The winged-helix transcription factor FoxD3 is important for establishing the neural crest lineage and repressing melanogenesis in avian embryos

Development ◽  
2001 ◽  
Vol 128 (8) ◽  
pp. 1467-1479 ◽  
Author(s):  
R. Kos ◽  
M.V. Reedy ◽  
R.L. Johnson ◽  
C.A. Erickson
Keyword(s):  
Transcription Factors ◽  
Neural Crest ◽  
Antisense Oligonucleotides ◽  
Neural Crest Cells ◽  
Winged Helix ◽  
Dorsal Neural Tube ◽  
Neural Crest Development ◽  
Mesenchymal Transformation ◽  
Winged Helix Transcription Factor

The winged-helix or forkhead class of transcription factors has been shown to play important roles in cell specification and lineage segregation. We have cloned the chicken homolog of FoxD3, a member of the winged-helix class of transcription factors, and analyzed its expression. Based on its expression in the dorsal neural tube and in all neural crest lineages except the late-emigrating melanoblasts, we predicted that FoxD3 might be important in the segregation of the neural crest lineage from the neural epithelium, and for repressing melanogenesis in early-migrating neural crest cells. Misexpression of FoxD3 by electroporation in the lateral neural epithelium early in neural crest development produced an expansion of HNK1 immunoreactivity throughout the neural epithelium, although these cells did not undergo an epithelial/mesenchymal transformation. To test whether FoxD3 represses melanogenesis in early migrating neural crest cells, we knocked down expression in cultured neural crest with antisense oligonucleotides and in vivo by treatment with morpholino antisense oligonucleotides. Both experimental approaches resulted in an expansion of the melanoblast lineage, probably at the expense of neuronal and glial lineages. Conversely, persistent expression of FoxD3 in late-migrating neural crest cells using RCAS viruses resulted in the failure of melanoblasts to develop. We suggest that FoxD3 plays two important roles in neural crest development. First, it is involved in the segregation of the neural crest lineage from the neuroepithelium. Second, it represses melanogenesis, thereby allowing other neural crest derivatives to differentiate during the early stages of neural crest patterning.

scholarly journals Bimodal function of chromatin remodeler Hmga1 in neural crest induction and Wnt-dependent emigration

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Shashank Gandhi ◽  
Erica J Hutchins ◽  
Krystyna Maruszko ◽  
Jong H Park ◽  
Matthew Thomson ◽  
...  
Keyword(s):  
Neural Crest ◽  
Neural Tube ◽  
Neural Crest Cells ◽  
Neural Plate ◽  
Chromatin Remodeler ◽  
Lineage Specification ◽  
Dorsal Neural Tube ◽  
Neural Crest Development ◽  
Neural Plate Border ◽  
Canonical Wnt

During gastrulation, neural crest cells are specified at the neural plate border, as characterized by Pax7 expression. Using single-cell RNA sequencing coupled with high-resolution in situ hybridization to identify novel transcriptional regulators, we show that chromatin remodeler Hmga1 is highly expressed prior to specification and maintained in migrating chick neural crest cells. Temporally controlled CRISPR-Cas9-mediated knockouts uncovered two distinct functions of Hmga1 in neural crest development. At the neural plate border, Hmga1 regulates Pax7-dependent neural crest lineage specification. At premigratory stages, a second role manifests where Hmga1 loss reduces cranial crest emigration from the dorsal neural tube independent of Pax7. Interestingly, this is rescued by stabilized ß-catenin, thus implicating Hmga1 as a canonical Wnt activator. Together, our results show that Hmga1 functions in a bimodal manner during neural crest development to regulate specification at the neural plate border, and subsequent emigration from the neural tube via canonical Wnt signaling.

scholarly journals Lineage-specific requirements of β-catenin in neural crest development

2002 ◽  
Vol 159 (5) ◽  
pp. 867-880 ◽  
Author(s):  
Lisette Hari ◽  
Véronique Brault ◽  
Maurice Kléber ◽  
Hye-Youn Lee ◽  
Fabian Ille ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Neural Crest ◽  
Neural Crest Cells ◽  
Neural Crest Stem Cells ◽  
Downstream Signaling ◽  
Neural Crest Development ◽  
Sensory Neurogenesis

