scholarly journals Building the Border: Development of the Chordate Neural Plate Border Region and Its Derivatives

2020 ◽  
Vol 11 ◽  
Author(s):  
Ankita Thawani ◽  
Andrew K. Groves
Keyword(s):  
Neural Crest ◽  
Signaling Pathways ◽  
Regulatory Networks ◽  
Neural Plate ◽  
Bmp Signaling ◽  
Border Region ◽  
Thin Strip ◽  
Morphogenetic Protein ◽  
Neural Plate Border ◽  
Spatio Temporal

The paired cranial sensory organs and peripheral nervous system of vertebrates arise from a thin strip of cells immediately adjacent to the developing neural plate. The neural plate border region comprises progenitors for four key populations of cells: neural plate cells, neural crest cells, the cranial placodes, and epidermis. Putative homologues of these neural plate border derivatives can be found in protochordates such as amphioxus and tunicates. In this review, we summarize key signaling pathways and transcription factors that regulate the inductive and patterning events at the neural plate border region that give rise to the neural crest and placodal lineages. Gene regulatory networks driven by signals from WNT, fibroblast growth factor (FGF), and bone morphogenetic protein (BMP) signaling primarily dictate the formation of the crest and placodal lineages. We review these studies and discuss the potential of recent advances in spatio-temporal transcriptomic and epigenomic analyses that would allow a mechanistic understanding of how these signaling pathways and their downstream transcriptional cascades regulate the formation of the neural plate border region.

scholarly journals Review: The Role of Wnt/β-Catenin Signalling in Neural Crest Development in Zebrafish

2021 ◽  
Vol 9 ◽  
Author(s):  
Gemma Sutton ◽  
Robert N. Kelsh ◽  
Steffen Scholpp
Keyword(s):  
Neural Crest ◽  
Pigment Cell ◽  
Model Organism ◽  
Neural Plate ◽  
The Body ◽  
Signalling Pathway ◽  
Border Region ◽  
Pigment Cells ◽  
Neural Plate Border

The neural crest (NC) is a multipotent cell population in vertebrate embryos with extraordinary migratory capacity. The NC is crucial for vertebrate development and forms a myriad of cell derivatives throughout the body, including pigment cells, neuronal cells of the peripheral nervous system, cardiomyocytes and skeletogenic cells in craniofacial tissue. NC induction occurs at the end of gastrulation when the multipotent population of NC progenitors emerges in the ectodermal germ layer in the neural plate border region. In the process of NC fate specification, fate-specific markers are expressed in multipotent progenitors, which subsequently adopt a specific fate. Thus, NC cells delaminate from the neural plate border and migrate extensively throughout the embryo until they differentiate into various cell derivatives. Multiple signalling pathways regulate the processes of NC induction and specification. This review explores the ongoing role of the Wnt/β-catenin signalling pathway during NC development, focusing on research undertaken in the Teleost model organism, zebrafish (Danio rerio). We discuss the function of the Wnt/β-catenin signalling pathway in inducing the NC within the neural plate border and the specification of melanocytes from the NC. The current understanding of NC development suggests a continual role of Wnt/β-catenin signalling in activating and maintaining the gene regulatory network during NC induction and pigment cell specification. We relate this to emerging models and hypotheses on NC fate restriction. Finally, we highlight the ongoing challenges facing NC research, current gaps in knowledge, and this field’s potential future directions.

scholarly journals Regulation of BMP Signaling by O-GlcNAcylation

2019 ◽  
Author(s):  
Matthew Moulton ◽  
Greg Humphreys ◽  
Alexander Kim ◽  
Anthea Letsou
Keyword(s):  
Signal Transduction ◽  
Embryonic Development ◽  
Signaling Pathways ◽  
Bmp Signaling ◽  
Type I ◽  
Morphogenetic Protein ◽  
Sex Combs ◽  
Receptor Like Kinase ◽  
Dietary Sugar ◽  
Spatio Temporal

