RESUMEN
The cardiac outflow tract (OFT) transiently links the ventricles to the aortic sac and forms the arterial valves. Abnormalities in these valves, such as bicuspid aortic valve (BAV), are common congenital anomalies. GATA6-inactivating variants cause cardiac OFT defects and BAV, but their mechanisms are unclear. We generated Gata6STOP/+ mice using CRISPR-Cas9, which show highly penetrant BAV (70%) and membranous ventricular septal defects (43%). These mice exhibited decreased proliferation and increased ISL1-positive progenitor cells in the OFT, indicating abnormal cardiovascular differentiation. Gata6 deletion with the Mef2cCre driver line recapitulated Gata6STOP/+ phenotypes, indicating a cell-autonomous role for Gata6 in the second heart field. Gata6STOP/+ mice showed reduced OFT length and caliber, associated with deficient cardiac neural crest cell contribution, which may cause valvulo-septal defects. RNA-sequencing analysis showed depletion in pathways related to cell proliferation and migration, highlighting Cxcr7 (also known as Ackr3) as a candidate gene. Reduced mesenchymal cell migration and invasion were observed in Gata6STOP/+ OFT tissue. CXCR7 agonists reduced mesenchymal cell migration and increased invasion in wild-type but not in Gata6STOP/+ explants, indicating the GATA6-dependent role of CXCR7 in OFT development and its potential link to BAV.
Asunto(s)
Enfermedad de la Válvula Aórtica Bicúspide , Proliferación Celular , Factor de Transcripción GATA6 , Receptores CXCR , Transducción de Señal , Animales , Factor de Transcripción GATA6/metabolismo , Factor de Transcripción GATA6/genética , Enfermedad de la Válvula Aórtica Bicúspide/patología , Receptores CXCR/metabolismo , Receptores CXCR/genética , Cresta Neural/metabolismo , Cresta Neural/patología , Ratones , Movimiento Celular , Válvula Aórtica/anomalías , Válvula Aórtica/patología , Válvula Aórtica/metabolismo , Enfermedades de las Válvulas Cardíacas/patología , Enfermedades de las Válvulas Cardíacas/metabolismo , Enfermedades de las Válvulas Cardíacas/genética , Fenotipo , Ratones Endogámicos C57BLRESUMEN
The problem of the origin of the bony shell in turtles has a two-century history and still has not lost its relevance. First, this concerns the issues of the homology, the sources of formation and the ratio of bones of different nature, that is, thecal and epithecal, in particular. This article analyzes various views on the nature of the shell elements, and proposes their typification, based on modern data on developmental biology. It is proposed that the defining characteristic of the types of shell ossifications is not the level of their anlage in the dermis (thecality or epithecality), but, first of all, the primary sources of their formation: (1) neural crest (nuchal and plastral plates); (2) vertebral and rib periosteum (neural and costal plates); and (3) dermal mesenchyme (peripheral, suprapygal and pygal plates, as well as epithecal elements). In addition, there is complete correspondence between these types of ossifications and the sequence of their appearance in the turtle ontogenesis. The data show fundamental coincidence of the modifications of the ontogenetic development and evolutionary formation of the shell ossifications and are in agreement with a stepwise model for the origin of the turtle body plan. Particular attention is paid to the origin of the epithecal elements of the turtle shell, which correspond to the additional or supernumerary ossifications and seem to have wider distribution among turtles, than previously thought.
