Regional differences in neural crest morphogenesis

Abstract

Neural crest cells are pluripotent cells that emerge from the neural epithelium, migrate extensively, and differentiate into numerous derivatives, including neurons, glial cells, pigment cells and connective tissue. Major questions concerning their morphogenesis include: 1) what establishes the pathways of migration and 2) what controls the final destination and differentiation of various neural crest subpopulations. These questions will be addressed in this review. Neural crest cells from the trunk level have been explored most extensively. Studies show that melanoblasts are specified shortly after they depart from the neural tube, and this specification directs their migration into the dorsolateral pathway. We also consider other reports that present strong evidence for ventrally migrating neural crest cells being similarly fate restricted. Cranial neural crest cells have been less analyzed in this regard but the preponderance of evidence indicates that either the cranial neural crest cells are not fate-restricted, or are extremely plastic in their developmental capability and that specification does not control pathfinding. Thus, the guidance mechanisms that control cranial neural crest migration and their behavior vary significantly from the trunk. The vagal neural crest arises at the axial level between the cranial and trunk neural crest and represents a transitional cell population between the head and trunk neural crest. We summarize new data to support this claim. In particular, we show that: 1) the vagal-level neural crest cells exhibit modest developmental bias; 2) there are differences in the migratory behavior between the anterior and the posterior vagal neural crest cells reminiscent of the cranial and the trunk neural crest, respectively; 3) the vagal neural crest cells take the dorsolateral pathway to the pharyngeal arches and the heart, but the ventral pathway to the peripheral nervous system and the gut. However, these pathways are not rigidly specified because of prior fate restriction. Understanding the molecular, cellular and behavioral differences between these three populations of neural crest cells will be of enormous assistance when trying to understand the evolution of the neck.

Figure 1

Migration pathways of trunk neural crest cells. At the trunk level, neural crest cells first migrate in the intersomitic spaces, followed within a few somite levels (somite VII) by migration through the anterior half of the somite along the basal lamina of the dermamyotome (green lines in box 1). 24 h later neural crest cells switch migration to the dorsolateral path (box 2 and red arrow; red speckling in whole mount). The thick bars indicate the level at which the cross-sections are taken. CV, cardinal vein; DA, dorsal aorta; DM, dermamyotome.

Figure 2

Cranial neural crest cells migrate in the dorsolateral pathway. Beginning at stage 10, cranial neural crest cells migrate dorsolaterally, between the ectoderm and the underlying paraxial mesoderm (grey shading). Representative cross-sections at stages 10 (St 10), 12 (St 12) and 13 (St 13). Once the neural crest cells reach the first branchial arch (labeled BA1 in the St 14 section), they migrate on both sides of the muscles (orange shading) within the forming jaw. The thick bar indicates the level of the representative cross sections. BA1, branchial arch 1; BA2, branchial arch 2; BA3, branchial arch 3; BA4, branchial arch 4; DA, dorsal aorta; CV, cardinal vein; S1, somite 1; S2, somite 2; S3, somite 3; Ph, pharynx; r1–7, rhombomeres 1–7.

Figure 3

The migration of the cranial neural crest cells into the branchial arches. The major streams of neural crest cells originate from the level of rhombomeres 2, 4 and 6 (r2, 4, 6; black arrows) to populate the branchial arches 1, 2 and 3 (BA1, 2, 3), respectively. Some cells from the level of r3 and r 5 (blue arrows) contribute minimally to BA 1, 2 and 3. S1–3, somites 1–3.

Figure 4

Early migratory pathways taken by vagal neural crest cells. Neural crest cells from the level of somites 1–4 initiate their migration in the dorsolateral pathway (between the ectoderm and the dermamyotome) at stage 10 and persist until stage 13 (box A; stage-10 schematic), whereas neural crest cells from the level of somites 5–7 are in the early stages of their ventral migration at stage 10 (box B in stage-10 schematic). By stage 13, neural crest cells from the level of somites 1–4 cease their dorsolateral migration and begin to migrate in the ventral pathway (box A; stage-13 schematic) up until stage 21 (see Reedy et al. 1998). At similar stages, neural crest cells from the level of somites 5–7 continue to migrate in the ventral pathway (box B; stage-13 schematic). DM, dermamyotome; DA, dorsal aorta; Ph, pharynx; S1–S7, somites 1–7.

Figure 5

Distribution of vagal neural crest cells. The dorsolaterally-migrating vagal neural crest cells that originate from the level of somites 1–3 populate the branchial arches 4–6, the outflow tract of the heart and the foregut, as far posteriorly as the esophagus/lung buds region, by stage 22–23. These cells reach the foregut by migrating along the circumpharyngeal ridge (red arrows in inset in A) and populate the lateral region of the foregut (red patch in A at the level of the foregut). The vagal neural crest cells from the level of somite 4 populate the posterior region of branchial arch 6 and more caudal region of the foregut, as far posteriorly as the stomach (at the level of the forelimb), also by migrating along the circumpharyngeal ridge. (B) Starting at stage 13, the ventrally-migrating vagal neural crest cells from the level of somites 1–3 coalesce into the sensory and sympathetic ganglia, and also reach the anterior foregut, by stage 23. In contrast to the dorsolaterally-migrating cells, they populate the dorsal and lateral regions of the foregut (black patch in B at the level of the foregut). The ventrally-migrating neural crest cells from the level of somites 4–6 populate the foregut, as far posteriorly as the stomach (at the level of the forelimb). The neural crest cells from the level of somite 7 only contribute to the dorsal root and sympathetic ganglia. Note that neural crest cells in the ventral pathway do not cross over to the dorsolateral pathway at the circumpharyngeal ridge. Similarly most neural crest cells in the dorsal pathway continue to the branchial arches and the heart, with only a few cells moving medially to occupy the lateral walls of the pharynx. CV, cardinal vein; DA, dorsal aorta; DM, dermamyotome; CPr, circumpharyngeal ridge; SsG, sensory ganglia; SsG/DRG, sensory/dorsal root ganglia; SG, sympathetic ganglia.