Cellular transitions during cranial suture establishment in zebrafish.

Cranial sutures separate neighboring skull bones and are sites of bone growth. A key question is how osteogenic activity is controlled to promote bone growth while preventing aberrant bone fusions during skull expansion. Using single-cell transcriptomics, lineage tracing, and mutant analysis in zebrafish, we uncover key developmental transitions regulating bone formation at sutures during skull expansion. In particular, we identify a subpopulation of mesenchyme cells in the mid-suture region that upregulate a suite of genes including BMP antagonists (e.g. grem1a) and pro-angiogenic factors. Lineage tracing with grem1a:nlsEOS reveals that this mid-suture subpopulation is largely non-osteogenic. Moreover, combinatorial mutation of BMP antagonists enriched in this mid-suture subpopulation results in increased BMP signaling in the suture, misregulated bone formation, and abnormal suture morphology. These data reveal establishment of a non-osteogenic mesenchyme population in the mid-suture region that restricts bone formation through local BMP antagonism, thus ensuring proper suture morphology.

Development of the cranial lateral line system of Brook Trout, Salvelinus fontinalis (Teleostei: Salmonidae): Evolutionary and ecological implications.

The mechanosensory lateral line (LL) system of salmonid fishes has been the focus of comparative morphological studies and behavioral and physiological analyses of flow sensing capabilities, but its morphology and development have not been studied in detail in any one species. Here, we describe the post-embryonic development of the cranial LL system in Brook Trout, Salvelinus fontinalis, using vital fluorescent staining (4-Di-2-ASP), scanning electron microscopy, µCT, and clearing and staining to visualize neuromasts and the process of cranial LL canal morphogenesis. We examined the relationship between the timing of LL development, the prolonged life history of salmonids, and potential ecological implications. The LL system is composed of seven canals containing canal neuromasts (CNs) and four lines of superficial neuromasts (SNs) on the skin. CNs and SNs increase in number and size during the alevin (larval) stage. CN number stabilizes as canal morphogenesis commences, but SN number increases well into the parr (juvenile) stage. CNs become larger and more elongated than SNs, but the relative area occupied by sensory hair cells decreases during ontogeny in both types of neuromasts. Neuromast-centered canal morphogenesis starts in alevins (yolk sac larvae), as they swim up into the water column from their gravel nests (~4 months post-fertilization), after which yolk sac absorption is completed and exogenous feeding begins. Canal morphogenesis proceeds asynchronously within and among canal series and is not complete until ~8 months post-fertilization (the parr stage). Three characters in the LL system and associated dermal bones were used to identify their homologs in other actinopterygians and to consider the evolution of LL canal reduction, thus demonstrating the value of salmonids for the study of LL evolution. The prolonged life history of Brook Trout and the onset of canal morphogenesis at swim-up are predicted to have implications for neuromast function at these critical behavioral and ecological transitions.

Craniofacial studies in chicken embryos confirm the pathogenicity of human FZD2 variants associated with Robinow syndrome.

Robinow syndrome is a rare disease caused by variants of seven WNT pathway genes. Craniofacial features include widening of the nasal bridge and jaw hypoplasia. We used the chicken embryo to test whether two missense human FZD2 variants (1301G>T, p.Gly434Val; 425C>T, p.Pro142Lys) were sufficient to change frontonasal mass development. In vivo, the overexpression of retroviruses with wild-type or variant human FZD2 inhibited upper beak ossification. In primary cultures, wild-type and variant human FZD2 significantly inhibited chondrogenesis, with the 425C>T variant significantly decreasing activity of a SOX9 luciferase reporter compared to that for the wild type or 1301G>T. Both variants also increased nuclear shuttling of ß-catenin (CTNNB1) and increased the expression of TWIST1, which are inhibitory to chondrogenesis. In canonical WNT luciferase assays using frontonasal mass cells, the variants had dominant-negative effects on wild-type FZD2. In non-canonical assays, the 425C>T variant failed to activate the reporter above control levels and was unresponsive to exogenous WNT5A. This is the first single amino acid change to selectively alter ligand binding in a FZD receptor. Therefore, FZD2 missense variants are pathogenic and could lead to the altered craniofacial morphogenesis seen in Robinow syndrome.

3D atlas of the human fetal chondrocranium in the middle trimester.

