Completion of Neural Crest cell Production and Emigration is Regulated by Retinoic Acid-dependent Inhibition of BMP Signaling

The dorsal midline of the embryonic neural tube (dNT) is a highly dynamic region, populated first by the Neural Crest (NC), a migratory subset of cells that generate most of the peripheral nervous system, pigment cells and ectomesenchyme. After the completion of NC emigration, the dorsal midline is occupied by the definitive Roof Plate (RP), whose function is crucial for development and patterning of dorsal spinal interneurons. The mechanisms underlying the end of NC production and consecutive formation of the definitive RP, remained largely unknown.

We recently reported that dNT-derived retinoic acid is responsible for the completion of NC production and emigration, acting through suppresion of BMP signaling. Interestingly, inhibition of retinoic acid signaling prolonged the lifetime of the NC while partially affecting formation of the definitive RP. Whereas several RP-specific genes are normally expressed in absence of retinoic acid activity, RP and NC genes are co-expressed in single cells and this domain is also infiltrated by dorsal interneurons and their processes. Hence, the cellular and molecular architecture underlying fate segregation of the above lineages is dependent on a network comprising retinoic acid and BMP signaling. We aim to expand our knowledge of the mechanisms segregating between NC and RP lineages, by analysing the transcriptional profiles of both normal and retinoic acid-deficient dNT cells, with single-cell resolution. Using this approach, we also expect to achieve a novel understanding of RP properties, its interactions with dorsal interneurons, and possible mechanisms conducive to abnormal development.