ABSTRACT
The morphogenesis of the head of vertebrates is a process that involves rapid growth and dynamic movements of various cell populations, including the neural crest cells (NCC). These pluripotent cells generated during neurulation have high proliferative and migratory capacity but xenobiotic agents can affect these migratory periods and cause congenital malformations. Lead (Pb) is the most common toxic metal in the environment and a potent teratogen that can affect growth and induce malformations. Despite the known toxic effects of Pb, there is a gap in knowledge about the impact of realistic concentrations of Pb at critical periods of early development. Here, we evaluated mortality, embryonic morphology, NCC migration, and the amount of Pb deposition in chicken embryos after 3 to 4 days of exposure. One of the most interesting observations in this study is that only about 34% of the injected Pb was present in the embryos after 4 days. We observed that exposure to Pb, even under low concentrations, increased mortality and the occurrence of malformations during embryonic development, especially in the cephalic region (CR). Although Pb was found widely distributed in the CR, no relation between its presence and the migration routes of cephalic NCC was observed. But the number of NCC and their migratory distance were reduced. These changes are consistent and explain the morphological anomalies described in this study, which also correlates with the morphofunctional abnormalities reported in the literature. Therefore, this study highlights the concern of exposure to low concentrations of this metal.
Subject(s)
Lead Poisoning, Nervous System/pathology , Neural Crest/pathology , Abnormalities, Drug-Induced/pathology , Animals , Biological Availability , Brain/abnormalities , Brain/pathology , Cell Movement , Chick Embryo , Embryonic Development/drug effects , Lead/metabolism , Lead/pharmacokinetics , Lead/toxicity , Lead Poisoning, Nervous System/mortality , Morphogenesis , Nitrates/toxicityABSTRACT
RESUMEN Las células de la cresta neural son pluripotenciales y son llamadas la cuarta hoja germinativa del embrión. Con el objetivo de estructurar los referentes teóricos actualizados que sustenten la afirmación precedente y que constituirá material de estudio para los estudiantes de las Ciencias Médicas, se realizó la revisión de 28 referencias bibliográficas, de ellas 89% actualizadas. Estas células aparecen durante la neurulación y pasado este proceso transitan de epitelial a mesenquimatosa; migran siguiendo señales de la matriz extracelular a todo el cuerpo del embrión diferenciándose en tejidos disimiles. Muy vinculados en su evolución a mecanismos epigenéticos, hacen a esta población celular vulnerables a ser dañadas invocándose en la etiología de diferentes defectos congénitos y enfermedades crónicas no trasmisibles como cáncer. Como conclusión por su pluripotencialidad y por los mecanismos moleculares que distinguen su evolución son consideradas por muchos autores la cuarta hoja germinativa del embrión (AU).
SUMMARY Neural crest cells are pluripotentials, and are called the fourth germinative leaf of the embryo. With the objective of structuring the updated theoretical referents backing up the precedent affirmation that will be study material for the students of Medical Sciences, the authors reviewed 28 bibliographic references, 89 % of them updated. These cells appear during neurulation and after this process they transit from epithelial to mesenchymal; following extracellular matrix signals, they migrate to the whole embryo body differentiating themselves in dissimilar tissues. Tightly related in their evolution to epigenetic mechanisms, this cell population is very likely to be damaged and so they are invoked in the etiology of different congenital defects and noncommunicable chronic diseases like cancer. In conclusion, due to their pluripotentiality and the molecular mechanisms distinguishing their evolution, many authors consider them the embryo´s fourth germinative leaf (AU).
Subject(s)
Humans , Male , Female , Cells/metabolism , Neural Crest/pathology , Students, Medical , Vertebrates/genetics , Neurulation/physiology , Neural Crest/abnormalities , Neural Crest/physiology , Neural Crest/physiopathologyABSTRACT
Traditionally, the cartilaginous viscerocranium of vertebrates is considered as neural crest (NC)-derived. Morphological work carried out on amphibian embryos in the first half of the XX century suggested potentially mesodermal origin for some hyobranchial elements. Since then, the embryonic sources of the hyobranchial apparatus in amphibians has not been investigated due to lack of an appropriate long-term labelling system. We performed homotopic transplantations of neural folds along with the majority of cells of the presumptive NC, and/or fragments of the head lateral plate mesoderm (LPM) from transgenic GFP+ into white embryos. In these experiments, the NC-derived GFP+ cells contributed to all hyobranchial elements, except for basibranchial 2, whereas the grafting of GFP+ head mesoderm led to a reverse labelling result. The grafting of only the most ventral part of the head LPM resulted in marking of the basibranchial 2 and the heart myocardium, implying their origin from a common mesodermal region. This is the first evidence of contribution of LPM of the head to cranial elements in any vertebrate. If compared to fish, birds, and mammals, in which all branchial skeletal elements are NC-derived, the axolotl (probably this is true for all amphibians) demonstrates an evolutionary deviation, in which the head LPM replaces NC cells in a hyobranchial element. This implies that cells of different embryonic origin may have the same developmental program, leading to the formation of identical (homologous) elements of the skeleton.
