The nervous system starts as a tube of cells which will form the brain and the spinal cord. The dorsal neural tube first generates Neural Crest cells that exit their site of origin to migrate throughout the embryo and form the peripheral nervous system and more. After a while this emigration curiously stops, and new cells arriving in the dorsal domain of the neural tube stay there and form the definitive Roof Plate which is crucial for development of dorsal interneurons. A lot is known about Neural Crest progenitors, what defines them, what makes them leave the neural tube and migrate to specific sites, but almost nothing was known about how the Neural Crest emigration stage is completed, and what causes the formation of the Roof Plate. In this study we uncover that dorsal neural tube-derived Retinoic Acid controls the end of Neural Crest production and the subsequent transition into the Roof Plate, by regulating BMP signaling activity. We show that in the absence of Retinoic Acid activity, Neural Crest- specific genes and cellular traits persist well into the Roof Plate stage, including extended cell emigration. In addition, while selected Roof Plate characteristics depend on Retinoic Acid, other features do not, suggesting that the end of Neural Crest production and formation of the Roof Plate, are in part independently regulated.
Take home message: Retinoic Acid-dependent BMP signaling is key to the segregation between the central and peripheral lineages of the nervous system during embryogenesis.
A- Graphic summary of the main results. In the absence of Retinoic acid activity, the period of neural crest production and emigration is extended and neural crest and roof plate lineages fail to segregate.
B- A proposed model accounting for the transition between peripheral (neural crest) and central (roof plate) components of the nervous system.
Glossary: Neural crest– progenitors born in the dorsal neural tube that emigrate and generate most of the neurons and glia of the peripheral nervous system. Roof plate– the dorsal domain of the developing spinal cord, acts as a signaling center for interneuron development. BMP– Bone morphogenetic protein, a master regulator of neural crest emigration. Wnt– a morphogen responsible for neural crest proliferation. EMT– epithelial to mesenchymal transition, a process that leads to the onset of cell migration.