Neural crest streaming as an emergent property of tissue interactions during morphogenesis

A fundamental question in embryo morphogenesis is how a complex pattern is established in seemingly uniform tissues. During vertebrate development, neural crest cells differentiate as a continuous mass of tissue along the neural tube and subsequently split into spatially distinct migratory streams to invade the rest of the embryo. How these streams are established is not well understood. Inhibitory signals surrounding the migratory streams led to the idea that position and size of streams are determined by a pre-pattern of such signals. While clear evidence for a pre-pattern in the cranial region is still lacking, all computational models of neural crest migration published so far have assumed a pre-pattern of negative signals that channel the neural crest into streams. Here we test the hypothesis that instead of following a pre-existing pattern, the cranial neural crest creates their own migratory pathway by interacting with the surrounding tissue. By combining theoretical modeling with experimentation, we show that streams emerge from the interaction of the hindbrain neural crest and the neighboring epibranchial placodal tissues, without the need for a pre-existing guidance cue. Our model suggests that the initial collective neural crest invasion is based on short-range repulsion and asymmetric attraction between neighboring tissues. The model provides a coherent explanation for the formation of cranial neural crest streams in concert with previously reported findings and our new in vivo observations. Our results point to a general mechanism of inducing collective invasion patterns.Author summary: A central question in morphogenesis is how complexity arises from unpatterned tissues. One crucial event in vertebrate development is the migration of neural crest cells into stereotypic streams. Cranial neural crest cells start their migration as a single tissue mass but invade their environment and migrate in distinct streams. While this stream migration is crucial for correct head development and is relatively well studied, it is unclear how the initial stream patterns are formed. Surrounding tissues lack a clear organization prior to neural crest migration, making the existence of a guiding pre-pattern unlikely. In this study we address the question of how the initial neural crest streams are formed by combining theoretical modeling with experimentation and show that neural crest streams emerge from dynamic interactions with neighboring tissues.