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A diagrammatic view of the developing neural tube of a typical vertebrate embryo at the stage when neural ectoderm (NE, stippled) has folded to form open neural folds. Brain and spinal cord develop from the neural tube. Neural crest cells (NC, black) are found at the dorsal edge of the neural folds between the NE and the epidermal ectoderm (EE), from which the skin arises.
Context in source publication
Context 1
... after fertilization, often only after inductive interactions between future ectoderm and endoderm (Hall 1998a(Hall , 1998b(Hall , 1999). The neural crest, which is the dorsalmost portion of the neural folds in all vertebrate embryos, also arises secondarily, following inductive interactions between two types of ectoderm-neural and epidermal (Fig. 1). Both mesoderm and neural crest break up into populations of cells that migrate away from the midline to form a diversity of cell types (Hall ...
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The neural crest cell (NCC) lineage is often referred to as the fourth germ layer in embryos, as its wide range of migration and early colonization of multiple tissues and organ systems throughout the developing body is astounding. Many human birth defects are thought to have their origins within the NCC lineage. Exciting recent conditional mouse t...
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Citations
... Although NCCs are an ectodermal derivative, they can be differentiated into mesodermal or endodermal tissues due to EMT [5] and are thus considered the fourth germ layer. [6] Multiple tissues originate from NCCs and are causative factors in many head and neck pathologies. In the present study, we briefly describe the NC derivatives and 17 cases of this rare group of entities (cephalic NC diseases) who presented to our department in the past 3 years. ...
Objectives
Neural crest cells (NCCs) are transient structures in the fetal life in vertebrates, which develop at the junctional site of the non-neural and neural ectoderm, sharing a common developmental origin for diverse diseases. After Epithelio-mesenchymal (EMT) of the NCCs within the neural tube, delamination of NCCs occurs. After delamination, the transformation of these cells into various cell lineages produces melanocytes, bones, and cartilage of the skull, cells of the enteric and peripheral nervous system. After the conversion, these cells migrate into various locations of the entire body according to the cell lineage. Abnormalities in neural crest (NC) formation and migration result in various malformations and tumors, known as neurocristopathy.
Material and Methods
Herein, this case series describes a single-center experience in cephalic NC disorders over the past 3 years, including 17 cases of varying composition (i.e., vascular, dysgenetic, mixed, and neoplastic forms) involving the brain and occasionally skin, eyes, and face of the patients.
Results
In our study of 17 patients with cephalic NC disease, 6 (35.3%) patients had vascular form, 5 (29.4%) had dysgenetic form, 4 (23.5%) had mixed form, and 2 (11.7%) had neoplastic form. Brain involvement in the form of vascular or parenchyma or both vascular and parenchymal was seen in all of our patients (100%), skin in 6 (35.3%) patients, eye in 2 (11.7%), and face in 1 (5.9%) patient. Treatment was planned according to the various manifestations of the disease.
Conclusion
Neural crest diseases (NCDs) are a rare and under-recognized group of disorders in the literature and may have been under-reported due to a lack of awareness regarding the same. More such reporting may increase the repertoire of these rare disorders such that clinicians can have a high degree of suspicion leading to early detection and timely counseling and also improve preventive strategies and help in developing new drugs for these disorders or prevent them.
... Although NCCs are an ectodermal derivative, they can be differentiated into mesodermal or endodermal tissues due to EMT [5] and are thus considered the fourth germ layer. [6] Multiple tissues originate from NCCs and are causative factors in many head and neck pathologies. In the present study, we briefly describe the NC derivatives and 17 cases of this rare group of entities (cephalic NC diseases) who presented to our department in the past 3 years. ...
... Among the invading cells, neural crest cells are unique in their ability to differentiate into diverse cell types, an ability that has resulted in neural crest cells being described as the fourth germ layer (Hall 2000). Neural crest cells are migratory and multipotent cells known to generate diverse cell types in a number of developing tissues (see Le Douarin et al. (2004), andZhang et al. (2014) for further details). ...
The pituitary gland is a major endocrine tissue composing of two distinct entities, the adenohypophysis (anterior pituitary, cranial placode origin) and the neurohypophysis (posterior pituitary, neural ectoderm origin), and plays important roles in maintaining vital homeostasis. This tissue is maintained by a slow, consistent cell-renewal system of adult stem/progenitor cells. Recent accumulating evidence shows that neural crest-, head mesenchyme-, and endoderm lineage cells invade during pituitary development and contribute to the maintenance of the adult pituitary gland. Based on these novel observations, this article discusses whether these lineage cells are involved in pituitary organogenesis, maintenance, regeneration, dysplasia, or tumors.
