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At least 19 recordsLinked to original sources

A time-resolved single-cell roadmap of the logic driving anterior neural crest diversification from neural border to migration stages.

Neural crest cells exemplify cellular diversification from a multipotent progenitor population. However, the full sequence of early molecular choices orchestrating the emergence of neural crest heterogeneity from the embryonic ectoderm remains elusive. Gene-regulatory-networks (GRN) govern early development and cell specification toward definitive neural crest. Here, we combine ultradense single-cell transcriptomes with machine-learning and large-scale transcriptomic and epigenomic experimental validation of selected trajectories, to provide the general principles and highlight specific features of the GRN underlying neural crest fate diversification from induction to early migration stages using Xenopus frog embryos as a model. During gastrulation, a transient neural border zone state precedes the choice between neural crest and placodes which includes multiple converging gene programs. During neurulation, transcription factor connectome, and bifurcation analyses demonstrate the early emergence of neural crest fates at the neural plate stage, alongside an unbiased multipotent-like lineage persisting until epithelial-mesenchymal transition stage. We also decipher circuits driving cranial and vagal neural crest formation and provide a broadly applicable high-throughput validation strategy for investigating single-cell transcriptomes in vertebrate GRNs in development, evolution, and disease.

Animals

Hox/Meis-dependent gene-regulatory transition underlies cardiopharyngeal neural crest diversification.

Neural crest cells (NCCs) are multipotent migratory cells essential for cardiac development, yet the lineage trajectories and gene regulatory networks underlying their differentiation in the cardiopharyngeal region remain unclear. Here, we integrate single-cell RNA-seq, spatial transcriptomics, and multiomic analyses to construct a comprehensive map of NCC lineages in developing mouse cardiopharyngeal tissues. We identify a transition from Hox-positive pharyngeal NCCs to Hox-negative intracardiac populations associated with the outflow tract cushion, accompanied by a shift in Meis transcription factor binding and gene-regulatory network architecture. By contrast, NCCs forming the aorticopulmonary septum and great vessel smooth muscle retain distinct Hox-codes. A Meis2-Sox9-Scx gene-regulatory network defines a skeletogenic progenitor-like intermediate state that gives rise to coronary artery smooth muscle and semilunar valves. Our findings suggest that the loss of Hox-dependent regional identity enables pharyngeal NCCs to acquire new fates upon entering the cardiac cushion, providing insight into the developmental origins of coronary and valvular calcification.

Journal Article

Independent expression of the adrenergic phenotype by neural crest cells in vitro.

Neural crest cells obtained from Japanese quail and grown in vitro without other embryonic tissues differentiate into adrenergic cells. These cells show intense catecholamine-specific histochemical fluorescence, and some have long, varicose neuronal processes. Ultrastructural examination shows two populations of cells, one with small (about 90 nm) dense-core vesicles resembling principal sympathetic neurons and the other with larger (about 150 nm) dense-core granules resembling chromaffin or small intensely fluorescent cells. Neuronal cells without adrenergic characteristics are also present. These results are compatible with the hypothesis that a population of cells determined along neuronal lines exists in the neural crest prior to migration.

Animals

Neural crest cells: temperature-dependent transformation by Rous sarcoma virus.

Cranial neural crest cells from chick embryos, when cultured under appropriate conditions, differentiate after approx. 1 week into pigmented cells. Neurol crest cells were infested with a mutant (RSV-BH-Ta) of the Bryan 'high titer' strain of Rous sarcoma virus on the second day of culture before the cells were morphologically differentiated, or later after they became pigmented. Cells infected and maintained at the temperature permissive for transformation (37 degrees C) proliferated rapidly compared to uninfected cells are produced extensive cytoplasmic vacuoles in a fashion similar to other types of cells transformed with RSV-BH-Ta at 37 degrees C. Cells infected and maintained at the non-permissive temperature for transformation (41 degrees C) also proliferated rapidly but did not become morphologically transformed. Transformation occurred reversibly following a shift of temperature. Infection of morphologically undifferentiated neural crest cells at either temperature prevented their differentiation into pigment cells, and infection of pigmented neural crest cells at either temperature led to a gradual loss of pigmentation. These results suggest that even at the non-permissive temperature the virus may regulate the state of differentiation of certain types of cells.

Animals

Anionic glycopeptides and glycosaminoglycans synthesized by embryonic neural tube and neural crest.

Anionic glycopeptides and glycosaminoglycans synthesized by embryonic neural tube (epithelium) and neural crest (mesenchymal outgrowth) developing in vitro were examined. The profile of surface glycopeptides is relatively simple (two major ones for neural crest; four major ones for neural tube). There is one major glycopeptide found in the medium which is present only in trace amounts on the cells. Both hyaluronate and chondroitin sulfate are synthesized. Hyaluronate is predominantly cell associated; chondroitin sulfate is found predominantly in the medium. It is suggested that independent sorting of these relatively few glycopeptides can result in qualitative surface differences. Morphological state (epithelial or mesenchymal) and differentiated state may be related to these differences as well as to quantitative differences in surface glycosaminoglycans.

Animals

Relationships between neural crest cells and catecholamine in suckling mice.

In suckling mice injected i.p. with a 27 mg/kg dose of L-hydrochloric acid isoproterenol, multiple neural crest tumors developed and cell death of neural crest cells occurred. It is speculated that neural crest derivatives may be beta-receptor cells and contain regulatory units of neurotransmission mediated through cyclic AMP.

Animals

Defining active and repressive chromatin states in neural crest cells using low-input CUT&RUN.

