The molecular basis underlying the transition between neural crest to roof plate

Upon closure of the neural folds, the resulting dorsal midline region of the neural tube (NT) is generally termed the roof plate (RP). This domain is highly dynamic and complex being first transiently inhabited by prospective neural crest (NC) cells that sequentially emigrate from the neuroepithelium. Whereas much is known about NC ontogeny, the molecular mechanisms underlying the end of NC production and formation of the RP remain unknown.
In previous studies, our lab has shown that in the developing NT a gradient of BMP4 control NC emigration through canonical Wnt signaling. The transition between NC and RP is associated with the end of responsiveness to BMP and the advent of Hairy1/Hes4 signaling.
To further understand the molecular basis of NC to RP transition, it is imperative to define the molecular differences between NC and RP cells and their functional implications to the process. To this end, we performed a transcriptome analysis of cells at NC and RP stages. This revealed the presence of about 1000 genes that were either down- or upregulated in RP when compared to NC. Several genes were further validated by in situ hybridization and functional analysis is already underway.
Among the salient family of differentially expressed genes, we found a decrease in genes leading to epithelial-mesenchymal transition. Furthermore, cell cycle genes were downregulated in agreement with the RP becoming a post-mitotic structure. Conversely, molecules associated with CNS development were upregulated. Thus, we have generated a battery of differential genes whose functional analysis is underway.