Subject(s)
Ambystoma mexicanum/embryology , Ambystoma mexicanum/physiology , Animals , Animals, Genetically Modified , Birds , Bone and Bones/embryology , Cartilage/embryology , Fishes , Green Fluorescent Proteins/chemistry , Green Fluorescent Proteins/metabolism , Head/embryology , Heart/embryology , Mesoderm/embryology , Mesoderm/metabolism , Mesoderm/physiology , Myocardium/pathology , Neural Crest/metabolism , Neural Crest/pathologyABSTRACT
Treacher Collins syndrome (TCS) is an autosomal dominant disorder of craniofacial development, and mutations in the TCOF1 gene are responsible for over 90% of TCS cases. The knowledge about the molecular mechanisms responsible for this syndrome is relatively scant, probably due to the difficulty of reproducing the pathology in experimental animals. Zebrafish is an emerging model for human disease studies, and we therefore assessed it as a model for studying TCS. We identified in silico the putative zebrafish TCOF1 ortholog and cloned the corresponding cDNA. The derived polypeptide shares the main structural domains found in mammals and amphibians. Tcof1 expression is restricted to the anterior-most regions of zebrafish developing embryos, similar to what happens in mouse embryos. Tcof1 loss-of-function resulted in fish showing phenotypes similar to those observed in TCS patients, and enabled a further characterization of the mechanisms underlying craniofacial malformation. Besides, we initiated the identification of potential molecular targets of treacle in zebrafish. We found that Tcof1 loss-of-function led to a decrease in the expression of cellular proliferation and craniofacial development. Together, results presented here strongly suggest that it is possible to achieve fish with TCS-like phenotype by knocking down the expression of the TCOF1 ortholog in zebrafish. This experimental condition may facilitate the study of the disease etiology during embryonic development.
Subject(s)
Disease Models, Animal , Mandibulofacial Dysostosis/genetics , Mandibulofacial Dysostosis/metabolism , Phosphoproteins/genetics , Phosphoproteins/metabolism , Zebrafish Proteins/genetics , Zebrafish Proteins/metabolism , Zebrafish , Amino Acid Sequence , Animals , Cell Movement , Cell Size , Computational Biology , Face/embryology , Gene Expression Regulation, Developmental , Gene Knockdown Techniques , Humans , Mandibulofacial Dysostosis/pathology , Mice , Molecular Sequence Data , Neural Crest/metabolism , Neural Crest/pathology , Phenotype , Phosphoproteins/chemistry , Phosphoproteins/deficiency , Sequence Homology, Amino Acid , Skull/embryology , Skull/metabolism , Time Factors , Zebrafish/embryology , Zebrafish/genetics , Zebrafish/metabolism , Zebrafish Proteins/chemistry , Zebrafish Proteins/deficiencyABSTRACT
In most homeothermic vertebrates, pigment cells are confined to the skin. Recent studies show that the fate-restricted melanoblast (pigment cell precursor) is the only neural crest lineage that can exploit the dorsolateral path between the ectoderm and somite into the dermis, thereby excluding neurons and glial cells from the skin. This does not explain why melanoblasts do not generally migrate ventrally into the region where neurons and glial cell derivatives of the neural crest differentiate, or why melanoblasts do not escape from the dorsolateral path once they have arrived at this destination. To answer these questions we have studied melanogenesis in the Silkie fowl, which is a naturally occurring chicken mutant in which pigment cells occupy most connective tissues, thereby giving them a dramatic blue-black cast. By using markers for neural crest cells (HNK-1) and melanoblasts (Smyth line serum), we have documented the development of the Silkie pigment pattern. The initial dispersal of melanoblasts is the same in the Silkie fowl as in Lightbrown Leghorn (LBL), White Leghorn (WLH), and quail embryos. However, by stage 22, when all ventral neural crest cell migration has ceased in the WLH, melanoblasts in the Silkie embryo continue to migrate between the neural tube and somites to occupy the sclerotome. This late ventral migration was confirmed by filling the lumen of the neural tube with DiI at stage 19 and observing the embryos at stage 26. No