β-Catenin plays a pivotal role in cadherin-mediated cell adhesion. Moreover, it is a downstream signaling component of Wnt that controls multiple developmental processes such as cell proliferation, apoptosis, and fate decisions. To study the role of β-catenin in neural crest development, we used the Cre/loxP system to ablate β-catenin specifically in neural crest stem cells. Although several neural crest–derived structures develop normally, mutant animals lack melanocytes and dorsal root ganglia (DRG). In vivo and in vitro analyses revealed that mutant neural crest cells emigrate but fail to generate an early wave of sensory neurogenesis that is normally marked by the transcription factor neurogenin (ngn) 2. This indicates a role of β-catenin in premigratory or early migratory neural crest and points to heterogeneity of neural crest cells at the earliest stages of crest development. In addition, migratory neural crest cells lateral to the neural tube do not aggregate to form DRG and are unable to produce a later wave of sensory neurogenesis usually marked by the transcription factor ngn1. We propose that the requirement of β-catenin for the specification of melanocytes and sensory neuronal lineages reflects roles of β-catenin both in Wnt signaling and in mediating cell–cell interactions.

Regulation of the onset of neural crest migration by coordinated activity of BMP4 and Noggin in the dorsal neural tube

Development ◽  
1999 ◽  
Vol 126 (21) ◽  
pp. 4749-4762 ◽  
Author(s):  
D. Sela-Donenfeld ◽  
C. Kalcheim
Keyword(s):  
Neural Crest ◽  
Neural Tube ◽  
Specific Inhibitor ◽  
Neural Crest Cells ◽  
Concomitant Treatment ◽  
Neural Tubes ◽  
Dorsal Neural Tube ◽  
Dependent Inhibition ◽  
Neural Crest Migration

For neural crest cells to engage in migration, it is necessary that epithelial premigratory crest cells convert into mesenchyme. The mechanisms that trigger cell delamination from the dorsal neural tube remain poorly understood. We find that, in 15- to 40-somite-stage avian embryos, BMP4 mRNA is homogeneously distributed along the longitudinal extent of the dorsal neural tube, whereas its specific inhibitor noggin exists in a gradient of expression that decreases caudorostrally. This rostralward reduction in signal intensity coincides with the onset of emigration of neural crest cells. Hence, we hypothesized that an interplay between Noggin and BMP4 in the dorsal tube generates graded concentrations of the latter that in turn triggers the delamination of neural crest progenitors. Consistent with this suggestion, disruption of the gradient by grafting Noggin-producing cells dorsal to the neural tube at levels opposite the segmental plate or newly formed somites, inhibited emigration of HNK-1-positive crest cells, which instead accumulated within the dorsal tube. Similar results were obtained with explanted neural tubes from the same somitic levels exposed to Noggin. Exposure to Follistatin, however, had no effect. The Noggin-dependent inhibition was overcome by concomitant treatment with BMP4, which when added alone, also accelerated cell emigration compared to untreated controls. Furthermore, the observed inhibition of neural crest emigration in vivo was preceded by a partial or total reduction in the expression of cadherin-6B and rhoB but not in the expression of slug mRNA or protein. Altogether, these results suggest that a coordinated activity of Noggin and BMP4 in the dorsal neural tube triggers delamination of specified, slug-expressing neural crest cells. Thus, BMPs play multiple and discernible roles at sequential stages of neural crest ontogeny, from specification through delamination and later differentiation of specific neural crest derivatives.

The winged-helix transcription factor Foxd3 suppresses interneuron differentiation and promotes neural crest cell fate

Development ◽  
2001 ◽  
Vol 128 (21) ◽  
pp. 4127-4138 ◽  
Author(s):  
Mirella Dottori ◽  
Michael K. Gross ◽  
Patricia Labosky ◽  
Martyn Goulding
Keyword(s):  
Transcription Factor ◽  
Neural Crest ◽  
Cell Fate ◽  
Neural Tube ◽  
Neural Crest Cell ◽  
Neural Crest Cells ◽  
Cell Types ◽  
Winged Helix ◽  
Multiple Cell ◽  
Winged Helix Transcription Factor