... An interplay of locally produced growth factors probably regulates local bone formation in salmon. Because the skeletogenic cells that generate the jaws are neural crestderived, and considering that skeletogenic cells of the kype develop into osteoblasts and chondroblasts (Hall, 2000;Witten & Hall, 2002), additional factors such as N-CAM (neural cell adhesion molecule) are probably involved in differentiation of the kype skeleton. N-CAM regulates the development of membrane bone scleroblasts into osteoblast and down-regulation of N-CAM is required for chondrogenic differentiation (Fang & Hall, 1997, 1999. ...
Vertebral bodies are composed of two types of metameric elements, centra and arches, each of which is considered as a developmental module. Most parts of the teleost vertebral column have a one-to-one relationship between centra and arches, although, in all teleosts, this one-to-one relationship is lost in the caudal fin endoskeleton. Deviation from the one-to-one relationship occurs in most vertebrates, related to changes in the number of vertebral centra or to a change in the number of arches. In zebrafish, deviations also occur predominantly in the caudal region of the vertebral column. In-depth phenotypic analysis of wild-type zebrafish was performed using whole-mount stained samples, histological analyses and synchrotron radiation X-ray tomographic microscopy 3D reconstructions. Three deviant centra phenotypes were observed: (i) fusion of two vertebral centra, (ii) wedge-shaped hemivertebrae and (iii) centra with reduced length. Neural and haemal arches and their spines displayed bilateral and unilateral variations that resemble vertebral column phenotypes of stem-ward actinopterygians or other gnathostomes as well as pathological conditions in extant species. Whether it is possible to distinguish variations from pathological alterations and whether alterations resemble ancestral conditions is discussed in the context of centra and arch variations in other vertebrate groups and basal actinopterygian species.
... During evolution, the transition from protochordates to vertebrates was marked by the appearance of a new structure, the NC. Absent in protochordates, the NC is a vertebrate innovation, a synapomorphic character unique to this group: given the diversity of lineages it generates, the NC can be considered as a fourth germ layer, making vertebrates quadroblastic organisms [90][91][92]. ...
... Anterior to the pineal anlage, the neural fold does not produce migrating CNC [90,93,94], but gives rise to the pituitary anlage medially ( Figure 3A-C), which is contiguous with the rostral end of the notochord in early neurula. From the mesio-lateral territories of the neural fold, the nasal mucosa, the olfactory placodes, as well as the ectoderm destined to cover the naso-frontal bud and the phyltrum region develop. ...
The neural crest, a unique cell population originating from the primitive neural field, has a multi-systemic and structural contribution to vertebrate development. At the cephalic level, the neural crest generates most of the skeletal tissues encasing the developing forebrain and provides the prosencephalon with functional vasculature and meninges. Over the last decade, we have demonstrated that the cephalic neural crest (CNC) exerts an autonomous and prominent control on the development of the forebrain and sense organs. The present paper reviews the primary mechanisms by which CNC can orchestrate vertebrate encephalization. Demonstrating the role of the CNC as an exogenous source of patterning for the forebrain provides a novel conceptual framework with profound implications for understanding neurodevelopment. From a biomedical standpoint, these data suggest that the spectrum of neurocristopathies is broader than expected and that some neurological disorders may stem from CNC dysfunctions.
... Vertebrate NCCs are a pluripotent lineage of early embryonic cells, which initially line the two crests of the neural fold, fusing them to create the neural tube, then dispersing throughout the developing embryo to form numerous other types of cells, tissues, structures and organs [2][3][4]. They are a defining feature of vertebrate evolution, and have been described as 'a fourth germ layer' in vertebrate development [3]. ...
... Vertebrate NCCs are a pluripotent lineage of early embryonic cells, which initially line the two crests of the neural fold, fusing them to create the neural tube, then dispersing throughout the developing embryo to form numerous other types of cells, tissues, structures and organs [2][3][4]. They are a defining feature of vertebrate evolution, and have been described as 'a fourth germ layer' in vertebrate development [3]. Wilkins et al. [1,5] suggest that ancient selection for tame behaviour-like that applied in the Russian fox experiment-caused heritable reductions in aggression by disrupting documented NCC contributions to the vertebrate endocrine and autonomic nervous systems [11,63]; especially via the pituitary, adrenal medulla, and related ganglia. ...