The chondrocranium provides the key initial support for the fetal brain, jaws and cranial sensory organs in all vertebrates. The patterns of shaping and growth of the chondrocranium set up species-specific development of the entire craniofacial complex. The 3D development of chondrocranium have been studied primarily in animal model organisms, such as mice or zebrafish. In comparison, very little is known about the full 3D human chondrocranium, except from drawings made by anatomists many decades ago. The knowledge of human-specific aspects of chondrocranial development are essential for understanding congenital craniofacial defects and human evolution. Here advanced microCT scanning was used that includes contrast enhancement to generate the first 3D atlas of the human fetal chondrocranium during the middle trimester (13 to 19 weeks). In addition, since cartilage and bone are both visible with the techniques used, the  endochondral ossification of cranial base was mapped since this region is so critical for brain and jaw growth. The human 3D models are published as a scientific resource for human development.

Mesenchymal Wnts are required for morphogenetic movements of calvarial osteoblasts during apical expansion.

Apical expansion of calvarial osteoblast progenitors from the cranial mesenchyme (CM) above the eye is integral to calvarial growth and enclosure of the brain. The cellular behaviors and signals underlying the morphogenetic process of calvarial expansion are unknown. Time-lapse light-sheet imaging of mouse embryos revealed calvarial progenitors intercalate in 3D in the CM above the eye, and exhibit protrusive and crawling activity more apically. CM cells express non-canonical Wnt/planar cell polarity (PCP) core components and calvarial osteoblasts are bidirectionally polarized. We found non-canonical ligand Wnt5a-/- mutants have less dynamic cell rearrangements and protrusive activity. Loss of CM-restricted Wntless (CM-Wls), a gene required for secretion of all Wnt ligands, led to diminished apical expansion of Osx+ calvarial osteoblasts in the frontal bone primordia in a non-cell autonomous manner without perturbing proliferation or survival. Calvarial osteoblast polarization, progressive cell elongation and enrichment for actin along the baso-apical axis were dependent on CM-Wnts. Thus, CM-Wnts regulate cellular behaviors during calvarial morphogenesis for efficient apical expansion of calvarial osteoblasts. These findings also offer potential insights into the etiologies of calvarial dysplasias.

Perinatal imaging findings of a fetus with Pfeiffer syndrome and a heterozygous c.1019A>G, p.Tyr340Cys (Y340C) mutation in FGFR2 presenting a cloverleaf skull, craniosynostosis and short limbs on prenatal ultrasound mimicking thanatophoric dysplasia type II.

OBJECTIVE: We present perinatal imaging findings of a fetus with Pfeiffer syndrome and a heterozygous c.1019A>G, p.Tyr340Cys (Y340C) mutation in FGFR2 presenting a cloverleaf skull, craniosynostosis and short limbs on prenatal ultrasound mimicking thanatophoric dysplasia type II (TD2). CASE REPORT: A 37-year-old, gravida 2, para 1, woman underwent amniocentesis at 17 weeks of gestation because of advanced maternal age. Amniocentesis revealed a karyotype of 46,XY. However, craniofacial anomaly was found on prenatal ultrasound at 21 weeks of gestation, which showed a cloverleaf skull with severe craniosynostosis and relatively short straight long bones. Fetal magnetic resonance imaging (MRI) analysis at 22 weeks of gestation showed a cloverleaf skull, proptosis and relatively shallowing of the sylvian fissures. Prenatal ultrasound at 24 weeks of gestation showed a fetus with a cloverleaf skull with a biparietal diameter (BPD) of 6.16 cm (equivalent to 24 weeks), an abdominal circumference (AC) of 18.89 cm (equivalent to 24 weeks) and a femur length (FL) of 3.65 cm (equivalent to 21 weeks). A tentative diagnosis of TD2 was made. The pregnancy was subsequently terminated, and a 928-g malformed fetus was delivered with severe craniosynostosis, proptosis, midface retrusion, a cloverleaf skull, broad thumbs and broad big toes. The broad thumbs were medially deviated. Whole body X-ray showed a cloverleaf skull and straight long bones. However, molecular analysis of FGFR3 on the fetus revealed no mutation in the target regions. Subsequent whole exome sequencing (WES) on the DNA extracted from umbilical cord revealed a heterozygous c.1019A>G, p.Tyr340Cys (Y340C) mutation in the FGFR2 gene. CONCLUSION: Fetuses with a Y340C mutation in FGFR2 may present a cloverleaf skull on prenatal ultrasound, and WES is useful for a rapid differential diagnosis of Pfeiffer syndrome from TD2 under such a circumstance.