DiI-labeled cells were observed in the sclerotome of LBL embryos, whereas in the Silkie embryos DiI-filled cells were found as far ventral as the mesentery. In addition to this extensive ventral migration, we also observed considerable migration of melanoblasts from the distal end of the dorsolateral space into the somatic mesoderm (the future parietal peritoneum), and into the more medioventral regions where they accumulated around the dorsal aorta and the kidney. The ability of melanoblasts in the Silkie embryos to migrate ventrally along the neural tube and medially from the dorsolateral space is correlated with a lack of peanut agglutinin (PNA) -binding barrier tissues, which are present in the LBL embryo. The abnormal pattern of melanoblast migration in the Silkie embryo is further exaggerated by the fact that the melanoblasts continue to divide, as evidenced by BrdU incorporation (but the rate of incorporation is not greater than seen in the LBL). Results from heterospecific grafting studies and cell cultures of WLH and Silkie neural crest cells support the notion that the Silkie phenotype is brought about by an environmental difference rather than a neural crest-specific defect. We conclude that melanoblasts are normally constrained to migrate only in the dorsolateral path, and once in that path they generally do not escape it. We further conclude that the barriers that normally restrain melanoblast migration in the chicken are not present in the Silkie fowl. We are now actively investigating the nature of this barrier molecule to complete our understanding of melanoblast migration and patterning.
Subject(s)
Melanocytes/pathology , Pigmentation Disorders/embryology , Pigmentation Disorders/genetics , Animals , Cell Differentiation/genetics , Cell Division/genetics , Cell Movement/genetics , Cells, Cultured , Chick Embryo , Mutation , Neural Crest/embryology , Neural Crest/pathology , Peanut Agglutinin/metabolism , Phenotype , Pigmentation Disorders/pathology , Quail , Skin Pigmentation/genetics , Stem Cells/pathologyABSTRACT
Los nevi de la úvea son frecuentes (2 por ciento de la población general), pueden localizarse en el iris, cuerpo ciliar o coroides. Los nevi de más fácil diagnóstico son los del iris, que pueden ser únicos o múltiples y en ocasiones originan alteraciones en el aparato de filtración dando como resultado glaucoma (síndrome del nevo del iris). Los del cuerpo ciliar pasan inadvertidos en la mayoría de los casos. Los localizados en la coroides son lesiones frecuentes y se descubren accidentalmente en la fundoscopia. Los melanomas son la forma maligna, los más frecuentes son los de coroides y les siguen los del cuerpo ciliar e iris. El pronóstico depende de muchos factores y el tratamiento es controversial. Los melanocitomas son lesiones benignas aunque ocasionalmente pueden desarrollar cambios a melanoma. Se les localiza en papila y en cuerpo ciliar. El prognoma melanótico es una lesión muy rara propia de la infancia. La hiperplasia de células névicas (melanosis) puede ser congénita o adquirida, primaria y secundaria, las adquiridas y primarias son las que representan mayor riesgo que representan mayor riesgo de epicarcinogénesis.
Subject(s)
Uvea/pathology , Iris/pathology , Melanosis , Neural Crest/pathology , Nevus, Pigmented , APUD Cells , Precancerous Conditions , Choroid/pathology , MelanomaABSTRACT
Hirschsprung disease or aganglionosis coli, is a predominantly pediatric condition, in which there is an innervation defect of the colon, manifested by chronic intermittent constipation alternating with explosive evacuations. The involved colonic segment is unable to relax and acts as an area of obstruction, which causes the proximal segment to dilate enormously. The diagnosis requires participation from several specialties, including pediatric surgery, gastroenterology, radiology and anatomic pathology. In recent years, significant progress in relevant knowledge of this area has been obtained, in particular about defective migration of the neural crest-derived colonic ganglion cell precursors, as well as the genetic aspects of the disease. This article reviews the diagnostic anatomic pathology and the most relevant points about the biology of Hirschsprung disease.