SummaryPrecise regulation of signal transduction is critical throughout organismal life, both for embryonic development and for adult homeostasis. To ensure proper spatio-temporal signal transduction, Bone Morphogenetic Protein (BMP) signaling pathways, like all other signaling pathways, are regulated by both agonists and antagonists. Here, we report identification of a previously unrecognized method of signal antagonism for Dpp (Decapentaplegic), a Drosophila BMP family member. We demonstrate that the BMP type I receptor Saxophone (Sax) functions as a Dpp receptor in the Drosophila embryonic epidermis, but that its activity is normally inhibited by the O-linked glycosyltransferase Super sex combs (Sxc). In wild-type embryos, inhibition of Saxophone (Sax) activity in the epidermis marks the BMP type I receptor Thickveins (Tkv) as the sole conduit for Dpp. In contrast, in sxc mutants, the Dpp signal is transduced by both Tkv and Sax, and elevated Dpp signaling induces errors in embryonic development that lead to embryonic death. We also demonstrate that Sax is the O-glycosylated target of Sxc and that O-glycosylation of Sax can be modulated by dietary sugar. Together, these findings link fertility to nutritive environment and point to Sax (activin receptor-like kinase 2 [ACVR1 or ALK2]) signaling as the nutrient-sensitive branch of BMP signaling.Graphical Abstract

scholarly journals Xenopus Nkx6.3 Is a Neural Plate Border Specifier Required for Neural Crest Development

PLoS ONE ◽  
2014 ◽  
Vol 9 (12) ◽  
pp. e115165 ◽  
Author(s):  
Zuming Zhang ◽  
Yu Shi ◽  
Shuhua Zhao ◽  
Jiejing Li ◽  
Chaocui Li ◽  
...  
Keyword(s):  
Neural Crest ◽  
Neural Plate ◽  
Neural Crest Development ◽  
Neural Plate Border

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 BMP action in skeletogenesis involves attenuation of retinoid signaling

2006 ◽  
Vol 174 (1) ◽  
pp. 101-113 ◽  
Author(s):  
Lisa M. Hoffman ◽  
Kamal Garcha ◽  
Konstantina Karamboulas ◽  
Matthew F. Cowan ◽  
Linsay M. Drysdale ◽  
...  
Keyword(s):  
Retinoic Acid ◽  
Organ Culture ◽  
Signaling Pathways ◽  
Bone Morphogenetic Protein ◽  
Signaling Pathway ◽  
Signaling Molecules ◽  
Bmp Signaling ◽  
Retinoid Signaling ◽  
Morphogenetic Protein ◽  
Bona Fide

The bone morphogenetic protein (BMP) and growth and differentiation factor (GDF) signaling pathways have well-established and essential roles within the developing skeleton in coordinating the formation of cartilaginous anlagen. However, the identification of bona fide targets that underlie the action of these signaling molecules in chondrogenesis has remained elusive. We have identified the gene for the retinoic acid (RA) synthesis enzyme Aldh1a2 as a principal target of BMP signaling; prochondrogenic BMPs or GDFs lead to attenuation of Aldh1a2 expression and, consequently, to reduced activation of the retinoid signaling pathway. Consistent with this, antagonism of retinoid signaling phenocopies BMP4 action, whereas RA inhibits the chondrogenic stimulatory activity of BMP4. BMP4 also down-regulates Aldh1a2 expression in organ culture and, consistent with this, Aldh1a2 is actively excluded from the developing cartilage anlagens. Collectively, these findings provide novel insights into BMP action and demonstrate that BMP signaling governs the fate of prechondrogenic mesenchyme, at least in part, through regulation of retinoid signaling.

scholarly journals Ectopic Hedgehog Signaling Causes Cleft Palate and Defective Osteogenesis

2018 ◽  
Vol 97 (13) ◽  
pp. 1485-1493 ◽  
Author(s):  
N.L. Hammond ◽  
K.J. Brookes ◽  
M.J. Dixon
Keyword(s):  
Cleft Palate ◽  
Hedgehog Signaling ◽  
Regulatory Networks ◽  
Neural Crest Cell ◽  
Bmp Signaling ◽  
The Novel ◽  
Morphogenetic Protein ◽  
Secondary Palate ◽  
Hh Signaling ◽  
Crest Cell