Key Roles of Gli1 and Ihh Signaling in Craniofacial Development.

The Hedgehog (Hh) signaling pathway orchestrates its influence through a dynamic interplay of Hh proteins, the cell surface receptor Ptch1, Smo, and Gli transcription factors, contributing to a myriad of developmental events. Indian Hedgehog (Ihh) and Gli zinc finger transcription factor 1 (Gli1) play crucial roles in developmental regulation within the Hh signaling pathway. Ihh regulates chondrocyte proliferation, differentiation, and bone formation, impacting the development of cranial bones, cartilage, and the temporomandibular joint (TMJ). Losing Ihh results in cranial bone malformation and decreased ossification and affects the formation of cranial base cartilage unions, TMJ condyles, and joint discs. Gli1 is predominantly expressed during early craniofacial development, and Gli1+ cells are identified as the primary mesenchymal stem cells (MSCs) for craniofacial bones, crucial for cell differentiation and morphogenesis. In addition, a complex mutual regulatory mechanism exists between Gli1 and Ihh, ensuring the normal function of the Hh signaling pathway by directly or indirectly regulating each other's expression levels. And the interaction between Ihh and Gli1 significantly impacts the normal development of craniofacial tissues. This review summarizes the pivotal roles of Gli1 and Ihh in the intricate landscape of mammalian craniofacial development and outlines the molecular regulatory mechanisms and intricate interactions governing the growth of bone and cartilage exhibited by Gli1 and Ihh, which provides new insights into potential therapeutic strategies for related diseases or researches of tissue regeneration.

Early embryogenesis in CHDFIDD mouse model reveals facial clefts and altered cranial neurogenesis.

CDK13-related disorder, also known as congenital heart defects, dysmorphic facial features and intellectual developmental disorder (CHDFIDD) is associated with mutations in the CDK13 gene encoding transcription-regulating cyclin-dependent kinase 13 (CDK13). Here, we focused on the development of craniofacial structures and analyzed early embryonic stages in CHDFIDD mouse models, with one model comprising a hypomorphic mutation in Cdk13 and exhibiting cleft lip/palate, and another model comprising knockout of Cdk13, featuring a stronger phenotype including midfacial cleft. Cdk13 was found to be physiologically expressed at high levels in the mouse embryonic craniofacial structures, namely in the forebrain, nasal epithelium and maxillary mesenchyme. We also uncovered that Cdk13 deficiency leads to development of hypoplastic branches of the trigeminal nerve including the maxillary branch. Additionally, we detected significant changes in the expression levels of genes involved in neurogenesis (Ache, Dcx, Mef2c, Neurog1, Ntn1, Pou4f1) within the developing palatal shelves. These results, together with changes in the expression pattern of other key face-specific genes (Fgf8, Foxd1, Msx1, Meis2 and Shh) at early stages in Cdk13 mutant embryos, demonstrate a key role of CDK13 in the regulation of craniofacial morphogenesis.

Metopismo: bases morfológicas, implicancias clínicas y reporte de caso / Metopism: morphologic basis clinical implications and case report

Durante la vida fetal y la infancia, los huesos planos de la bóveda craneal están separados por membranas densas de tejido conectivo que constituyen articulaciones fibrosas conocidas como suturas; las cuales tienen como objetivo durante los primeros estadios de la vida favorecer el desarrollo encefálico. Eventualmente estas suturas con el paso de los años se cierran formando una sinostosis entre los huesos del cráneo. Una de estas es la sutura frontal, que une los 2 huesos frontales en la época embrionaria y en el recién nacido. Esta sutura puede persistir en el tiempo generando el cuadro conocido como metopismo. Alteración que muestra distintas presentaciones e incidencias según sea el grupo étnico estudiado. El propósito de este artículo es mostrar las características que presenta esta condición, frecuencias, descripciones, variedades, etc., analizando distintas bases de datos, junto a la descripción de un caso. Se plantea la importancia que posee a nivel clínico a la hora de invadir quirúrgicamente esa zona, o la confusión que se puede presentar a nivel radiográfico lo cual eventualmente puede generar alguna complicación, por lo cual es de real relevancia el conocimiento de las bases morfológicas de esta condición con el fin de realizar un correcto diagnóstico y procedimiento quirúrgico si este lo amerita.

