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Annual Review of Genetics 2014The formation of the embryonic brain and spinal cord begins as the neural plate bends to form the neural folds, which meet and adhere to close the neural tube. The... (Review)
Review
The formation of the embryonic brain and spinal cord begins as the neural plate bends to form the neural folds, which meet and adhere to close the neural tube. The neural ectoderm and surrounding tissues also coordinate proliferation, differentiation, and patterning. This highly orchestrated process is susceptible to disruption, leading to neural tube defects (NTDs), a common birth defect. Here, we highlight genetic and epigenetic contributions to neural tube closure. We describe an online database we created as a resource for researchers, geneticists, and clinicians. Neural tube closure is sensitive to environmental influences, and we discuss disruptive causes, preventative measures, and possible mechanisms. New technologies will move beyond candidate genes in small cohort studies toward unbiased discoveries in sporadic NTD cases. This will uncover the genetic complexity of NTDs and critical gene-gene interactions. Animal models can reveal the causative nature of genetic variants, the genetic interrelationships, and the mechanisms underlying environmental influences.
Topics: Animals; Brain; Epigenesis, Genetic; Female; Neural Crest; Neural Plate; Neural Tube; Spinal Cord
PubMed: 25292356
DOI: 10.1146/annurev-genet-120213-092208 -
Proceedings of the National Academy of... May 2022Neurulation is the process in early vertebrate embryonic development during which the neural plate folds to form the neural tube. Spinal neural tube folding in the...
Neurulation is the process in early vertebrate embryonic development during which the neural plate folds to form the neural tube. Spinal neural tube folding in the posterior neuropore changes over time, first showing a median hinge point, then both the median hinge point and dorsolateral hinge points, followed by dorsolateral hinge points only. The biomechanical mechanism of hinge point formation in the mammalian neural tube is poorly understood. Here we employ a mechanical finite element model to study neural tube formation. The computational model mimics the mammalian neural tube using microscopy data from mouse and human embryos. While intrinsic curvature at the neural plate midline has been hypothesized to drive neural tube folding, intrinsic curvature was not sufficient for tube closure in our simulations. We achieved neural tube closure with an alternative model combining mesoderm expansion, nonneural ectoderm expansion, and neural plate adhesion to the notochord. Dorsolateral hinge points emerged in simulations with low mesoderm expansion and zippering. We propose that zippering provides the biomechanical force for dorsolateral hinge point formation in settings where the neural plate lateral sides extend above the mesoderm. Together, these results provide a perspective on the biomechanical and molecular mechanism of mammalian spinal neurulation.
Topics: Animals; Ectoderm; Humans; Mice; Neural Plate; Neural Tube; Neurulation; Notochord
PubMed: 35561223
DOI: 10.1073/pnas.2117075119 -
Frontiers in Physiology 2020The 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... (Review)
Review
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.
PubMed: 33364980
DOI: 10.3389/fphys.2020.608880 -
Current Topics in Developmental Biology 2015Cranial sensory placodes derive from discrete patches of the head ectoderm and give rise to numerous sensory structures. During gastrulation, a specialized "neural... (Review)
Review
Cranial sensory placodes derive from discrete patches of the head ectoderm and give rise to numerous sensory structures. During gastrulation, a specialized "neural border zone" forms around the neural plate in response to interactions between the neural and nonneural ectoderm and signals from adjacent mesodermal and/or endodermal tissues. This zone subsequently gives rise to two distinct precursor populations of the peripheral nervous system: the neural crest and the preplacodal ectoderm (PPE). The PPE is a common field from which all cranial sensory placodes arise (adenohypophyseal, olfactory, lens, trigeminal, epibranchial, otic). Members of the Six family of transcription factors are major regulators of PPE specification, in partnership with cofactor proteins such as Eya. Six gene activity also maintains tissue boundaries between the PPE, neural crest, and epidermis by repressing genes that specify the fates of those adjacent ectodermally derived domains. As the embryo acquires anterior-posterior identity, the PPE becomes transcriptionally regionalized, and it subsequently becomes subdivided into specific placodes with distinct developmental fates in response to signaling from adjacent tissues. Each placode is characterized by a unique transcriptional program that leads to the differentiation of highly specialized cells, such as neurosecretory cells, sensory receptor cells, chemosensory neurons, peripheral glia, and supporting cells. In this review, we summarize the transcriptional and signaling factors that regulate key steps of placode development, influence subsequent sensory neuron specification, and discuss what is known about mutations in some of the essential PPE genes that underlie human congenital syndromes.