Cleft palate is a common birth defect that frequently occurs in human congenital malformations caused by mutations in components of the Sonic Hedgehog (S HH) signaling cascade. Shh is expressed in dynamic, spatiotemporal domains within epithelial rugae and plays a key role in driving epithelial-mesenchymal interactions that are central to development of the secondary palate. However, the gene regulatory networks downstream of Hedgehog (Hh) signaling are incompletely characterized. Here, we show that ectopic Hh signaling in the palatal mesenchyme disrupts oral-nasal patterning of the neural crest cell–derived ectomesenchyme of the palatal shelves, leading to defective palatine bone formation and fully penetrant cleft palate. We show that a series of Fox transcription factors, including the novel direct target Foxl1, function downstream of Hh signaling in the secondary palate. Furthermore, we demonstrate that Wnt/bone morphogenetic protein (BMP) antagonists, in particular Sostdc1, are positively regulated by Hh signaling, concomitant with downregulation of key regulators of osteogenesis and BMP signaling effectors. Our data demonstrate that ectopic Hh-Smo signaling downregulates Wnt/BMP pathways, at least in part by upregulating Sostdc1, resulting in cleft palate and defective osteogenesis.

scholarly journals HBO Promotes the Differentiation of Neural Stem Cells via Interactions Between the Wnt3/β-Catenin and BMP2 Signaling Pathways

2019 ◽  
Vol 28 (12) ◽  
pp. 1686-1699 ◽  
Author(s):  
Chongfeng Chen ◽  
Yujia Yang ◽  
Yue Yao
Keyword(s):  
Stem Cells ◽  
Neural Stem Cells ◽  
Signaling Pathways ◽  
System Development ◽  
Nervous System Development ◽  
Bmp Signaling ◽  
Nuclear Proteins ◽  
Therapeutic Effects ◽  
Morphogenetic Protein

Hyperbaric oxygen (HBO) therapy may promote neurological recovery from hypoxic-ischemic encephalopathy (HIE). However, the therapeutic effects of HBO and its associated mechanisms remain unknown. The canonical Wnt/β-catenin signaling pathways and bone morphogenetic protein (BMP) play important roles in mammalian nervous system development. The present study examined whether HBO stimulates the differentiation of neural stem cells (NSCs) and its effect on Wnt3/β-catenin and BMP2 signaling pathways. We showed HBO treatment (2 ATA, 60 min) promoted differentiation of NSCs into neurons and oligodendrocytes in vitro. In addition, rat hypoxic-ischemic brain damage (HIBD) tissue extracts also promoted the differentiation of NSCs into neurons and oligodendrocytes, with the advantage of reducing the number of astrocytes. These effects were most pronounced when these two were combined together. In addition, the expression of Wnt3a, BMP2, and β-catenin nuclear proteins were increased after HBO treatment. However, blockade of Wnt/β-catenin or BMP signaling inhibited NSC differentiation and reduced the expression of Wnt3a, BMP2, and β-catenin nuclear proteins. In conclusion, HBO promotes differentiation of NSCs into neurons and oligodendrocytes and reduced the number of astrocytes in vitro possibly through regulation of Wnt3/β-catenin and BMP2 signaling pathways. HBO may serve as a potential therapeutic strategy for treating HIE.

scholarly journals Effects of Shh and Noggin on neural crest formation demonstrate that BMP is required in the neural tube but not ectoderm

Development ◽  
1998 ◽  
Vol 125 (24) ◽  
pp. 4919-4930 ◽  
Author(s):  
M.A. Selleck ◽  
M.I. Garcia-Castro ◽  
K.B. Artinger ◽  
M. Bronner-Fraser
Keyword(s):  
Neural Crest ◽  
Sonic Hedgehog ◽  
Neural Tube ◽  
Neural Crest Cells ◽  
Neural Plate ◽  
Bmp Signaling ◽  
Neural Tube Closure ◽  
Dorsal Neural Tube ◽  
Neural Ectoderm ◽  
Tube Closure