The neural crest is a migratory cell population that gives rise to multiple cell types in the vertebrate embryo. The intrinsic determinants that segregate neural crest cells from multipotential dorsal progenitors within the neural tube are poorly defined. In this study, we show that the winged helix transcription factor Foxd3 is expressed in both premigratory and migratory neural crest cells. Foxd3 is genetically downstream of Pax3 and is not expressed in regions of Pax3 mutant mice that lack neural crest, implying that Foxd3 may regulate aspects of the neural crest differentiation program. We show that misexpression of Foxd3 in the chick neural tube promotes a neural crest-like phenotype and suppresses interneuron differentiation. Cells that ectopically express Foxd3 upregulate HNK1 and Cad7, delaminate and emigrate from the neural tube at multiple dorsoventral levels. Foxd3 does not induce Slug and RhoB, nor is its ability to promote a neural crest-like phenotype enhanced by co-expression of Slug. Together these results suggest Foxd3 can function independently of Slug and RhoB to promote the development of neural crest cells from neural tube progenitors.

scholarly journals In vivo transplantation of mammalian neural crest cells into chick hosts reveals a new autonomic sublineage restriction

Development ◽  
1999 ◽  
Vol 126 (19) ◽  
pp. 4351-4363 ◽  
Author(s):  
P.M. White ◽  
D.J. Anderson
Keyword(s):  
Neural Crest ◽  
Neural Crest Cells ◽  
Parasympathetic Ganglia ◽  
Neuronal Markers ◽  
Neural Crest Development ◽  
Parasympathetic Neurons ◽  
Neuronal Subtype ◽  
Transplantation System ◽  
Satellite Glia

The study of mammalian neural crest development has been limited by the lack of an accessible system for in vivo transplantation of these cells. We have developed a novel transplantation system to study lineage restriction in the rodent neural crest. Migratory rat neural crest cells (NCCs), transplanted into chicken embryos, can differentiate into sensory, sympathetic, and parasympathetic neurons, as shown by the expression of neuronal subtype-specific and pan-neuronal markers, as well as into Schwann cells and satellite glia. In contrast, an immunopurified population of enteric neural precursors (ENPs) from the fetal gut can also generate neurons in all of these ganglia, but only expresses appropriate neuronal subtype markers in Remak's and associated pelvic parasympathetic ganglia. ENPs also appear restricted in the kinds of glia they can generate in comparison to NCCs. Thus ENPs have parasympathetic and presumably enteric capacities, but not sympathetic or sensory capacities. These results identify a new autonomic lineage restriction in the neural crest, and suggest that this restriction preceeds the choice between neuronal and glial fates.

scholarly journals GSK3 Controls Migration of the Neural Crest Lineage

2018 ◽  
Author(s):  
Sandra G. Gonzalez Malagon ◽  
Anna M. Lopez Muñoz ◽  
Daniel Doro ◽  
Triòna G. Bolger ◽  
Evon Poon ◽  
...  
Keyword(s):  
Cell Migration ◽  
Neural Crest ◽  
Glycogen Synthase ◽  
Neuroblastoma Cells ◽  
Neural Crest Cells ◽  
Anaplastic Lymphoma ◽  
Neural Crest Development ◽  
And Migration ◽  
Neural Crest Migration

AbstractMigration of the neural crest lineage is critical to its physiological function. Mechanisms controlling neural crest migration are comparatively unknown, due to difficulties accessing this cell population in vivo. Here, we uncover novel requirements of glycogen synthase kinase 3 (GSK3) in regulating the neural crest. We demonstrate that GSK3 is tyrosine phosphorylated (pY) in neural crest cells and that this activation depends on anaplastic lymphoma kinase (ALK), a protein associated with neuroblastoma. Consistent with this, neuroblastoma cells with pathologically increased ALK activity express high levels of pY-GSK3 and migration of these cells can be inhibited by GSK3 or ALK blockade. In normal neural crest cells, loss of GSK3 leads to increased pFAK and misregulation of Rac1 and lamellipodin, key regulators of cell migration. Genetic reduction of GSK-3 results in failure of migration. All together, this work identifies a role for GSK3 in cell migration during neural crest development and cancer.