Asunto(s)
Exoesqueleto , Osteogénesis , Filogenia , Tortugas , Animales , Tortugas/anatomía & histología , Tortugas/embriología , Exoesqueleto/anatomía & histología , Exoesqueleto/crecimiento & desarrollo , Exoesqueleto/embriología , Osteogénesis/fisiología , Evolución Biológica , Cresta Neural/embriología , Mesodermo/embriologíaRESUMEN
A complete understanding of neural crest cell mechanodynamics during ocular development will provide insight into postnatal neural crest cell contributions to ophthalmic abnormalities in adult tissues and inform regenerative strategies toward injury repair. Herein, single-cell RNA sequencing in zebrafish during early eye development revealed keratin intermediate filament genes krt8 and krt18a.1 as additional factors expressed during anterior segment development. In situ hybridization and immunofluorescence microscopy confirmed krt8 and krt18a.1 expression in the early neural plate border and migrating cranial neural crest cells. Morpholino oligonucleotide (MO)-mediated knockdown of K8 and K18a.1 markedly disrupted the migration of neural crest cell subpopulations and decreased neural crest cell marker gene expression in the craniofacial region and eye at 48 h postfertilization (hpf), resulting in severe phenotypic defects reminiscent of neurocristopathies. Interestingly, the expression of K18a.1, but not K8, is regulated by retinoic acid (RA) during early-stage development. Further, both keratin proteins were detected during postnatal corneal regeneration in adult zebrafish. Altogether, we demonstrated that both K8 and K18a.1 contribute to the early development and postnatal repair of neural crest cell-derived ocular tissues.
Asunto(s)
Córnea , Queratina-8 , Cresta Neural , Regeneración , Pez Cebra , Animales , Pez Cebra/genética , Pez Cebra/metabolismo , Cresta Neural/metabolismo , Cresta Neural/citología , Queratina-8/metabolismo , Queratina-8/genética , Córnea/metabolismo , Regulación del Desarrollo de la Expresión Génica/efectos de los fármacos , Proteínas de Pez Cebra/metabolismo , Proteínas de Pez Cebra/genética , Queratina-18/metabolismo , Queratina-18/genética , Tretinoina/farmacología , Tretinoina/metabolismo , Movimiento Celular/genéticaRESUMEN
The sympathetic nervous system controls bodily functions including vascular tone, cardiac rhythm, and the "fight-or-flight response". Sympathetic chain ganglia develop in parallel with preganglionic motor nerves extending from the neural tube, raising the question of whether axon targeting contributes to sympathetic chain formation. Using nerve-selective genetic ablations and lineage tracing in mouse, we reveal that motor nerve-associated Schwann cell precursors (SCPs) contribute sympathetic neurons and satellite glia after the initial seeding of sympathetic ganglia by neural crest. Motor nerve ablation causes mispositioning of SCP-derived sympathoblasts as well as sympathetic chain hypoplasia and fragmentation. Sympathetic neurons in motor-ablated embryos project precociously and abnormally towards dorsal root ganglia, eventually resulting in fusion of sympathetic and sensory ganglia. Cell interaction analysis identifies semaphorins as potential motor nerve-derived signaling molecules regulating sympathoblast positioning and outgrowth. Overall, central innervation functions both as infrastructure and regulatory niche to ensure the integrity of peripheral ganglia morphogenesis.
Asunto(s)
Ganglios Simpáticos , Neuronas Motoras , Cresta Neural , Células de Schwann , Sistema Nervioso Simpático , Animales , Sistema Nervioso Simpático/embriología , Ratones , Neuronas Motoras/fisiología , Células de Schwann/metabolismo , Cresta Neural/citología , Cresta Neural/metabolismo , Ganglios Simpáticos/citología , Ganglios Espinales , Semaforinas/metabolismo , Semaforinas/genética , Ratones Transgénicos , Neuroglía/metabolismo , FemeninoRESUMEN
Melanocytes evolved to produce the melanin that gives colour to our hair, eyes and skin. The melanocyte lineage also gives rise to melanoma, the most lethal form of skin cancer. The melanocyte lineage differentiates from neural crest cells during development, and most melanocytes reside in the skin and hair, where they are replenished by melanocyte stem cells. Because the molecular mechanisms necessary for melanocyte specification, migration, proliferation and differentiation are co-opted during melanoma initiation and progression, studying melanocyte development is directly relevant to human disease. Here, through the lens of advances in cellular omic and genomic technologies, we review the latest findings in melanocyte development and differentiation, and how these developmental pathways become dysregulated in disease.
