Neuromesodermal progenitor origin of trunk neural crestin vivo

Abstract

Neural crest (NC) is a vertebrate-specific population of multipotent embryonic cells predisposed to particular derivatives along the anteroposterior (A-P) axis. While only cranial NC progenitors give rise to ectomesenchymal cell types, trunk NC is biased for neuronal cell fates. By integrating multimodal single-cell analysis we uncovered heterogenous NC cells across the entire A-P axis expressing NC regulator foxd3. We pinpointed to its specific cranial and trunk auto-regulated enhancers. The trunk foxd3 enhancer, however, did not mark the bona fide NC, but bipotent tailbud neuromesodermal progenitors (NMps). A subset of these NMp-derived pro-neural cells appeared to give rise to neuronal trunk NC in amniotes in vivo, suggesting that at least a portion of trunk NC progenitors with a bias for neuronal fates originated from NMps in vivo.

Rostrocaudal patterning and neural crest differentiation of human pre-neural spinal cord progenitors in vitro

“…Together this work suggests that the CNS and derivatives of trunk/sacral NC (such as the peripheral nervous system) arise from a common PNP derived from the NMP population. This finding has recently been supported by studies in vivo (Lukoseviciute et al, 2021). Surprisingly, the addition of the BMP inhibitor LDN did not prevent NC specification in long-term PNPs, although only intermediate levels of BMP signaling are required to robustly induce NC commitment (Frith et al, 2018;Hackland et al, 2017).…”

From Bipotent Neuromesodermal Progenitors to Neural-Mesodermal Interactions during Embryonic Development

“…More recently, using a trunk-specific foxd3 enhancer to trace the lineage of NC cells in vivo, tailbud NMPs were also labeled. Subsequently, labeling was encountered in cells that express neural plate border and early NC genes and in neuronal trunk derivatives such as dorsal root ganglia [8]. Together, these results suggest that at least some trunk-level NC progenitors also derive from NMPs.…”

“…An intriguing question is what NC populations emanate from NMPs [8], are these primarily neural progenitors or also melanocytes? Additional labeling strategies should be implemented to address the lineage of the trunk NC back to these fascinating postgastrulation progenitors, followed by exploring mechanisms of lineage segregation.…”

Shaping axial identity during human pluripotent stem cell differentiation to neural crest cells

“…Similarly, lineage tracing of cells expressing NMP markers such as Nkx1–2 , Tbx6/Sox2 , Bra/T and FoxB1 revealed that these contribute to neural, mesodermal and NC lineages [ 58 , 61 , 63–68 ]. More recent work, using single-cell transcriptomics and epigenomic profiling in zebrafish, has further demonstrated that posterior NC is derived from an NMP-derived pre-neural intermediate [ 69 ]. Taken together these data strongly suggest that, at least a fraction of trunk and sacral NC are directly derived from axial progenitors, which are competent to generate presomitic mesoderm.…”