The dorsal neural tube organizes the dermamyotome and induces axial myocytes in the avian embryo

Development ◽  
1996 ◽  
Vol 122 (1) ◽  
pp. 231-241 ◽  
Author(s):  
M.S. Spence ◽  
J. Yip ◽  
C.A. Erickson
Keyword(s):  
Neural Crest ◽  
Neural Tube ◽  
Neural Crest Cells ◽  
Intervertebral Discs ◽  
Paraxial Mesoderm ◽  
Avian Embryo ◽  
Dorsal Neural Tube ◽  
Ventral Neural Tube ◽  
Dorsal Ectoderm

Somites, like all axial structures, display dorsoventral polarity. The dorsal portion of the somite forms the dermamyotome, which gives rise to the dermis and axial musculature, whereas the ventromedial somite disperses to generate the sclerotome, which later comprises the vertebrae and intervertebral discs. Although the neural tube and notochord are known to regulate some aspects of this dorsoventral pattern, the precise tissues that initially specify the dermamyotome, and later the myotome from it, have been controversial. Indeed, dorsal and ventral neural tube, notochord, ectoderm and neural crest cells have all been proposed to influence dermamyotome formation or to regulate myocyte differentiation. In this report we describe a series of experimental manipulations in the chick embryo to show that dermamyotome formation is regulated by interactions with the dorsal neural tube. First, we demonstrate that when a neural tube is rotated 180 degrees around its dorsoventral axis, a secondary dermamyotome is induced from what would normally have developed as sclerotome. Second, if we ablate the dorsal neural tube, dermamyotomes are absent in the majority of embryos. Third, if we graft pieces of dorsal neural tube into a ventral position between the notochord and ventral somite, a dermamyotome develops from the sclerotome that is proximate to the graft, and myocytes differentiate. In addition, we also show that myogenesis can be regulated by the dorsal neural tube because when pieces of dorsal neural tube and unsegmented paraxial mesoderm are combined in tissue culture, myocytes differentiate, whereas mesoderm cultures alone do not produce myocytes autonomously. In all of the experimental perturbations in vivo, the dorsal neural tube induced dorsal structures from the mesoderm in the presence of notochord and floorplate, which have been reported previously to induce sclerotome. Thus, we have demonstrated that in the context of the embryonic environment, a dorsalizing signal from the dorsal neural tube can compete with the diffusible ventralizing signal from the notochord. In contrast to dorsal neural tube, pieces of ventral neural tube, dorsal ectoderm or neural crest cells, all of which have been postulated to control dermamyotome formation or to induce myogenesis, either fail to do so or provoke only minimal inductive responses in any of our assays. However, complicating the issue, we find consistent with previous studies that following ablation of the entire neural tube, dermamyotome formation still proceeds adjacent to the dorsal ectoderm. Together these results suggest that, although dorsal ectoderm may be less potent than the dorsal neural tube in inducing dermamyotome, it does nonetheless possess some dermamyotomal-inducing activity. Based on our data and that of others, we propose a model for somite dorsoventral patterning in which competing diffusible signals from the dorsal neural tube and from the notochord/floorplate specify dermamyotome and sclerotome, respectively. In our model, the positioning of the dermamyotome dorsally is due to the absence or reduced levels of the notochord-derived ventralizing signals, as well as to the presence of dominant dorsalizing signals. These dorsal signals are possibly localized and amplified by binding to the basal lamina of the ectoderm, where they can signal the underlying somite, and may also be produced by the ectoderm as well.

scholarly journals Cancer-associated HIF-2α impacts trunk neural crest stemness

2020 ◽  
Author(s):  
Sofie Mohlin ◽  
Camilla U. Persson ◽  
Elina Fredlund ◽  
Emanuela Monni ◽  
Jessica M. Lindvall ◽  
...  
Keyword(s):  
Neural Crest ◽  
Normal Development ◽  
Hypoxia Inducible Factor ◽  
Neural Crest Cells ◽  
Sympathetic Ganglia ◽  
Stem Cell Population ◽  
Neural Crest Development ◽  
Trunk Neural Crest

AbstractThe neural crest is a stem cell population that gives rise to sympathetic ganglia, the cell type of origin of neuroblastoma. Hypoxia Inducible Factor (HIF)-2α is associated with high risk neuroblastoma, however, little is known about its role in normal neural crest development. To address this important question, here we show that HIF-2α is expressed in trunk neural crest cells of human, murine and avian embryos. Modulating HIF-2α in vivo not only causes developmental delays but also induces proliferation and stemness of neural crest cells while altering the number of cells migrating ventrally to sympathoadrenal sites. Transcriptome changes after loss of HIF-2α reflect the in vivo phenotype. The results suggest that expression levels of HIF-2α must be strictly controlled and abnormal levels increase stemness and may promote metastasis. Our findings help elucidate the role of HIF-2α during normal development with implications also in tumor initiation at the onset of neuroblastoma.

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