Asunto(s)
Diferenciación Celular , Linaje de la Célula , Melanocitos , Melanoma , Melanocitos/metabolismo , Melanocitos/citología , Humanos , Animales , Melanoma/patología , Melanoma/metabolismo , Melanoma/genética , Cresta Neural/metabolismo , Proliferación Celular , Neoplasias Cutáneas/patología , Neoplasias Cutáneas/metabolismo , Neoplasias Cutáneas/genéticaRESUMEN
Vertebrate calcitonin-producing cells (C-cells) are neuroendocrine cells that secrete the small peptide hormone calcitonin in response to elevated blood calcium levels. Whereas mouse C-cells reside within the thyroid gland and derive from pharyngeal endoderm, avian C-cells are located within ultimobranchial glands and have been reported to derive from the neural crest. We use a comparative cell lineage tracing approach in a range of vertebrate model systems to resolve the ancestral embryonic origin of vertebrate C-cells. We find, contrary to previous studies, that chick C-cells derive from pharyngeal endoderm, with neural crest-derived cells instead contributing to connective tissue intimately associated with C-cells in the ultimobranchial gland. This endodermal origin of C-cells is conserved in a ray-finned bony fish (zebrafish) and a cartilaginous fish (the little skate, Leucoraja erinacea). Furthermore, we discover putative C-cell homologs within the endodermally-derived pharyngeal epithelium of the ascidian Ciona intestinalis and the amphioxus Branchiostoma lanceolatum, two invertebrate chordates that lack neural crest cells. Our findings point to a conserved endodermal origin of C-cells across vertebrates and to a pre-vertebrate origin of this cell type along the chordate stem.
Asunto(s)
Calcitonina , Linaje de la Célula , Ciona intestinalis , Endodermo , Cresta Neural , Células Neuroendocrinas , Animales , Endodermo/metabolismo , Endodermo/citología , Calcitonina/metabolismo , Células Neuroendocrinas/metabolismo , Células Neuroendocrinas/citología , Ciona intestinalis/metabolismo , Ciona intestinalis/embriología , Cresta Neural/metabolismo , Cresta Neural/citología , Embrión de Pollo , Ratones , Vertebrados/embriología , Vertebrados/metabolismo , Pez Cebra/embriología , Anfioxos/embriología , Anfioxos/metabolismo , Anfioxos/genética , Cuerpo Ultimobranquial/metabolismoRESUMEN
Larvacean tunicates feature a spectacular innovation not seen in other animals - the trunk oikoplastic epithelium (OE). This epithelium produces a house, a large and complex extracellular structure used for filtering and concentrating food particles. Previously we identified several homeobox transcription factor genes expressed during early OE patterning. Among these are two Pax3/7 copies that we named pax37A and pax37B. The vertebrate homologs, PAX3 and PAX7 are involved in developmental processes related to neural crest and muscles. In the ascidian tunicate Ciona intestinalis, Pax3/7 plays a role in the development of cells deriving from the neural plate border, including trunk epidermal sensory neurons and tail nerve cord neurons, as well as in the neural tube closure. Here we have investigated the roles of Oikopleura dioica pax37A and pax37B in the development of the OE, by using CRISPR-Cas9 mutant lines and analyzing scRNA-seq data from wild-type animals. We found that pax37B but not pax37A is essential for the differentiation of cell fields that produce the food concentrating filter of the house: the anterior Fol, giant Fol and Nasse cells. Trajectory analysis supported a neuroepithelial-like or a preplacodal ectoderm transcriptional signature in these cells. We propose that the highly specialized secretory epithelial cells of the Fol region either maintained or evolved neuroepithelial features. This is supported by a fragmented gene regulatory network involved in their development that also operates in ascidian epidermal neurons.
