Pentimento: Neural Crest and the origin of mesectoderm

The Neural Crest, a transient epithelium in vertebrate embryos, is the source of putative stem cells known to give rise to neuronal, glial and endocrine components of the peripheral (sensory, autonomic and enteric) nervous system (PNS) and pigment cells in the skin. The Neural Crest is also widely believed to be the source of mesectodermal derivatives (skeletogenic, odontogenic, connective tissue and smooth muscle mesenchyme) in the vertebrate head [see (Bronner and LeDouarin, 2012; Le Douarin, 2012; Le Douarin and Kalcheim, 1999); see also (Hörstadius, 1950; Weston, 1970)]. This conventional understanding of the broad developmental potential of the Neural Crest has been challenged over the past few years (Breau et al., 2008; Lee et al., 2013a, 2013b; Weston et al., 2004), based on recognition that the definition of the embryonic epithelia that comprise the Neural Crest may be imprecise. Indeed, the definition of the embryonic tissues understood to constitute the Neural Crest has changed considerably since it was first described by Wilhelm His 150 years ago (His, 1868). Today, the operational definition of the Neural Crest is inconsistent and functionally ambiguous. We believe that more precise definitions of the embryonic tissues involved in Neural Crest development would be useful to understand (1) the range of cellular phenotypes that actually segregate from it, (2) when this lineage diversification occurs, and (3) how diversification is regulated. In this idiosyncratic review, we aim to explain our concerns with the current definitions in this field, and in the chiastic words of Samuel Johnson (1781), "… make new things familiar and familiar things new".(1) Then, we will try to distinguish the developmental events crucial to the regulation of Neural Crest development at both cranial and trunk axial levels of vertebrate embryos, and address some of the implicit assumptions that underlie the conventional interpretation of experimental results on the origin and fates of Neural Crest-derived cells. We hope our discussion will resolve some ambiguities regarding both the range of derivatives in the Neural Crest lineage and the conventional understanding that cranial mesectodermal derivatives share a common Neural Crest-derived lineage precursor with components of the PNS.