Dissecting early regulatory relationships in the lamprey neural crest gene network

Division of Biology, California Institute of Technology, Pasadena, CA 81125, USA.
Proceedings of the National Academy of Sciences (Impact Factor: 9.67). 01/2009; 105(51):20083-8. DOI: 10.1073/pnas.0806009105
Source: PubMed


The neural crest, a multipotent embryonic cell type, originates at the border between neural and nonneural ectoderm. After neural tube closure, these cells undergo an epithelial-mesenchymal transition, migrate to precise, often distant locations, and differentiate into diverse derivatives. Analyses of expression and function of signaling and transcription factors in higher vertebrates has led to the proposal that a neural crest gene regulatory network (NC-GRN) orchestrates neural crest formation. Here, we interrogate the NC-GRN in the lamprey, taking advantage of its slow development and basal phylogenetic position to resolve early inductive events, 1 regulatory step at the time. To establish regulatory relationships at the neural plate border, we assess relative expression of 6 neural crest network genes and effects of individually perturbing each on the remaining 5. The results refine an upstream portion of the NC-GRN and reveal unexpected order and linkages therein; e.g., lamprey AP-2 appears to function early as a neural plate border rather than a neural crest specifier and in a pathway linked to MsxA but independent of ZicA. These findings provide an ancestral framework for performing comparative tests in higher vertebrates in which network linkages may be more difficult to resolve because of their rapid development.

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Available from: Natalya Nikitina, Jan 13, 2014
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    • "of proteins and a well known neural plate border specifier, also expressed in the neural plate border region and in the anterior ectoderm region containing placodal progenitors (Khudyakov et al., 2009). Much of the information about the role of Zic1 in the neural crest gene regulatory network comes from experiments performed in frog and lamprey (Sato et al., 2012; Nikitina et al., 2008). The finding that loss of cMyb results in upregulation of Zic1 in the cranial neural folds raises the intriguing possibility that cMyb may normally function to repress Zic1 expression in the head. "
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    ABSTRACT: The transcription factor cMyb has well known functions in vertebrate hematopoiesis, but little was known about its distribution or function at early developmental stages. Here, we show that cMyb transcripts are present at the neural plate during gastrulation in chick embryos. cMyb expression then resolves to the cranial neural folds and is maintained in early migrating cranial neural crest cells during and after neurulation. Morpholino-mediated knock-down of cMyb reduces expression of Pax7 and Twist at the neural plate border, as well as reducing expression of neural crest specifier genes Snail2 and Sox10 and completely eliminating expression of Ets1. On the other hand, its loss results in abnormal maintenance of Zic1, but little or no effect on other neural crest specifier genes like FoxD3 or Sox9. These results place cMyb in a critical hierarchical position within the cranial neural crest cell gene regulatory network, likely directly inhibiting Zic1 and upstream of Ets1 and some, but not all, neural crest specifier genes.
    Mechanisms of development 02/2014; 132(1). DOI:10.1016/j.mod.2014.01.005 · 2.44 Impact Factor
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    • "pax3 Bang et al., 1999 Matsunaga et al., 2001 Goulding et al., 1991 Sauka-Spengler et al., 2007; Nikitina et al., 2008 Thomas et al., 2008, Betters et al., 2010 "
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    ABSTRACT: The neural crest is a transient and multipotent cell population arising at the edge of the neural plate in vertebrates. Recent findings highlight that neural crest patterning is initiated during gastrulation, i.e. earlier than classically described, in a progenitor domain named the neural border. This chapter reviews the dynamic and complex molecular interactions underlying neural border formation and neural crest emergence.
    Developmental Biology 01/2012; 366(1):22-33. DOI:10.1016/j.ydbio.2012.01.013 · 3.55 Impact Factor
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    • "For example, knock-down of over eight transcription factors operating either at the neural plate border or in the neural crest specifier module suggests conserved functions of these genes in lamprey compared with those operating in jawed vertebrates (Sauka-Spengler et al., 2007). Indeed, fine tuned analysis of interconnections in the neural plate border module of lamprey (Nikitina et al, 2008) reveals remarkably similar connections to those observed in Xenopus (deCroze et al., 2011; see Monsoro-Burq Chapter). "
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    ABSTRACT: The neural crest is a multipotent and migratory cell type that forms transiently in the developing vertebrate embryo. These cells emerge from the central nervous system, migrate extensively and give rise to diverse cell lineages including melanocytes, craniofacial cartilage and bone, peripheral and enteric neurons and glia, and smooth muscle. A vertebrate innovation, the gene regulatory network underlying neural crest formation appears to be highly conserved, even to the base of vertebrates. Here, we present an overview of important concepts in the neural crest field dating from its discovery 150 years ago to open questions that will motivate future research.
    Developmental Biology 01/2012; 366(1):2-9. DOI:10.1016/j.ydbio.2011.12.042 · 3.55 Impact Factor
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