Current perspectives of the signaling pathways directing neural crest induction

Abstract

The neural crest is a migratory population of embryonic cells with a tremendous potential to differentiate and contribute to nearly every organ system in the adult body. Over the past two decades, an incredible amount of research has given us a reasonable understanding of how these cells are generated. Neural crest induction involves the combinatorial input of multiple signaling pathways and transcription factors, and is thought to occur in two phases from gastrulation to neurulation. In the first phase, FGF and Wnt signaling induce NC progenitors at the border of the neural plate, activating the expression of members of the Msx, Pax, and Zic families, among others. In the second phase, BMP, Wnt, and Notch signaling maintain these progenitors and bring about the expression of definitive NC markers including Snail2, FoxD3, and Sox9/10. In recent years, additional signaling molecules and modulators of these pathways have been uncovered, creating an increasingly complex regulatory network. In this work, we provide a comprehensive review of the major signaling pathways that participate in neural crest induction, with a focus on recent developments and current perspectives. We provide a simplified model of early neural crest development and stress similarities and differences between four major model organisms: Xenopus, chick, zebrafish, and mouse.

Dosage changes of MED13L further delineate its role in congenital heart defects and intellectual disability

“…2,3 Animal studies imply a specific role for MED13, similar in size and B50% identical to MED13L, in regulating transcription of Wnt and Notch target genes, and Hh signal transduction, [18][19][20] which are involved in neural crest induction. 21 Neural crest cell migration has an important role in the development of the heart, the nervous system and the facial mesenchyme, which could explain the syndromic signs of MED13L haploinsufficiency and the clinical overlap with DiGeorge Figure 2 Copy number variants of MED13L in our patients. Patient 1 (DECIPHER no.…”

“…The third patient is a girl born 5 days preterm with a history of transient but marked fetal hydrops during pregnancy (weeks [16][17][18][19][20][21][22][23][24][25]. Her birth weight was 2200 g (o3rd centile) and the length was 47 cm (3rd centile).…”

The Proto-oncogene Transcription Factor Ets1 Regulates Neural Crest Development through Histone Deacetylase 1 to Mediate Output of Bone Morphogenetic Protein Signaling

“…Arising at the border between neural plate and non-neural ectoderm, NC cells migrate extensively and differentiate into various tissues (1). The initial induction of NC occurs during gastrulation in response to the combined effects of bone morphogenetic protein (BMP), Wnt, FGF, retinoic acid, and Notch signals (2)(3)(4)(5)(6). These signaling pathways orchestrate and firstly activate neural plate border (NPB) specifiers including Pax3, Msx1 (7), and Zic1 (8), which establish a broad competence domain at the NPB.…”

GSK3 Inhibitors Regulate MYCN mRNA Levels and Reduce Neuroblastoma Cell Viability through Multiple Mechanisms, Including p53 and Wnt Signaling

“…GSK3 is known to be involved in a large number of signaling pathways [e.g., Wnt, Shh, receptor tyrosine kinase, Notch, mTOR, insulin, PI3K/Akt, mitogen-activated protein kinase (MAPK), and p53], many of which are associated with the neural crest (10,11). Canonical Wnt signaling, in particular, is known to be heavily involved in the induction, delamination, and differentiation of the neural crest (11,12), and GSK3 is a key negative mediator of Wnt signaling. GSK3 is a master regulator of neural progenitor homeostasis, integrating multiple proliferation, and differentiation signals (13).…”