Instructive Role of Wnt/ß-Catenin in Sensory Fate Specification in Neural Crest Stem Cells

Abstract

Wnt signaling has recently emerged as a key factor in controlling stem cell expansion. In contrast, we show here that Wnt/beta-catenin signal activation in emigrating neural crest stem cells (NCSCs) has little effect on the population size and instead regulates fate decisions. Sustained beta-catenin activity in neural crest cells promotes the formation of sensory neural cells in vivo at the expense of virtually all other neural crest derivatives. Moreover, Wnt1 is able to instruct early NCSCs (eNCSCs) to adopt a sensory neuronal fate in a beta-catenin-dependent manner. Thus, the role of Wnt/beta-catenin in stem cells is cell-type dependent.

Controlled levels of canonical Wnt signaling are required for neural crest migration

“…However, here sensory neurogenesis was also impaired. Another study in mouse, contradicting zebrafish data shows that sustained ß-catenin activity in NC cells promoted the generation of sensory neurons, but had no effect on melanocyte formation (Lee et al, 2004). A later study using different Cre-lines to activate ß-catenin signaling at specific time points during NC development proved a temporal separation in generation of NC derivatives where sensory neurons are determined earlier than melanocytes (Hari et al, 2012).…”

“…Canonical Wnt signaling has been associated with development of craniofacial structures and NC derivatives including melanocytes and sensory neural cells (Dorsky et al, 1998;Brault et al, 2001;Hari et al, 2002;Lee et al, 2004;Lewis et al, 2004;Hari et al, 2012). In zebrafish, overexpression of ß-catenin in premigratory NC cells has been shown to promote pigment cell formation at the expense of neurons and glia, while inhibition of Wnt signaling using a truncated form of Tcf3 or a dominant-negative Wnt1 caused an opposite effect promoting neuronal fate at the expense of pigment cells (Dorsky et al, 1998).…”

“…Thus, even after migration there seem to be a clear-cut time windows where canonical Wnt signaling exerts certain functions in the development of NC cells. Interestingly, in none of these studies comprising in vitro and in vivo analysis in the mouse model system, any defects in NC migration have been observed (Brault et al, 2001;Hari et al, 2002;Lee et al, 2004). However, it is worth noting that sustained ß-catenin signaling in the mouse has been shown to prevent cranial NC cells from entering the branchial arches (Lee et al, 2004) indicating that NC migration should also be affected.…”

“…Interestingly, in none of these studies comprising in vitro and in vivo analysis in the mouse model system, any defects in NC migration have been observed (Brault et al, 2001;Hari et al, 2002;Lee et al, 2004). However, it is worth noting that sustained ß-catenin signaling in the mouse has been shown to prevent cranial NC cells from entering the branchial arches (Lee et al, 2004) indicating that NC migration should also be affected. In addition, the growing concern on the usage of mouse as a model system for the study of NC development supports the necessity to use complementary systems (Barriga et al, 2015).…”

“…Wnt signaling was shown to be required for BMP activation during second step of NC induction in chick embryo (Patthey et al, 2009 (Lee et al, 2004). In zebrafish,…”