Altered neural crest cell (NCC) behaviour is an increasingly cited explanation for the domestication syndrome in animals. However, recent authors have questioned this explanation, while others cast doubt on whether domestication syndrome even exists. Here, we review published literature concerning this syndrome and the NCC hypothesis, together with recent critiques of both. We synthesize these contributions and propose a novel interpretation, arguing shared trait changes under ancient domestication resulted primarily from shared disruption of wild reproductive regimes. We detail four primary selective pathways for 'reproductive disruption' under domestication and contrast these succinct and demonstrable mechanisms with cryptic genetic associations posited by the NCC hypothesis. In support of our perspective, we illustrate numerous important ways in which NCCs contribute to vertebrate reproductive phenotypes, and argue it is not surprising that features derived from these cells would be coincidentally altered under major selective regime changes, as occur in domestication. We then illustrate several pertinent examples of Darwin's 'unconscious selection' in action, and compare applied selection and phenotypic responses in each case. Lastly, we explore the ramifications of reproductive disruption for wider evolutionary discourse, including links to wild 'self-domestication' and 'island effect', and discuss outstanding questions.
... During evolution, the transition from protochordates to vertebrates was marked by the appearance of a new structure, the NC. Absent in protochordates, the NC is a vertebrate innovation, a synapomorphic character unique to this group : given the diversity of lineages it generates, the NC can be considered as a fourth germ layer, making vertebrates quadroblastic organisms [89][90][91]. ...
The neural crest, a unique cell population originating from the primitive neural field, has a multi-systemic and structural contribution to vertebrate development. At the cephalic level, the neural crest generates most of the skeletal tissues encasing the developing forebrain and provides the prosencephalon with functional vasculature and meninges. Over the last decade, we have demonstrated that the cephalic neural crest (CNC) exerts an autonomous and prominent control on forebrain and sense organs development. The present paper reviews the primary mechanisms by which CNC can orchestrate vertebrate encephalization. Demonstrating the role of the CNC as an exogenous source of patterning for the forebrain provides a novel conceptual framework with profound implications for understanding neurodevelopment. From a biomedical standpoint, these data suggest that the spectrum of neurocristopathies is broader than expected and that some neurological disorders may stem from CNC dysfunctions.
... Neural crest cells (NCCs) are often touted as the "fourth germ layer" [1] for the range of derivative cell types they produce, and many species-defining characteristics like facial shape and coloration are generated from this embryonic lineage. The influence of these cells in human health has been long recognized, with a broad spectrum of conditions classified as neurocristopathies [2] because of their shared developmental origin in NCCs. ...
Vertebrates have some of the most complex and diverse features in animals, from varied craniofacial morphologies to colorful pigmentation patterns and elaborate social behaviors. All of these traits have their developmental origins in a multipotent embryonic lineage of neural crest cells. This “fourth germ layer” is a vertebrate innovation and the source of a wide range of adult cell types. While others have discussed the role of neural crest cells in human disease and animal domestication, less is known about their role in contributing to adaptive changes in wild populations. Here, we review how variation in the development of neural crest cells and their derivatives generates considerable phenotypic diversity in nature. We focus on the broad span of traits under natural and sexual selection whose variation may originate in the neural crest, with emphasis on behavioral factors such as intraspecies communication that are often overlooked. In all, we encourage the integration of evolutionary ecology with developmental biology and molecular genetics to gain a more complete understanding of the role of this single cell type in trait covariation, evolutionary trajectories, and vertebrate diversity.
... It is induced at the neural plate border (NB) by a multistep signalling process involving BMP, Wnt, FGF as well as Notch and RA signals emerging from the NP, epidermis and lateral mesoderm (Basch et al., 2004;Steventon et al., 2005;Sauka-Spengler & Bronner-Fraser, 2008). NCCs contribute to various cell types and tissues in the adult organism and are therefore often referred to as the fourth germ layer (Hall, 2000). ...