During fetal life and infancy, flat bones of the cranial vault are separated by dense connective tissue membranes, fibrous joints called sutures, which are aimed early on in life to promote brain development. Eventually these sutures close over the years to form a synostosis between the bones of the skull. One of these is the frontal suture, which joins the two frontal bones in the embryonic period and the newborn. This suture may persist over time, generating the condition known as metopism. Alteration showing different presentations and incidents depending on the ethnic group studied. The purpose of this paper is to show the features found in this condition, frequency, description, varieties, etc. This analysis was performed on different databases and the description of a case. It raises the importance that clinicians approaching the area at the time of surgery consider possible confusion at the radiographic level which can lead to subsequent complications. Therefore, real knowledge of the morphological bases of this condition is important for correct diagnosis and surgical procedure if warranted.

Frecuencia de hueso lambdoideo en cráneos con deformación artificial en el norte de Chile / Frecuency of wormian lambdoid bone in skulls with artificial deformation in Northern Chile

Los huesos suturales o wormianos son huesos accesorios, de importancia genética y hereditaria, considerados variables étnicas (Orts Llorca, 1958; Figún & Garino, 1992). Se caracterizan por ser diversos en número, tamaño y forma, ubicados en suturas y fontículos, de preferencia en suturas posteriores, predominando la frecuencia a nivel de sutura lambdoidea o parieto-occipital (Sappey 1888, Sicher, 1965; Sánchez-Lara et al., 2004). Son de interés para la anatomía humana, antropología física, imagenología y medicina legal (Lips & García-Hernández, 1983; Henríquez-Pino et al., 1992; Braga et al., 2000; García-Hernández et al., 2007). La deformación craneal, patológica o artificial, estimula la formación de centros accidentales de osificación, incrementando la presencia de osículos en suturas y fontículos (Del Papa & Pérez, 2007). La deformación craneal artificial era común en diversas culturas amerindias, con propósito estético, mágico, religioso, como forma de identificación étnica, social, nobleza o asociada al grupo gobernante (Torres-Rouff, 2007) y se realizaba aplicando tablas de madera o vendajes compresivos en la cabeza del recién nacido. La hipótesis de investigación es determinar si existe mayor número de osículos lambdoideos en cráneos de atacameños del norte de Chile con y sin deformación craneal artificial. Para cumplir este objetivo se estudiaron 77 cráneos atacameños de ambos sexos (27 deformados y 50 no deformados), seleccionados al azar entre 293 individuos exhumados del cementerio Coyo-Oriente, datados entre 300-1200 D.C. y que forman parte del Museo R.P. Gustavo Le Paige en San Pedro de Atacama de la Universidad Católica del Norte. Los cráneos fueron analizados, fotografiados y mensurados para determinar el índice craneano. Existe prevalencia de huesos lambdoideos en cráneos deformados (p<0,05=0,00000249247), con promedio de indice craneal con mayor hiperbraquicefalia (92,63 DS 9,72) y porcentaje de cráneos braquicefálicos con huesos...

Sutural or wormians bones are accesory bones, with genetic and heriditary importance, and consided ethnic variables (Orts Llorca, 1958; Figún & Garino, 1992). They are characterized by be variables in number, size and shape, located in sutures and fontanelles, preferably in posteriorly placed sutures (Sappey 1888, Sicher, 1965; Sánchez-Lara et al., 2007). They are of interest in human anatomy, physical anthropology, imagenology and legal medicine (Lips & García-Hernández, 1983; Henríquez-Pino et al., 1992; Braga et al., 2000; García-Hernández et al., 2007). Cranial deformation, pathological or artificial, stimulates the formation of accidental ossification centers, increasing the formation of ossicles in sutures and fontanelles (Del Papa & Pérez, 2007). Artificial cranial deformation was common in amerindian cultures, for aesthetic, magical or religious purpose, as a form of ethnic identificate, social, nobility or associated with the ruling group (Torres-Rouff, 2007) and it was performed applying wooden boards or bandages in the head of newborn. The hypothesis of investigation is to determinate if there is a greater number of ossicles lambdoid in skulls of atacameños in Northern Chile with and without artificial cranial deformation. To fulfill this goal we studied 77 atacameños skulls of both sexes (27 deformed y 50 not deformed), selected at random between 293 individuals of the Coyo-Orient cementery, dated between 300-1200 A.C. and these remains are part of the Museum R.P. Gustavo Le Paige in San Pedro de Atacama of the North Catholic University. All skulls were analyzed, photographed in all anatomical norms and measured to obtain the cranial index. There prevalence of lambdoid bones in artificial cranial deformed (p<0,05=0,00000249247), with average cranial index with greater hyperbrachycephaly (92,63 DS 9,72) and greater percentage of brachycephalic skulls with lambdoid bones (92,6 percent-32 percent; p<0,05=3,67073E-7).

