Neuropilin 1 signaling guides neural crest cells to coordinate pathway choice with cell specification

Abstract

Neural crest cells (NCCs) are highly motile embryonic stem cells that delaminate from the neuroectoderm early during vertebrate embryogenesis and differentiate at defined target sites into various essential cell types. To reach their targets, NCCs follow 1 of 3 sequential pathways that correlate with NCC fate. The firstborn NCCs travel ventrally alongside intersomitic blood vessels to form sympathetic neuronal progenitors near the dorsal aorta, while the lastborn NCCs migrate superficially beneath the epidermis to give rise to melanocytes. Yet, most NCCs enter the somites to form the intermediate wave that gives rise to sympathetic and sensory neurons. Here we show that the repulsive guidance cue SEMA3A and its receptor neuropilin 1 (NRP1) are essential to direct the intermediate wave NCC precursors of peripheral neurons from a default pathway alongside intersomitic blood vessels into the anterior sclerotome. Thus, loss of function for either gene caused excessive intersomitic NCC migration, and this led to ectopic neuronal differentiation along both the anteroposterior and dorsoventral axes of the trunk. The choice of migratory pathway did not affect the specification of NCCs, as they retained their commitment to differentiate into sympathetic or sensory neurons, even when they migrated on an ectopic dorsolateral path that is normally taken by melanocyte precursors. We conclude that NRP1 signaling coordinates pathway choice with NCC fate and therefore confines neuronal differentiation to appropriate locations.semaphorin ͉ sensory neuron ͉ sympathetic neuron ͉ peripheral nervous system

Neuropilin-mediated neural crest cell guidance is essential to organise sensory neurons into segmented dorsal root ganglia

“…Neuropilin-mediated neural crest cell guidance is essential to organise sensory neurons into segmented dorsal root ganglia (Schwarz et al, 2009). By contrast, most other NCCs that give rise to neurons and glia in the trunk migrate through the anterior half of the somite, after it has segregated into sclerotome and dermomyotome layers.…”

“…However, loss of the repulsive guidance cue SEMA3F or its receptor NRP2 in the mouse causes NCC invasion into both anterior and posterior sclerotome without disrupting the metameric pattern of the sympathetic or dorsal root ganglia (DRG) (Gammill et al, 2006;Waimey et al, 2008). We have since shown that the related SEMA3A/NRP1 pathway provides an alternative mechanism for trunk NCC guidance (Schwarz et al, 2009). Specifically, loss of SEMA3A or NRP1 leads to excessive NCC migration along intersomitic and perisomitic routes and consequently to ectopic sensory and sympathetic neuron differentiation.…”

A novel role for MuSK and non-canonical Wnt signaling during segmental neural crest cell migration

“…Although the role of Eph signaling during segmental neural crest cell migration remains unclear (Adams et al, 2001;Davy et al, 2004;Wang et al, 1998), recent studies demonstrate multiple functional roles for Neuropilin (Nrp)/Semaphorin (Sema) signaling in this process. Nrp1/Sema3A signaling repels neural crest cells from the intersomitic space to the sclerotome, and Nrp2/Sema3F signaling functions to restrict neural crest cell migration to the anterior half of the sclerotome (Gammill et al, 2006b;Schwarz et al, 2009a;Schwarz et al, 2009b). Finally, combined loss of Nrp1 and Nrp2 signaling results in perturbation of DRG segmentation, whereas metameric organization of sympathetic ganglia remains unaffected (Roffers-Agarwal and Gammill, 2009).…”

Pilot Study on “Pericytic Mimicry” and Potential Embryonic/Stem Cell Properties of Angiotropic Melanoma Cells Interacting with the Abluminal Vascular Surface

“…In addition, cancer stem cells are also able to migrate, however, current studies on migrating cancer stem cells are very limited, mainly due to the lack of specific markers to isolate migrating cancer stem cells [14]. Pertinent to the potential migratory stem cell properties of angiotropic MC are the origin of melanocytes from the neural crest [15], and the strong analogies of EVMM with the migration of stem cells from the neural crest along the abluminal side of vessels during a part of their journey in the embryo [16,17]. In addition, the pericytic location of angiotropic MC provides support for the mesenchymal stemness of this population of MC.…”