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

Abstract

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.

In vivo Neural Crest Cell Migration Is Controlled by “Mixotaxis”

“…This is reinforced by the fact that placodes are also the source of negative regulators of NC motility such as semaphorins rendering their vicinity non-permissive for migration (Yu and Moens, 2005;Bajanca et al, 2019). Interestingly, physical and chemical confinement together with intrinsic motility, CIL and mutual attraction are sufficient to drive directed NC migration even in absence of a stiffness gradient or a chemotactic cue (Szabo et al, 2016;Szabó et al, 2019).…”

Rules of collective migration: from the wildebeest to the neural crest

“…At all scales, although the three rules of attraction, repulsion and alignment can generate collective motility, they are insufficient to explain persistent directional collective migration; instead, external signals are required to direct movement. For the neural crest, collective chemotaxis to placodal cells secreting SDF1 is essential in determining directionality [64,89,90]. The mechanism by which the cranial neural crest of Xenopus and zebrafish undergo collective chemotaxis has been recently elucidated; this shows that the neural crest move by supracellular migration, which is a type of collective migration whereby movement can be better described by the behaviour and activity of the group as a whole rather than by the individuals of which it is comprised [108].…”

Evolutionary and Developmental Associations of Neural Crest and Placodes in the Vertebrate Head: Insights From Jawless Vertebrates

“…In cases where both cell populations contribute to ganglia (e.g., epibranchial), earlier-migrating placode cells are usually followed closely behind by cranial neural crest, whereas other placodes, such as the otic, may act as barriers that shape the migratory paths of cranial neural crest originating from the hindbrain en route to the pharyngeal arches ( Steventon et al, 2014 ). Although not all cranial neural crest cells contribute to cranial ganglia, there is evidence that they may physically segregate and individuate placode-derived ganglionic clusters during migration, a phenomenon which may be reciprocated by placodes to enable the formation of neural crest streaming in the head ( Theveneau et al, 2013 ; Szabó et al, 2019 ). These types of intercellular interactions can occur quite early in development, with neural crest and placodes each appearing to be required for the other to undergo migration and morphogenesis of craniofacial structures in a “chase-and-run” model whereby early migrating placodes chemoattract ( via Sdf ) trailing neural crest cells that express the corresponding receptor ( CXCR4 ; Theveneau et al, 2010 , 2013 ).…”