Despite the abundant variability among adult vertebrate body plans, the developmental steps transforming the single zygote into a multicellular organism of remarkable complexity, are evolutionary highly conserved. Morphogenetic processes such as gastrulation, neural tube closure, body axis extension, neural crest cell migration and organogenesis are thereby at the heart of embryogenesis. Especially the formation of a closed neural tube, which gives rise to the central nervous system, constitutes a fundamental event. Neural tube closure is achieved by convergent extension movements and by apical constriction of neuroepithelial cells. Along with proceeding neurulation, cranial neural cells start to delaminate from the neuroepithelial border. In order to initiate directed migration movements, neural crest cells require polarised cell protrusions and mediate mechanical forces. Changes in cell shape and motility underlying neural tube closure and neural crest cell migration are controlled by specific regulation of the actin cytoskeleton. How these actin dynamics and the myosin-mediated contraction of actin networks are precisely coordinated is not fully understood. In this context, actin filament-associated proteins play an important role for the structural organisation of different actin network types. Calponins constitute an evolutionary highly conserved family of F-actin binding proteins, which are able to influence actin-myosin dynamics and to stabilise actin filaments. Previous studies already demonstrated a role of Calponin proteins in smooth muscle contraction, cell motility and phagocytosis. Vertebrates possess three Calponin isoforms, each displaying specific expression patterns and functions. Calponin2 is expressed in a variety of cell types and several studies performed in vitro indicated that Calponin2 is important for mechanical tension mediation during the course of cell migration. In the early embryo of Xenopus laevis, calponin2 is expressed in tissues that undergo extensive morphogenetic movements and cell migration. This implies an elemental role of Calponin2 for respective morphogenetic steps during embryonic development of this well-established model organism. Within the scope of the present work, the specific function of Calponin2 for dynamic regulation of the actin cytoskeleton was analysed more closely. Localisation of the protein, by utilising a tagged construct, was shown in neural plate cells as well as in migrating neural crest cells. In both cell types, regulated protein degradation occurred, which led to specific expression restricted to the apex of constricting neural plate cells or to forming lamellipodia. Thus, tagged Calponin2 localised to regions of the actin cortex. Loss of Calponin2 function led to defects in neural crest cell specification and migration as well as in convergent extension and apical constriction within the neural plate. All induced phenotypes were rescued by additional calponin2 mRNA injection. In summary, these data demonstrated a specific function of Calponin2 for correct formation of the neural crest as well as for neural tube closure. Furthermore, the precise regulation of protein expression levels, which directly correlated with correct Calponin2 function, was dependent on specific domains that potentially mediate actin-binding. Clik1, Clik2 and the C-terminus were identified as a critical unit regulating protein degradation, both in neural crest cells and neural plate cells. Additionally, it was shown that Calponin2 function for neural apical constriction depends on each of these domains as well. Overall, the degradation of Calponin2, regulated via its F-actin binding, implies a filament stabilising function. Thus, a temporospatial coordination of protein degradation would be necessary to enable dynamic changes of the actin cytoskeleton by a regulated release of actin filaments and to allow the association of other structural effectors during morphogenetic processes of early vertebrate development.
... A VS-sejtek sokirányú elkülönülésének ez a képessége ellentmond a "csíraréteg szabály"-nak, amely a három primér csíraréteg állandó kizárólagosságát jelenti (38). Az embryonális fejlődés alatt a VS-sejtek késői megjelenése, ezeknek a sejteknek a sok irányú differenciálódási lehetőségei és e sejt származékoknak a szervezet szövetein át történő diffúz áthatoló képessége miatt a velősáncot a "negyedik csíraréteg"-nek lehet tekinteni az ektoderma, mesoderma és endoderma primér csírarétegek mellett (39). ...
In the course of their migration the neural crest cells reach all parts of the developing embryo. The frst wave of the derivatives of these cells the melanoblasts and melanocytes harbour in the epidermis and hair follicles during the dorsolateral migration. A number of signal molecules and proteases play an important role in the course of melanocyte migration through the extracellular matrix. The Mongolian spots appear as a consequence of the transient inhibition of melanocyte migration and in the case of fnal obstruction the Ota-, or. Ito nevuses. The Blaschko lines based on cutaneous mosaicism are of great diagnostic importance and on the ground of these lines the blaschkitises can appear under the exogenous factors. The blaschkolinear acquired infammatory skin eruption (BLAISE) is an acquired infammatory process. One of its variants is the lichen striatus and the other is the blaschkitis. The blaschkolinear dermatoses can appear usually as a nevoid disease. The pathological development of the neural crest cells can induce pathological processes in other tissues of the body as well, which may appear in the form of the so-called neurocristopathies including approximately ffty manifestations. The knowledge of the diferent pigmentation forms as well as the pathological symptoms of neurocristopathies is of great importance for the clinican from a diagnostic point of view.