Topics: Afferent Pathways; Ectoderm; Gene Expression Regulation, Developmental; Head; Humans; Models, Biological; Neural Plate; Signal Transduction
PubMed: 25662264
DOI: 10.1016/bs.ctdb.2014.11.009 -
Developmental Biology May 2014The neural crest and craniofacial placodes are two distinct progenitor populations that arise at the border of the vertebrate neural plate. This border region develops... (Review)
Review
The neural crest and craniofacial placodes are two distinct progenitor populations that arise at the border of the vertebrate neural plate. This border region develops through a series of inductive interactions that begins before gastrulation and progressively divide embryonic ectoderm into neural and non-neural regions, followed by the emergence of neural crest and placodal progenitors. In this review, we describe how a limited repertoire of inductive signals-principally FGFs, Wnts and BMPs-set up domains of transcription factors in the border region which establish these progenitor territories by both cross-inhibitory and cross-autoregulatory interactions. The gradual assembly of different cohorts of transcription factors that results from these interactions is one mechanism to provide the competence to respond to inductive signals in different ways, ultimately generating the neural crest and cranial placodes.
Topics: Animals; Body Patterning; Bone Morphogenetic Proteins; Ectoderm; Epidermal Growth Factor; Gene Expression Regulation, Developmental; Humans; Neural Crest; Neural Plate; Wnt Proteins
PubMed: 24321819
DOI: 10.1016/j.ydbio.2013.11.027 -
Frontiers in Cell and Developmental... 2022Pax3/7 factors play numerous roles in the development of the dorsal nervous system of vertebrates. From specifying neural crest at the neural plate borders, to...
Pax3/7 factors play numerous roles in the development of the dorsal nervous system of vertebrates. From specifying neural crest at the neural plate borders, to regulating neural tube closure and patterning of the resulting neural tube. However, it is unclear which of these roles are conserved in non-vertebrate chordates. Here we investigate the expression and function of Pax3/7 in the model tunicate Pax3/7 is expressed in neural plate border cells during neurulation, and in central nervous system progenitors shortly after neural tube closure. We find that separate regulatory elements control the expression in these two distinct lineages. Using CRISPR/Cas9-mediated mutagenesis, we knocked out in F0 embryos specifically in these two separate territories. knockout in the neural plate borders resulted in neural tube closure defects, suggesting an ancient role for Pax3/7 in this chordate-specific process. Furthermore, knocking out in the neural impaired Motor Ganglion neuron specification, confirming a conserved role for this gene in patterning the neural tube as well. Taken together, these results suggests that key functions of Pax3/7 in neural tube development are evolutionarily ancient, dating back at least to the last common ancestor of vertebrates and tunicates.
PubMed: 36172287
DOI: 10.3389/fcell.2022.999511 -
Developmental Dynamics : An Official... Aug 2020A common theme in organogenesis is how the final structure of organs emerge from epithelial tube structures, with the formation of the neural tube being one of the best... (Review)
Review
A common theme in organogenesis is how the final structure of organs emerge from epithelial tube structures, with the formation of the neural tube being one of the best examples. Two types of cell movements co-occur during neural tube closure involving the migration of cells toward the midline of the embryo (mediolateral intercalation or convergent extension) as well as the deep movement of cells from inside the embryo to the outside of the lateral side of the neural plate (radial intercalation). Failure of either type of cell movement will prevent neural tube closure, which can produce a range of neural tube defects (NTDs), a common congenital disease in humans. Numerous studies have identified signaling pathways that regulate mediolateral intercalation during neural tube closure. Less understood are the pathways that govern radial intercalation. Using the Xenopus laevis system, our group reported the identification of transient receptor potential (TRP) channels, TRPM6 and TRPM7, and the Mg ion they conduct, as novel and key factors regulating both mediolateral and radial intercalation during neural tube closure. Here we broadly discuss tubulogenesis and cell intercalation from the perspective of neural tube closure and the respective roles of TRPM7 and TRPM6 in this critical embryonic process.
Topics: 3T3 Cells; Animals; Cell Movement; Embryonic Development; Gene Expression Regulation, Developmental; Humans; Ions; Magnesium; Mice; Neural Plate; Neural Tube; Neural Tube Defects; Neurulation; Protein Domains; Protein Serine-Threonine Kinases; Signal Transduction; TRPM Cation Channels; Xenopus Proteins; Xenopus laevis; Zebrafish
PubMed: 32315468
DOI: 10.1002/dvdy.182 -
Communications Biology Jan 2021Primary neurulation is the process by which the neural tube, the central nervous system precursor, is formed from the neural plate. Incomplete neural tube closure occurs...
