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: 9.81). 01/2009; 105(51):20083-8. DOI: 10.1073/pnas.0806009105
Source: PubMed

ABSTRACT 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.

Download full-text


Available from: Natalya Nikitina, Jan 13, 2014
  • Source
    • "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 "
    [Show abstract] [Hide abstract]
    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 · 3.64 Impact Factor
  • Source
    • "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). "
    [Show abstract] [Hide abstract]
    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 · 3.64 Impact Factor
  • Source
    • "In zebrafish, loss of tfap2a results in apoptosis of neural crest progenitors, leading to defects in neural crest derivatives, including posterior pharyngeal arches, pigment cells, enteric neurons, and dorsal root ganglia (Barrallo-Gimeno et al., 2004; Knight et al., 2003; O'Brien et al., 2004). A role for tfap2a in neural crest induction has also been proposed in Xenopus (de Crozé et al., 2011; Luo et al., 2003), and in Lamprey, ap2a was shown to act in the induction of the neural plate border (Nikitina et al., 2008). Foxd3, a member of the Forkhead transcription factor family, has multiple functions during embryonic development. "
    [Show abstract] [Hide abstract]
    ABSTRACT: The neural crest is a stem cell-like population exclusive to vertebrates that gives rise to many different cell types including chondrocytes, neurons and melanocytes. Arising from the neural plate border at the intersection of Wnt and Bmp signaling pathways, the complexity of neural crest gene regulatory networks has made the earliest steps of induction difficult to elucidate. Here, we report that tfap2a and foxd3 participate in neural crest induction and are necessary and sufficient for this process to proceed. Double mutant tfap2a (mont blanc, mob) and foxd3 (mother superior, mos) mob;mos zebrafish embryos completely lack all neural crest-derived tissues. Moreover, tfap2a and foxd3 are expressed during gastrulation prior to neural crest induction in distinct, complementary, domains; tfap2a is expressed in the ventral non-neural ectoderm and foxd3 in the dorsal mesendoderm and ectoderm. We further show that Bmp signaling is expanded in mob;mos embryos while expression of dkk1, a Wnt signaling inhibitor, is increased and canonical Wnt targets are suppressed. These changes in Bmp and Wnt signaling result in specific perturbations of neural crest induction rather than general defects in neural plate border or dorso-ventral patterning. foxd3 overexpression, on the other hand, enhances the ability of tfap2a to ectopically induce neural crest around the neural plate, overriding the normal neural plate border limit of the early neural crest territory. Although loss of either Tfap2a or Foxd3 alters Bmp and Wnt signaling patterns, only their combined inactivation sufficiently alters these signaling gradients to abort neural crest induction. Collectively, our results indicate that tfap2a and foxd3, in addition to their respective roles in the differentiation of neural crest derivatives, also jointly maintain the balance of Bmp and Wnt signaling in order to delineate the neural crest induction domain.
    Developmental Biology 09/2011; 360(1):173-85. DOI:10.1016/j.ydbio.2011.09.019 · 3.64 Impact Factor
Show more