Asunto(s)
Factor de Transcripción PAX3 , Factor de Transcripción PAX7 , Urocordados , Animales , Urocordados/embriología , Urocordados/genética , Factor de Transcripción PAX7/genética , Factor de Transcripción PAX7/metabolismo , Factor de Transcripción PAX3/genética , Factor de Transcripción PAX3/metabolismo , Regulación del Desarrollo de la Expresión Génica/genética , Epitelio/metabolismo , Ciona intestinalis/genética , Ciona intestinalis/embriología , Diferenciación Celular/genética , Cresta Neural/metabolismo , Cresta Neural/embriologíaRESUMEN
Mesenchymal stromal cells (MSCs) display heterogeneity in origin and functional role in tissue homeostasis. Subsets of MSCs derived from the neural crest express nestin and serve as niches in bone marrow, but the possibility of coaxing MSCs into nestin-expresing cells for enhanced supportive activity is unclear. In this study, as an approach to the chemical coaxing of MSC functions, we screened libraries of clinically approved chemicals to identify compounds capable of inducing nestin expression in MSCs. Out of 2000 clinical compounds, we chose vorinostat as a candidate to coax the MSCs into neural crest-like fates. When treated with vorinostat, MSCs exhibited a significant increase in the expression of genes involved in the pluripotency and epithelial-mesenchymal transition (EMT), as well as nestin and CD146, the markers for pericytes. In addition, these nestin-induced MSCs exhibited enhanced differentiation towards neuronal cells with the upregulation of neurogenic markers, including SRY-box transcription factor 2 (Sox2), SRY-box transcription factor 10 (Sox10) and microtubule associated protein 2 (Map2) in addition to nestin. Moreover, the coaxed MSCs exhibited enhanced supporting activity for hematopoietic progenitors without supporting leukemia cells. These results demonstrate the feasibility of the drug repositioning of MSCs to induce neural crest-like properties through the chemical coaxing of cell fates.
Asunto(s)
Diferenciación Celular , Reposicionamiento de Medicamentos , Células Madre Mesenquimatosas , Nestina , Células Madre Mesenquimatosas/efectos de los fármacos , Células Madre Mesenquimatosas/metabolismo , Células Madre Mesenquimatosas/citología , Nestina/metabolismo , Nestina/genética , Humanos , Diferenciación Celular/efectos de los fármacos , Reposicionamiento de Medicamentos/métodos , Transición Epitelial-Mesenquimal/efectos de los fármacos , Células Cultivadas , Cresta Neural/citología , Cresta Neural/metabolismo , Cresta Neural/efectos de los fármacosRESUMEN
Epithelial-Mesenchymal Transition (EMT) is a key process in physiological and pathological settings. EMT is often presented as a linear sequence with (i) disassembly of cell-cell junctions, (ii) loss of epithelial polarity and (iii) reorganization of the cytoskeleton leading to basal extrusion from the epithelium. Once out, cells can adopt a migratory phenotype with a front-rear polarity. While this sequence can occur, in vivo observations have challenged it. It is now accepted that multiple EMT scenarios coexist in heterogeneous cell populations. However, the relative importance of each step as well as that of variability and heterogeneity on the efficiency of cell extrusion has not been assessed. Here we used computational modelling to simulate multiple EMT-like scenarios and confronted these data to the EMT of neural crest cells. Overall, our data point to a key role of nuclear positioning and protrusive activity to generate timely basal extrusion.
Asunto(s)
Núcleo Celular , Transición Epitelial-Mesenquimal , Núcleo Celular/metabolismo , Animales , Modelos Biológicos , Simulación por Computador , Cresta Neural/citología , Movimiento Celular/fisiología , Humanos , Polaridad Celular/fisiología , Citoesqueleto/metabolismo , Células Epiteliales/metabolismo , Células Epiteliales/citologíaRESUMEN
Cancer cellular heterogeneity and therapy resistance arise substantially from metabolic and transcriptional adaptations, but how these are interconnected is poorly understood. Here, we show that, in melanoma, the cancer stem cell marker aldehyde dehydrogenase 1A3 (ALDH1A3) forms an enzymatic partnership with acetyl-coenzyme A (CoA) synthetase 2 (ACSS2) in the nucleus to couple high glucose metabolic flux with acetyl-histone H3 modification of neural crest (NC) lineage and glucose metabolism genes. Importantly, we show that acetaldehyde is a metabolite source for acetyl-histone H3 modification in an ALDH1A3-dependent manner, providing a physiologic function for this highly volatile and toxic metabolite. In a zebrafish melanoma residual disease model, an ALDH1-high subpopulation emerges following BRAF inhibitor treatment, and targeting these with an ALDH1 suicide inhibitor, nifuroxazide, delays or prevents BRAF inhibitor drug-resistant relapse. Our work reveals that the ALDH1A3-ACSS2 couple directly coordinates nuclear acetaldehyde-acetyl-CoA metabolism with specific chromatin-based gene regulation and represents a potential therapeutic vulnerability in melanoma.
