Neural crest cell plasticity and its limits

Abstract

The quail-chick chimera system (see Box 1) has been used over the years to establish a fate map of the NC along the neural axis. These studies have shown that melanocytes arise from the entire length of the NC in higher vertebrates, whereas mesectodermal derivatives originate only from the cephalic NC region. NC-derived cells that contribute to the PNS and ENS arise only from some areas of the neural axis (Fig. 1).Using the quail-chick system, well-defined areas of the NC have been exchanged to assess NCC plasticity (see Fig. 1). For example, in one study, the vagal region of the NC (which is located between somites 1 and 7, and gives rise to the enteric ganglia) was exchanged with NC from between somites 18 and 24 (which gives rise to the adrenal medulla and sympathetic ganglia) (Le Douarin and Teillet, 1974). This swap resulted Review 4638 in the normal colonisation of the suprarenal gland and sympathetic ganglia by NCCs fated to colonise the gut. However, although the adrenomedullary trunk NCCs invaded the pre-umbilical gut wall and differentiated into normal enteric plexuses, they failed to reach the post-umbilical bowel .This experimental system has since been used together with various molecular markers, such as the Schwann cell myelin protein (SMP), which is present on Schwann cells but not on other PNS and ENS glial cells, to allow a more refined analysis of NCC plasticity. These studies have shown that NCC differentiation into a specific type of glia depends upon the environment in which they develop (Dulac et al., 1988;Dulac and Le Douarin, 1991; Cameron-Curry et al., 1993). Similarly, the differentiation of the various types of autonomic neurons varies according to the milieu in which they differentiate (for reviews, see Le Douarin, 1982;Le Douarin and Kalcheim, 1999).The conclusion of these heterotopic grafting experiments was that the fate of the NCCs that form the PNS and ENS is not fully determined before these cells migrate, but instead remains plastic until they receive differentiation signals at the end of, and possibly during, their migration. This finding raised the issue of whether all the precursors of PNS ganglion cells became fully differentiated and/or committed soon after reaching their sites of arrest, or whether some remained as quiescent undifferentiated cells. This was explored in the experiments discussed in the following section. Undifferentiated precursors in PNS gangliaTo investigate the developmental potentials of PNS ganglion cells, fragments of sensory and autonomic ganglia from quail embryos, taken from embryonic day (E) 4 up to the end of the incubation period, were implanted into NCC migration pathways of E2 chick hosts when their own NCCs were migrating. The grafted neurons themselves died (probably because the necessary survival factors are not present in the younger host). However, the non-neuronal cells of implanted ganglia migrated and homed to host sensory and autonomic ganglia, where they differentiated into the types of neurons and glia corresponding to their novel...

Embryonic origin and Hox status determine progenitor cell fate during adult bone regeneration

“…During development, Hox genes are expressed in a nested pattern along the body axis (Chisaka and Capecchi, 1991;Creuzet et al, 2002;Wellik and Capecchi, 2003;Le Douarin et al, 2004), where they provide cells with positional information. For example, Hoxa11 and Hoxa13 are expressed in limb mesoderm (Wellik and Capecchi, 2003;Knosp et al, 2004;Rinn et al, 2008), where they regulate patterning and morphogenesis of the fetal appendicular skeleton (Tabin, 1995).…”

“…Embryonic cell transplantation experiments have shown that Hox gene expression is a critical determinant of whether grafted cells integrate into their new location (reviewed by Le Douarin et al, 2004). Did a discrepancy in Hox expression underlie the chondrogenic outcome of the adult heterotopic grafts?…”

“…These and additional experiments indicate that the Hox status of a cell confers upon it a sense of positional identity, and this identity is unchanged when cells are placed into a new environment (Le Douarin et al, 2004). There is a 'flip side' to this: mandibular neural crest cells normally lack Hox gene expression and this 'Hox-free' condition has been strongly associated with their remarkable plasticity in development and evolution (reviewed by Helms et al, 2005).…”

Transforming Growth Factor β-Mediated Sox10 Suppression Controls Mesenchymal Progenitor Generation in Neural Crest Stem Cells

“…The potential to generate chondrocytes and osteocytes has mainly been attributed to cranial neural crest (NC) cells [1]. In support of this, multipotent progenitors with neural as well as mesenchymal potentials were rarely observed in clonal cell culture assays of trunk NC cells [2,3] and trunk NC was ineffective in forming cartilage after transplantation in vivo [4].…”

The proliferating field of neural crest stem cells

“…Direct tests of the potency, self-renewal, and molecular characteristics of SKPs and MSCs during late phases of the hair cycle when the stem cell-containing bulge region and the melanocytecontaining hair papilla are physically most discrete should address this issue. Currently, understanding of the in vivo lineage relationships between different types of NCCs is limited, but a detailed model based on extensive characterization of pluripotentiality of cultured NCCs has been proposed by the Le Douarin lab Le Douarin et al, 2004;Dupin et al, 2007). As noted above, several of the intermediates they proposed show at least some capacity for self-renewal (Trentin et al, 2004); as in vivo lineage relationships and progenitor types become clearer, it will be important to establish their self-renewal capacity.…”