Regulation of neural crest cell populations: occurrence, distribution and underlying mechanisms.

Regulation is a significant developmental event because successful cell proliferation and migration are critical to shaping young embryos. Regulation -- the replacement of undifferentiated embryonic cells by other cells in response to signals received from the environment -- is distinct from wound healing and regeneration. Investigations on regulation of neural crest cells span all vertebrates and have revealed that regulative ability varies both among classes (even species), and spatially and temporally within individuals. In general, there is greatest regulation for cranial neural crest cells, less for trunk, and virtually none forcardiac. Regulation also appears to be more complete at early embryonic stages. Fate-mapping studies have demonstrated that large regions of neural crest cells must be removed to generate missing or morphologically reduced structures. Recent studies reveal that less extensive neural crest cell extirpations result in normal morphology of cartilaginous and neuronal elements in the head, and normal development of pigmentation in the trunk. Ablation of cardiac neural crest cells frequently generates abnormalities of the heart, great vessels and parasympathetic nerve innervation. Decreased cell death, increased division, change in fate and altered migration are possible cellular mechanisms of regulation. In mostcases, the specific mechanisms of regulation are unknown, but a major premise underlying regulation is that cell potential is greater than cell fate. This concept was born from studies which demonstrated that some cells were able to express alternative fates if transplanted to a new environment. Among the potential cellular mechanisms for regulation, cell migration has received the most attention. Following ablation of neural crest cells, replacement neural crest cells migrate into gaps, most frequently from anterior/posterior locations. Cells from surrounding epidermal and neural ectoderm may have limited regulative ability, while compensation by cells from the ventral neural tube has been demonstrated to an even lesser extent. Regulation by such non-crest cells would require their transformation into neural crest cells. The potential for regulation of neural crest by placodal cells supports a closer relationship between neural crest and placodal ectoderm than previously recognized. Decreased cell death has been discussed primarily with reference to (1) cranial ganglia that have dual contributions from neural crest and placodal cells and (2) programmed cell death in rhombomeres three and five. Increased cell division in response to neural crest ablation is likely more common than has been reported, but this mechanism is difficult to interpret without a 3-D context for viewing how patterns of division differ from normal. Lastly, changes in cell fate may be the driving factor in regulation of embryonic cells. It has been repeatedly demonstrated thatcell potential is greaterthan cell fate. Once reliable mechanisms for assessing cell potential are established, we may find that fates are commonly altered in response to environmental signals. Regulation is therefore significant both as a basic developmental mechanism and as a mechanism for evolutionary change. The more labile the fate of embryonic cells, the more potential there is for maintaining existing characters and for generating new ones. According to Ettensohn (1992, p. 50), further analysis of such systems might <<shed light both on the way evolutionary processes act to modify ontogenetic programs and on the cellular and molecular mechanisms of cell interactions during development>>. With regard to the neural crest, studies on regulation of this vital population of cells provide insight to the origin of the neural crest, to embryonic repair, and to the source of many craniofacial malformations, heart and other embryonic defects. (ABSTRACT TRUNCATED)