing Neural Tube

Authors

• J Rees
• J Kirkland
• C Pajanoja
• A Schiffmacher
• L Kerosuo

Abstract

The neural crest is a unique migratory stem cell population that forms in the dorsal neural tube during neurulation and is thought to be distinct from the rest of the neural tube that forms the central nervous system. However, the dorsal and ventral neural tube have several similarities during neurulation – both act as hinge points, essential for neural tube closure, and both act as opposing signaling centers. Furthermore, we find that the neural crest marker gene FOXD3, is expressed in both the dorsal and ventral poles of the neural tube bringing into question whether it has shared roles at these poles unrelated to neural crest specification. This project aims to identify genes coexpressed in both the dorsal and ventral neural tube and characterize their function. Using single-cell RNA seq analysis in chick, coupled with validation by HCR in situ hybridization, we have found genes linked to neural crest delamination (FOXD3, SOX5, OLFML3), and cell adhesion (COTL1 and FBLN1), co-expressed in the dorsal and ventral poles of the neural tube indicating a role for these genes in neural tube hinging. Furthermore, FOXD3 loss-of-function experiments in chick have identified potential novel roles for patterning and polarisation of the ventral neural tube, in addition to its known role in neural crest specification. This work helps identify unexplored functions of FOXD3, and better understand the role of epithelial–mesenchymal transition during neurulation. This work was funded by the Intramural Research Program at the NIDCR (NIH DE000748-04).

Scientific Focus Area: Developmental Biology

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