Subject(s)
Hirschsprung Disease , Neural Crest , Biopsy , Cell Differentiation , Colon/pathology , Hirschsprung Disease/diagnosis , Hirschsprung Disease/genetics , Hirschsprung Disease/pathology , Humans , Neural Crest/pathologyABSTRACT
El neuroblastoma es un tumor frecuente en la infancia. Su comportamiento es imprevisible y puede confundirse con otras neoplasias de la infancia. El rastreo con I-Metaiodobenzilguanidina que es un método de diagnóstico y de seguimiento con alta sensibilidad y especificidad para el diagnóstico de tumores derivados de la cresta neural. Se estudiaron 36 pacientes con sospecha de tumor derivado de la cresta neural y tres con diagnóstico histológico de neuroblastoma. En todos se bloqueó la glándula tiroides con 30 mg de lugol. El estudio de I-MIBG se efectuó inicialmente y, en algunos casos, como control. La dosis varió de 18.5 a 22.2 MBq; el rastreo se efectuó con gamma cámara LFVO, con colimador paralelo para 360 Kev. Se efectuó un total de 47 rastreos. En 20 pacientes con diagnóstico histológico de neuroblastoma el rastreo con I-MIBG fue positivo; un caso fue negativo no obstante el cuadro clínico y los marcadores tumorales. En dos pacientes con diagnóstico de feocromocitoma el rastreo fue positivo. En otros tumores derivados de la cresta neural, el rastreo fue negativo. Estos resultados dan una sensibilidad del 95.6 por ciento y especificidad de 94.1 por ciento con valor predictivo de 95.6 por ciento. Concluimos que el rastreo con I-MIBG proporciona información funcional a diferencia de la anatómica que proporciona la tomografía computarizada, el ultrasonido y la resonancia magnética, y es de gran utilidad en el seguimiento de estos pacientes
Subject(s)
Humans , Animals , Male , Infant, Newborn , Infant , Child, Preschool , Child , Adolescent , Neuroblastoma/diagnosis , Pheochromocytoma/diagnosis , Magnetic Resonance Spectroscopy , Tomography, X-Ray Computed , Neural Crest , Neural Crest/pathologyABSTRACT
Se informan los hallazgos clínicos y patológicos de un ectomesenquimoma maligno de partes blandas. Los ectomesenquimomas malignos son tumores compuestos por derivados de la cresta neural y uno o más elementos mesenquimatosos malignos, por lo general rabdomiosarcoma, condrosarcoma, angiosarcoma y liposarcoma maligno y liposarcoma. En esta neoplasia, el tratamiento más adecuado es el quirúrgico, pues la quimioterapia y la radioterapia no parecen modifiar el curso de la enfermedad. En este caso el tratamiento fue quirúrgico, sin datos de actividad tumoral a los 16 meses subsecuentes a la operación.
Subject(s)
Humans , Male , Aged , Liposarcoma/pathology , Mesenchymoma/surgery , Neural Crest/embryology , Retroperitoneal Neoplasms/surgery , Schwann Cells/cytology , Schwann Cells/pathology , Mesenchymoma/pathology , Neural Crest/pathology , Retroperitoneal Neoplasms/pathologyABSTRACT
Se presenta un niño de 10 años de edad con lesiones musculosas dispuestas en arabescos y arremolinadas en tórax; lineales en miembros superiores e inferiores. Esta coexisten con afectación de SNC y compromiso óseo, dentario y ocular, constituyendo el cuadro de Hipomelanosis de Ito. Se efectúa microscopía electrónica para confirmar el diagnóstico. Se hace referencia a características clínicas y evolutivas, puntualizando las diferencias con otros síntomas neurocutáneos
Subject(s)
Humans , Child , Male , Skin Diseases, Genetic/diagnosis , Incontinentia Pigmenti/pathology , Keratinocytes/pathology , Melanocytes/ultrastructure , Nerve Endings/pathology , Pigmentation Disorders/ultrastructure , Abnormalities, Multiple , Diagnosis, Differential , Epilepsy , Incontinentia Pigmenti/diagnosis , Keratinocytes/ultrastructure , Melanocytes/pathology , Nerve Endings/ultrastructure , Neural Crest/pathology , Nevus/diagnosis , Pigmentation Disorders/diagnosis , Pigmentation Disorders/pathologyABSTRACT
Se presenta un niño de 10 años de edad con lesiones musculosas dispuestas en arabescos y arremolinadas en tórax; lineales en miembros superiores e inferiores. Esta coexisten con afectación de SNC y compromiso óseo, dentario y ocular, constituyendo el cuadro de Hipomelanosis de Ito. Se efectúa microscopía electrónica para confirmar el diagnóstico. Se hace referencia a características clínicas y evolutivas, puntualizando las diferencias con otros síntomas neurocutáneos