Asunto(s)
Acetaldehído , Melanoma , Pez Cebra , Melanoma/metabolismo , Melanoma/genética , Melanoma/patología , Melanoma/tratamiento farmacológico , Acetaldehído/metabolismo , Acetaldehído/farmacología , Animales , Humanos , Línea Celular Tumoral , Aldehído Oxidorreductasas/metabolismo , Aldehído Oxidorreductasas/genética , Histonas/metabolismo , Coenzima A Ligasas/metabolismo , Coenzima A Ligasas/genética , Transcripción Genética/efectos de los fármacos , Cresta Neural/metabolismo , Cresta Neural/efectos de los fármacos , Regulación Neoplásica de la Expresión Génica/efectos de los fármacosRESUMEN
The trigeminal ganglion, the largest of the vertebrate cranial ganglia, is comprised of sensory neurons that relay sensations of pain, touch, and temperature to the brain. These neurons are derived from two embryonic cell types, the neural crest and ectodermal placodes, whose interactions are critical for proper ganglion formation. While the T-cell leukemia homeobox 3 (Tlx3) gene is known to be expressed in placodally-derived sensory neurons and necessary for their differentiation, little was known about Tlx3 expression and/or function in the neural crest-derived component of the developing trigeminal ganglion. By combining lineage labeling with in situ hybridization in the chick embryo, we show that neural crest-derived cells that contribute to the cranial trigeminal ganglion express Tlx3 at a time point that coincides with the onset of ganglion condensation. Importantly, loss of Tlx3 function in vivo diminishes the overall size and abundance of neurons within the trigeminal ganglion. Conversely, ectopic expression of Tlx3 in migrating cranial neural crest results in their premature neuronal differentiation. Taken together, our results demonstrate a critical role for Tlx3 in neural crest-derived cells during chick trigeminal gangliogenesis.
Asunto(s)
Diferenciación Celular , Regulación del Desarrollo de la Expresión Génica , Proteínas de Homeodominio , Cresta Neural , Ganglio del Trigémino , Animales , Ganglio del Trigémino/metabolismo , Ganglio del Trigémino/embriología , Ganglio del Trigémino/citología , Embrión de Pollo , Cresta Neural/metabolismo , Cresta Neural/embriología , Cresta Neural/citología , Proteínas de Homeodominio/metabolismo , Proteínas de Homeodominio/genética , Neuronas/metabolismo , Neurogénesis/genética , Movimiento Celular , Linaje de la CélulaRESUMEN
The somatosensory system detects peripheral stimuli that are translated into behaviors necessary for survival. Fishes and amphibians possess two somatosensory systems in the trunk: the primary somatosensory system, formed by the Rohon-Beard neurons, and the secondary somatosensory system, formed by the neural crest cell-derived neurons of the Dorsal Root Ganglia. Rohon-Beard neurons have been characterized as a transient population that mostly disappears during the first days of life and is functionally replaced by the Dorsal Root Ganglia. Here, I follow Rohon-Beard neurons in vivo and show that the entire repertoire remains present in zebrafish from 1-day post-fertilization until the juvenile stage, 15-days post-fertilization. These data indicate that zebrafish retain two complete somatosensory systems until at least a developmental stage when the animals display complex behavioral repertoires.