The transition of neural crest cells (NCCs) from a multipotent state to lineage-restricted derivatives, including melanocytes, is governed by tightly regulated epigenetic mechanisms that orchestrate cell type specific gene expression programs. Histone post-translational modifications (PTMs), in particular, play an important role in modulating chromatin accessibility, enhancer activation, and transcription factor occupancy, thereby facilitating dynamic chromatin and transcriptional reprogramming required during development. However, profiling such chromatin states in rare and transient Neural Crest Cell (NCC) populations in vivo remains technically challenging. To address this, we present an optimized low-input Cleavage Under Targets and Release Using Nuclease (CUT&RUN) workflow tailored for fluorescence-activated cell sorting (FACS) isolated NCCs from zebrafish embryos. This approach enables high-resolution and low-background mapping of key histone modifications, including H3K27ac, H3K4me3, and H3K27me3, from limited cell numbers. Collectively, these methodologies provide a robust framework for dissecting chromatin state dynamics in developmental systems and can also offer insights into epigenetic dysregulation associated with disease.

Animals

Multiple oncogenesis of neural crest cells by steroids in suckling mice.

In suckling mice injected with steroids, multiple tumors occurred in the sites where neural crest cells normally are present. It is speculated that the phase of the cell cycle of the neural crest cells may have something to do with its cell surface and cellular phenotypic expression in the system mediated by cyclic AMP.

Animals

Migratory patterns of cloned neural crest melanocytes injected into host chicken embryos.

Cloned quail melanocytes grown in tissue culture for 8 days or more were injected into 2 1/2-day-old chicken embryos. The pigment cells were placed directly into the somitic lumen by means of an injection micropipette. This technique for introducing marked neural crest cells into host embryos causes far less damage than previous methods which require extirpation and replacement of the neural tube. In addition, small numbers of homogeneous cells can be implanted by this procedure. When injected into one of the posterior somites, cultured pigment cells migrated along the ventral neural crest pathway. Three days after injection the melanocytes had migrated ventral to the dorsal root ganglia and prevertebral and primary sympathetic chain ganglia and were seen associated with the adrenal gland and aortic plexi. Melanocytes were frequently found in or adjacent to the gonads and often had migrated as far as the gut.

Animals

[Neurocristopathies : embryology, physiology, and pathology of the neural crest derivatives (author's transl)].

The authors review various of the derivatives of the neural crest, consider their relationship with the APUD System, and deduce the physiopathological consequences applicable to these cells, whose only similarity lies in their common embryologic origin. They propose a system of classification of interrelated pathological conditions that these cells may show, an detail clinical information as well as the mode of genetic transmission of the principal neurocristopathic syndroms.

APUD Cells

Neural properties of cultured human endocrine tumor cells of proposed neural crest origin.

Cells from human endocrine tumors of proposed neural crest origin--five pheochromocytomas, two medullary carcinomas of the thyroid, and two bronchial carcinoids--were grown in monolayer culture. Cells from all nine tumors, including epithelial forms of medullary carcinoma of the thyroid and bronchial carcinoid cells, and epithelial and neuron-like pheochromocytoma cells demonstrated all-or-nothing, short-duration action potentials.

Action Potentials

Routine reversed-phase high-performance liquid chromatographic measurement of urinary vanillylmandelic acid in patients with neural crest tumors.

A rapid and simple reversed-phase high-performance liquid chromatographic procedure for the determination of vanillylmandelic acid (VMA) is described. This method was applied in the determination of the VMA content in urine from normal subjects and patients with neural crest lesions. Sample preparation is minimal and the analysis is short (20 min) and reproducible. The sensitivity of the UV detection is in the ng range. By this technique, fourteen adult control subjects were found to excrete a mean of 2.86 microgram VMA per mg creatinine, whereas twelve patients with pheochromocytoma excreted a mean of 15.7 microgram VMA per mg creatinine.

Chromatography, High Pressure Liquid

Pigmented ganglioneuroblastoma: relation of melanin and lipofuscin to schwannomas and other tumors of neural crest origin.

An unusual case of ganglioneuroblastoma containing melanin is presented. Electron microscopy revealed various stages of development of melanosomes in neoplastic cells of Schwann, the first direct demonstration in human material that these cells are malanogenic. The frequent occurrence of neuromelanin in autonomic ganglia and in ganglioneuromas is interpreted as the presence of altered lipofuscin. Review of ultrastructural and other observations indicates a relation between various pigmented tumors, the cell of Schwann, and other cells arising from the neural crest.

Adolescent

Ultrastructural evidence for neural crest origin of the malanotic neuroectodermal tumor of infancy.

A case of malanotic neuroectodermal tumor of infancy, which occurred in the anterior maxilla of a 3-month-old girl, was studied by electron microscopy. Polymorphic cellular elements were revealed to be present: large melanin-producing cells with some of the characteristics of a neuroepithelium, small non-pigmented cells resembling immature neuroblasts, and many intermediate forms resembling differentiating neuroblasts. All cell types clearly demonstrated ultrastructural features of neurogenic cells, e.g. neurite-like cytoplasmic processes, fine filaments and microtubules indistinguishable from those seen in normal neurites, synaptic-like structures, and neurosecretory-like vesicles. Based on these fine structures, the lesion was presumed to represent a hamartoma of primitive neuroectodermal cells with a tendency toward the differentiation into melanin-producing cells. The neural crest origin of this tumor was convincingly supported by ultrastructural analysis.

Cell Nucleolus