Primary neurulation is the process by which the neural tube, the central nervous system precursor, is formed from the neural plate. Incomplete neural tube closure occurs frequently, yet underlying causes remain poorly understood. Developmental studies in amniotes and amphibians have identified hingepoint and neural fold formation as key morphogenetic events and hallmarks of primary neurulation, the disruption of which causes neural tube defects. In contrast, the mode of neurulation in teleosts has remained highly debated. Teleosts are thought to have evolved a unique mode of neurulation, whereby the neural plate infolds in absence of hingepoints and neural folds, at least in the hindbrain/trunk where it has been studied. Using high-resolution imaging and time-lapse microscopy, we show here the presence of these morphological landmarks in the zebrafish anterior neural plate. These results reveal similarities between neurulation in teleosts and other vertebrates and hence the suitability of zebrafish to understand human neurulation.
Topics: Animals; Animals, Genetically Modified; Cell Movement; Cell Shape; Epithelial Cells; Homeodomain Proteins; Luminescent Proteins; Morphogenesis; Neural Plate; Neural Tube; Neural Tube Defects; Neurulation; Prosencephalon; Recombinant Fusion Proteins; Time Factors; Time-Lapse Imaging; Transcription Factors; Zebrafish
PubMed: 33514864
DOI: 10.1038/s42003-021-01655-8 -
Developmental Biology Dec 2017The formation of the spinal cord during early embryonic development in vertebrate embryos is a continuous process that begins at gastrulation and continues through to... (Review)
Review
The formation of the spinal cord during early embryonic development in vertebrate embryos is a continuous process that begins at gastrulation and continues through to the completion of somitogenesis. Despite the conserved usage of patterning mechanisms and gene regulatory networks that act to generate specific spinal cord progenitors, there now exists two seemingly disparate models to account for their action. In the first, a posteriorly localized signalling source transforms previously anterior-specified neural plate into the spinal cord. In the second, a population of bipotent stem cells undergo continuous self-renewal and differentiation to progressively lay down the spinal cord and axial mesoderm by posterior growth. Whether this represents fundamental differences between the experimental model organisms utilised in the generation of these models remains to be addressed. Here we review lineage studies across four key vertebrate models: mouse, chicken, Xenopus and zebrafish and relate them to the underlying gene regulatory networks that are known to be required for spinal cord formation. We propose that by applying a dynamical systems approach to understanding how distinct neural and mesodermal fates arise from a bipotent progenitor pool, it is possible to begin to understand how differences in the dynamical cell behaviours such as proliferation rates and cell movements can map onto conserved regulatory networks to generate diversity in the timing of tissue generation and patterning during development.
Topics: Animals; Cell Differentiation; Chickens; Developmental Biology; Mesoderm; Mice; Models, Animal; Morphogenesis; Neural Plate; Spinal Cord; Stem Cells; Xenopus; Zebrafish
PubMed: 28192080
DOI: 10.1016/j.ydbio.2017.01.021 -
Wiley Interdisciplinary Reviews.... Jul 2013In vertebrates, the development of the nervous system is triggered by signals from a powerful 'organizing' region of the early embryo during gastrulation. This... (Review)
Review
In vertebrates, the development of the nervous system is triggered by signals from a powerful 'organizing' region of the early embryo during gastrulation. This phenomenon--neural induction--was originally discovered and given conceptual definition by experimental embryologists working with amphibian embryos. Work on the molecular circuitry underlying neural induction, also in the same model system, demonstrated that elimination of ongoing transforming growth factor-β (TGFβ) signaling in the ectoderm is the hallmark of anterior neural-fate acquisition. This observation is the basis of the 'default' model of neural induction. Endogenous neural inducers are secreted proteins that act to inhibit TGFβ ligands in the dorsal ectoderm. In the ventral ectoderm, where the signaling ligands escape the inhibitors, a non-neural fate is induced. Inhibition of the TGFβ pathway has now been demonstrated to be sufficient to directly induce neural fate in mammalian embryos as well as pluripotent mouse and human embryonic stem cells. Hence the molecular process that delineates neural from non-neural ectoderm is conserved across a broad range of organisms in the evolutionary tree. The availability of embryonic stem cells from mouse, primates, and humans will facilitate further understanding of the role of signaling pathways and their downstream mediators in neural induction in vertebrate embryos.
Topics: Animals; Body Patterning; Embryonic Induction; Genes, Developmental; Humans; Neural Plate; Neural Stem Cells; Neurogenesis; Transforming Growth Factor beta; Vertebrates
PubMed: 24014419
DOI: 10.1002/wdev.90