Asunto(s)
Pez Cebra , Animales , Pez Cebra/embriología , Ganglios Espinales/embriología , Neuronas/fisiología , Cresta Neural/citología , Cresta Neural/embriología , Cresta Neural/fisiologíaRESUMEN
Goldenhar syndrome, a rare craniofacial malformation, is characterized by developmental anomalies in the first and second pharyngeal arches. Its etiology is considered to be heterogenous, including both genetic and environmental factors that remain largely unknown. To further elucidate the genetic cause in a five-generation Goldenhar syndrome pedigree and exploit the whole-exome sequencing (WES) data of this pedigree, we generated collapsed haplotype pattern markers based on WES and employed rare variant nonparametric linkage analysis. FBLN2 was identified as a candidate gene via analysis of WES data across the significant linkage region. A fbln2 knockout zebrafish line was established by CRISPR/Cas9 to examine the gene's role in craniofacial cartilage development. fbln2 was expressed specifically in the mandible during the zebrafish early development, while fbln2 knockout zebrafish exhibited craniofacial malformations with abnormal chondrocyte morphologies. Functional studies revealed that fbln2 knockout caused abnormal chondrogenic differentiation, apoptosis, and proliferation of cranial neural crest cells (CNCCs), and downregulated the bone morphogenic protein (BMP) signaling pathway in the zebrafish model. This study demonstrates the role of FBLN2 in CNCC development and BMP pathway regulation, and highlights FBLN2 as a candidate gene for Goldenhar syndrome, which may have implications for the selection of potential screening targets and the development of treatments for conditions like microtia-atresia.
Asunto(s)
Síndrome de Goldenhar , Cresta Neural , Linaje , Pez Cebra , Animales , Pez Cebra/embriología , Pez Cebra/genética , Cresta Neural/metabolismo , Síndrome de Goldenhar/genética , Síndrome de Goldenhar/metabolismo , Síndrome de Goldenhar/patología , Humanos , Femenino , Masculino , Diferenciación Celular/genética , Secuenciación del Exoma , Condrogénesis/genética , Transducción de Señal/genética , Proteínas de Pez Cebra/genética , Proteínas de Pez Cebra/metabolismo , Proteínas Morfogenéticas Óseas/metabolismo , Proteínas Morfogenéticas Óseas/genéticaRESUMEN
Over the years, the origin of ovarian Leydig cells has been, and still is, a topic subject to deep debate. Seven years ago, we proposed that this origin resided in intraneural elements that came from a possible reservoir of neural crest cells, a reservoir that may be located in the ganglia of the celiac plexus. We believe we have found the evidence necessary to prove this hypothesis.
Asunto(s)
Células Intersticiales del Testículo , Ovario , Femenino , Células Intersticiales del Testículo/citología , Células Intersticiales del Testículo/fisiología , Humanos , Ovario/citología , Animales , Cresta Neural/citología , Ganglios Simpáticos/citologíaRESUMEN
Cells have evolved mechanisms to migrate for diverse biological functions. A process frequently deployed during metazoan cell migration is the epithelial-mesenchymal transition (EMT). During EMT, adherent epithelial cells undergo coordinated cellular transitions to mesenchymalize and reduce their intercellular attachments. This is achieved via tightly regulated changes in gene expression, which modulates cell-cell and cell-matrix adhesion to allow movement. The acquisition of motility and invasive properties following EMT allows some mesenchymal cells to migrate through complex environments to form tissues during embryogenesis; however, these processes may also be leveraged by cancer cells, which often co-opt these endogenous programs to metastasize. Post-transcriptional regulation is now emerging as a major conserved mechanism by which cells modulate EMT and migration, which we discuss here in the context of vertebrate development and cancer.
