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

Abstract

The peripheral nervous system (PNS) of higher vertebrates is segmented to align the spinal nerve roots with the vertebrae. This copatterning is set up during embryogenesis, when vertebrae develop from the sclerotome layer of the metameric somites, and PNS neurons and glia differentiate from neural crest cells (NCCs) that preferentially migrate into the anterior sclerotome halves. Previous analyses of mice deficient in the class 3 semaphorin (SEMA3) receptors neuropilin (NRP) 1 or 2 raised the possibility that each controlled a distinct aspect of trunk NCC migration. We now demonstrate that both pathways act sequentially in distinct NCC subpopulations and thereby cooperate to enforce segmental NCC migration. Specifically, SEMA3A/NRP1 signalling first directs one population of NCCs from the intersomitic path into the sclerotome, and SEMA3F/NRP2 signalling acts subsequently to restrict a second population to the anterior half of the sclerotome. NCC exclusion from either the posterior sclerotome or the intersomitic boundary is sufficient to enforce the separation of neighbouring NCC streams and the segregation of sensory NCC progeny into metameric dorsal root ganglia (DRG). By contrast, the combined loss of both guidance pathways leads to ectopic invasion of the intersomitic furrows and posterior sclerotome halves, disrupting metameric NCC streaming and DRG segmentation.

NRP1 acts cell autonomously in endothelium to promote tip cell function during sprouting angiogenesis

“…10,14,18,[34][35][36] We have shown here that NRP1 expression by neural progenitors and macrophages is not required for brain angiogenesis, even though these cell types interact with angiogenic endothelium and can therefore present NRP1 in trans (Figures 1, 3, and 4). It is therefore likely that the ability of NRP1 to interact heterotypically with VEGFR2 in tissue culture models 9 and homophilically in biochemical assays 37 is not important for physiological angiogenesis, at least during brain vascular development.…”

Class 3 semaphorins: physiological vascular normalizing agents for anti‐cancer therapy

“…In addition, it has been reported that the a1 domain of Nrps binds to the sema domain of Sema3 at low [65] or high affinity [68,69], whereas deletion of Nrp1 a1/a2 domains does not affect full-length Sema3A binding [67]. However, the observation that knock-in mice carrying point mutations in the Nrp1 a1 domain display several defective neuronal and non-neuronal phenotypes is consistent with a lack of Sema3A activity [70][71][72][73][74][75][76][77], and clearly indicates that the a1 domain of Nrp1 is required for [193,194] GBM DC101 ↓ Microvessel density, ↑ PVC coverage ↓ basement membrane (↓ collagen IV), ↓ tortuosity and diameter, ↑ oxygenation [195] Fibrosarcoma, squamous carcinoma, NSCLC…”

Notch signaling regulates the differentiation of neural crest from human pluripotent stem cells

“…Protocols to derive neural crest cells from hPSCs are available (Lee et al, 2007;Menendez et al, 2011), but they produce migratory neural crest cells [marked by the expression of p75 (also known as NGFR) and HNK1 (also known as CD57 and B3GAT1)]. Both premigratory and migratory neural crest cells are able to generate neuronal and non-neuronal descendants (Bronner-Fraser and Fraser, 1989;Bronner-Fraser and Fraser, 1988); however, migratory neural crest cells will undergo progressive lineage specification towards terminally differentiated cell types, which might restrict their usefulness for research purposes (Hari et al, 2012;Schwarz et al, 2009). Therefore, premigratory neural crest cells would be ideal for studying the signaling pathways that control the specification of neural crest fate.…”