To define the timing of neural crest formation, we challenged the fate of presumptive neural crest cells by grafting notochords, Sonic Hedgehog- (Shh) or Noggin-secreting cells at different stages of neurulation in chick embryos. Notochords or Shh-secreting cells are able to prevent neural crest formation at open neural plate levels, as assayed by DiI-labeling and expression of the transcription factor, Slug, suggesting that neural crest cells are not committed to their fate at this time. In contrast, the BMP signaling antagonist, Noggin, does not repress neural crest formation at the open neural plate stage, but does so if injected into the lumen of the closing neural tube. The period of Noggin sensitivity corresponds to the time when BMPs are expressed in the dorsal neural tube but are down-regulated in the non-neural ectoderm. To confirm the timing of neural crest formation, Shh or Noggin were added to neural folds at defined times in culture. Shh inhibits neural crest production at early stages (0-5 hours in culture), whereas Noggin exerts an effect on neural crest production only later (5-10 hours in culture). Our results suggest three phases of neurulation that relate to neural crest formation: (1) an initial BMP-independent phase that can be prevented by Shh-mediated signals from the notochord; (2) an intermediate BMP-dependent phase around the time of neural tube closure, when BMP-4 is expressed in the dorsal neural tube; and (3) a later pre-migratory phase which is refractory to exogenous Shh and Noggin.

scholarly journals Reovirus Activates Transforming Growth Factor β and Bone Morphogenetic Protein Signaling Pathways in the Central Nervous System That Contribute to Neuronal Survival following Infection

2009 ◽  
Vol 83 (10) ◽  
pp. 5035-5045 ◽  
Author(s):  
J. David Beckham ◽  
Kathryn Tuttle ◽  
Kenneth L. Tyler
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Signaling Pathways ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Bmp Signaling ◽  
Downstream Signaling ◽  
Morphogenetic Protein ◽  
The Central Nervous System

ABSTRACT Viral infections of the central nervous system (CNS) are important causes of worldwide morbidity and mortality, and understanding how viruses perturb host cell signaling pathways will facilitate identification of novel antiviral therapies. We now show that reovirus infection activates transforming growth factor β (TGF-β) and bone morphogenetic protein (BMP) signaling in a murine model of encephalitis in vivo. TGF-β receptor I (TGF-βRI) expression is increased and its downstream signaling factor, SMAD3, is activated in the brains of reovirus-infected mice. TGF-β signaling is neuroprotective, as inhibition with a TGF-βRI inhibitor increases death of infected neurons. Similarly, BMP receptor I expression is increased and its downstream signaling factor, SMAD1, is activated in reovirus-infected neurons in the brains of infected mice in vivo. Activated SMAD1 and SMAD3 were both detected in regions of brain infected by reovirus, but activated SMAD1 was found predominantly in uninfected neurons in close proximity to infected neurons. Treatment of reovirus-infected primary mouse cortical neurons with a BMP agonist reduced apoptosis. These data provide the first evidence for the activation of TGF-β and BMP signaling pathways following neurotropic viral infection and suggest that these signaling pathways normally function as part of the host's protective innate immune response against CNS viral infection.

scholarly journals Synergistic interaction between the fibroblast growth factor and bone morphogenetic protein signaling pathways in lens cells

2015 ◽  
Vol 26 (13) ◽  
pp. 2561-2572 ◽  
Author(s):  
Bruce A. Boswell ◽  
Linda S. Musil
Keyword(s):  
Gene Expression ◽  
Signaling Pathways ◽  
Bone Morphogenetic Protein ◽  
Primary Cultures ◽  
Bmp Signaling ◽  
Fibroblast Growth ◽  
Lens Development ◽  
Morphogenetic Protein ◽  
Lens Cells ◽  
And Function

Fibroblast growth factors (FGFs) play a central role in two processes essential for lens transparency—fiber cell differentiation and gap junction–mediated intercellular communication (GJIC). Using serum-free primary cultures of chick lens epithelial cells (DCDMLs), we investigated how the FGF and bone morphogenetic protein (BMP) signaling pathways positively cooperate to regulate lens development and function. We found that culturing DCDMLs for 6 d with the BMP blocker noggin inhibits the canonical FGF-to-ERK pathway upstream of FRS2 activation and also prevents FGF from stimulating FRS2- and ERK-independent gene expression, indicating that BMP signaling is required at the level of FGF receptors. Other experiments revealed a second type of BMP/FGF interaction by which FGF promotes expression of BMP target genes as well as of BMP4. Together these studies reveal a novel mode of cooperation between the FGF and BMP pathways in which BMP keeps lens cells in an optimally FGF-responsive state and, reciprocally, FGF enhances BMP-mediated gene expression. This interaction provides a mechanistic explanation for why disruption of either FGF or BMP signaling in the lens leads to defects in lens development and function.

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