Asunto(s)
Movimiento Celular , Transición Epitelial-Mesenquimal , Neoplasias , Cresta Neural , Cresta Neural/metabolismo , Cresta Neural/citología , Humanos , Animales , Neoplasias/metabolismo , Neoplasias/patología , Neoplasias/genética , Procesamiento Postranscripcional del ARNRESUMEN
OBJECTIVES: This study aimed to explore the heterogeneity and gene ontology of Wnt1-Cre-marked and Pax2-Cre-marked first branchial arch cranial neural crest cells (CNCs) in mice. METHODS: The embryos of Wnt1-Cre;R26RmTmG and Pax2-Cre;R26RmTmG at embryonic day (E)8.0-E9.25 were collected for histological observation. We performed immunostaining to compare green fluorescent protein (GFP)-positive CNCs in Pax2-Cre;R26RAi9 and Wnt1-Cre;R26RAi9 mice at E15.5. Single-cell RNA sequencing (scRNA-seq) was used to analyze the first branchial arch GFP-positive CNCs from Wnt1-Cre;R26RmTmG and Pax2-cre;R26RmTmGmice at E10.5. Real time fluorescence quantitative polymerase chain reaction (q-PCR) was performed to validate the differential genes. RESULTS: Wnt1-Cre-marked and Pax2-Cre-marked CNCs migrated from the neural plateto first and second branchial arches and to the first branchial arch, respectively, at E8.0. Although Wnt1-Cre-marked and Pax2-Cre-marked CNCs were found mostly in cranial-facial tissues, the former had higher expression in palate and tongue. The results of scRNA-seq showed that Pax2-Cre-marked CNCs specifically contributed to osteoblast differentiation and ossification, while Wnt1-Cre-marked CNCs participated in limb development, cell migration, and ossification. The q-PCR data also confirmed the results of gene ontology analysis. CONCLUSIONS: Pax2-Cre mice are perfect experimental animal models for research on first branchial arch CNCs and derivatives in osteoblast differentiation and ossification.
Asunto(s)
Región Branquial , Cresta Neural , Factor de Transcripción PAX2 , Proteína Wnt1 , Animales , Cresta Neural/metabolismo , Ratones , Proteína Wnt1/metabolismo , Factor de Transcripción PAX2/metabolismo , Integrasas/metabolismo , Proteínas Fluorescentes Verdes/metabolismoRESUMEN
The neural crest is a vertebrate-specific stem cell population that helped drive the origin and evolution of vertebrates. A distinguishing feature of these cells is their multi-germ layer potential, which has parallels to another stem cell population-pluripotent stem cells of the vertebrate blastula. Here, we investigate the evolutionary origins of neural crest potential by comparing neural crest and pluripotency gene regulatory networks of a jawed vertebrate, Xenopus, and a jawless vertebrate, lamprey. We reveal an ancient evolutionary origin of shared regulatory factors in these gene regulatory networks that dates to the last common ancestor of extant vertebrates. Focusing on the key pluripotency factor pou5, we show that a lamprey pou5 orthologue is expressed in animal pole cells but is absent from neural crest. Both lamprey and Xenopus pou5 promote neural crest formation, suggesting that pou5 activity was lost from the neural crest of jawless vertebrates or acquired along the jawed vertebrate stem. Finally, we provide evidence that pou5 acquired novel, neural crest-enhancing activity after evolving from an ancestral pou3-like clade. This work provides evidence that both the neural crest and blastula pluripotency networks arose at the base of the vertebrates and that this may be linked to functional evolution of pou5.
Asunto(s)
Evolución Biológica , Blástula , Lampreas , Cresta Neural , Xenopus , Animales , Cresta Neural/citología , Lampreas/genética , Blástula/citología , Vertebrados , Redes Reguladoras de GenesRESUMEN
The bromodomain and extra-terminal (BET) family of proteins reads epigenetic histone acetylation marks on the genome and regulates the transcriptional machinery. In their study, Carole LaBonne and colleagues reveal the role of BET protein activity in the maintenance of pluripotency and establishment of the neural crest in Xenopus laevis. To know more about their work, we spoke to the first author Paul Huber and the corresponding author Carole LaBonne, Developmental and Stem Cell Biologist at Northwestern University.
Asunto(s)
Xenopus laevis , Animales , Historia del Siglo XXI , Humanos , Historia del Siglo XX , Cresta Neural/metabolismo , Biología Evolutiva/historiaRESUMEN
This study aimed to assess the impact of conditioned medium from epidermal neural crest stem cells (EPI-NCSCs-CM) on functional recovery following spinal cord injury (SCI), while also exploring the involvement of the PI3K-AKT signaling pathway in regulating neuronal apoptosis. EPI-NCSCs were isolated from 10-day-old Sprague-Dawley rats and cultured for 48 h to obtain EPI-NCSC-CM. SHSY-5Y cells were subjected with H2O2 treatment to induce apoptosis. Cell viability and survival rates were evaluated using the CCK-8 assay and calcein-AM/PI staining. SCI contusion model was established in adult Sprague-Dawley rats to assess functional recovery, utilizing the Basso, Beattie and Bresnahan (BBB) scoring system, inclined test, and footprint observation. Neurological restoration after SCI was analyzed through electrophysiological recordings. Histological analysis included hematoxylin and eosin (H&E) staining and Nissl staining to evaluate tissue organization. Apoptosis and oxidative stress levels were assessed using TUNEL staining and ROS detection methods. Additionally, western blotting was performed to examine the expression of apoptotic markers and proteins related to the PI3K/AKT signaling pathway. EPI-NCSC-CM significantly facilitated functional and histological recovery in SCI rats by inhibiting neuronal apoptosis through modulation of the PI3K/AKT pathway. Administration of EPI-NCSCs-CM alleviated H2O2-induced neurotoxicity in SHSY-5Y cells in vitro. The use of LY294002, a PI3K inhibitor, underscored the crucial role of the PI3K/AKT signaling pathway in regulating neuronal apoptosis. This study contributes to the ongoing exploration of molecular pathways involved in spinal cord injury (SCI) repair, focusing on the therapeutic potential of EPI-NCSC-CM. The research findings indicate that EPI-NCSC-CM exerts a neuroprotective effect by suppressing neuronal apoptosis through activation of the PI3K/AKT pathway in SCI rats. These results highlight the promising role of EPI-NCSC-CM as a potential treatment strategy for SCI, emphasizing the significance of the PI3K/AKT pathway in mediating its beneficial effects.
Asunto(s)
Apoptosis , Células-Madre Neurales , Neuronas , Fosfatidilinositol 3-Quinasas , Proteínas Proto-Oncogénicas c-akt , Ratas Sprague-Dawley , Traumatismos de la Médula Espinal , Animales , Traumatismos de la Médula Espinal/tratamiento farmacológico , Traumatismos de la Médula Espinal/metabolismo , Traumatismos de la Médula Espinal/patología , Apoptosis/efectos de los fármacos , Apoptosis/fisiología , Proteínas Proto-Oncogénicas c-akt/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Medios de Cultivo Condicionados/farmacología , Células-Madre Neurales/efectos de los fármacos , Neuronas/efectos de los fármacos , Neuronas/metabolismo , Recuperación de la Función/efectos de los fármacos , Recuperación de la Función/fisiología , Cresta Neural/efectos de los fármacos , Ratas , Transducción de Señal/efectos de los fármacos , MasculinoRESUMEN
During embryonic development, the vertebrate embryonic epiblast is divided into two parts including neural and superficial ectoderm. The neural plate border (NPB) is a narrow transitional area which locates between these parts and contains multipotent progenitor cells. Despite its small size, the cellular heterogeneity in this region produces specific differentiated cells. Signaling pathways, transcription factors, and the expression/repression of certain genes are directly involved in these differentiation processes. Different factors such as the Wnt signaling cascade, fibroblast growth factor (FGF), bone morphogenetic protein (BMP) signaling, and Notch, which are involved in various stages of the growth, proliferation, and differentiation of embryonic cells, are also involved in the determination and differentiation of neural plate border stem cells. Therefore, it is essential to consider the interactions and temporospatial coordination related to cells, tissues, and adjacent structures. This review examines our present knowledge of the formation of the neural plate border and emphasizes the requirement for interaction between different signaling pathways, including the BMP and Wnt cascades, the expression of its special target genes and their regulations, and the precise tissue crosstalk which defines the neural crest fate in the ectoderm at the early human embryonic stages.