Estudio morfométrico del foramen parietal / Morphometry study of the parietal foramen

Los huesos parietales habitualmente presentan pequeños forámenes, estos en número de dos se encuentran situados próximo de la unión de la sutura sagital con la lambdoidea. Éstos forámenes permiten que venas emisarias drenen en el seno longitudinal superior a venas occipitales y, algunas veces, transmite una pequeña rama de la arteria occipital. Se efectuó un estudio anatómico en 39 calotas, en buen estado de conservación, de individuos adultos, del museo de la Unidad de Anatomía, Universidad de La Frontera, Chile. Se registraron los siguientes datos: presencia del foramen parietal, distancia desde el lambda al foramen parietal y desde el foramen parietal a la sutura sagital, diámetro del foramen parietal. El 58,9% de las calotas presentaban cada uno de los huesos parietales un foramen; el 25,6% presentaba un foramen en un parietal no existiendo en el hueso contralateral; y el 15,3% no presentaba foramen parietal. La distancia promedio del lambda al foramen parietal fue de 33,25 mm; la distancia de la sutura sagital al foramen parietal fue en promedio de 6,29mm; el promedio del diámetro máximo del foramen parietal fue de 2,65mm y el mínimo de 0,37mm. Estos datos anatómicos del foramen parietal aportan nuevos antecedentes para futuros estudios.

The bone parietal foramina usually minor, in these two numbers are located near the junction of the sagittal suture with lambdoidea. These foramina allow emissary veins draining into the superior longitudinal sinus in the occipital veins, and sometimes sends a small branch of the occipital artery. Anatomical studies in 39 cranium, well-preserved, adult, of the Anatomy Museum of the Universidad de La Frontera, Chile was realized. Recorded the following data: presence of the parietal foramen, the distance from the lambda and the parietal foramen parietal foramen to the sagittal suture and diameter of the parietal foramen. The 58.9% of the cranium presented each of the parietal bone foramen, 25.6% had a parietal foramen in a bone in the absence of contralateral and 15.3% had no parietal foramen. The average distance from lambda to parietal foramen was 33.25 mm, the distance from the sagittal suture to the parietal foramen averaged 6.29 mm, the average maximum diameter of the parietal foramen was 2.65 mm and a minimum of 0 , 37mm. These anatomical data provide new parietal foramen of the background for future studies.

Estudos moleculares em anomalias craniofaciais raras: sindrome blefaroqueilodontica e efeitos de linha media facial com hipertelorismo / Molecular biological studies in rare craniofacial anomalies

A Síndrome Blefaroqueilodôntica (BCD) e os Defeitos de Linha Média Facial com Hipertelorismo (DLMFH) são defeitos craniofaciais raros. Por esse motivo, os estudos de grandes casuísticas têm sido limitados. Contribuição científica significativa neste assunto tem sido dada por nosso grupo, que delineou características clínicas e diretrizes para seguimento de longo prazo e evidenciou achados neuroradiológicos em ambas as anomalias. Embasado nesses achados preliminares e evidências recentes da literatura pertinente, foi possível estabelecer uma estratégia inicial para investigação etiológica da BCD e dos DLMFH, sendo os objetivos desse projeto: investigar a etiologia da BCD nos indivíduos afetados pela síndrome, por meio de estudo dos genes candidatos IRF6, P63, OSR2, TBX10, FOXE1, SHH, FGF8 e PAX3; pesquisar, nos indivíduos com DLMFH, a presença de mutações nos genes candidatos SHH, FGF8 e PAX3; identificar, em ambas as malformações, possíveis alterações cromossômicas; e, por último, associar os achados clínicos detectados nas investigações anteriores aos possíveis achados moleculares. Foram utilizadas técnicas de sequenciamento direto, array-CGH, genotipagem automática e hibridação in situ por fluorescência. Não foi possível relacionar nenhuma mutação pontual nos genes estudados associadas às malformações em questão, pois não foram encontradas alterações gênicas patogênicas. Entretanto foram detectadas em pacientes com DLFMH três aberrações cromossômicas em regiões distintas do genoma, tratando-se de um caso de duplicação no cromossomo...

The Blepharocheilodontic Syndrome (BCD) and Midline Facial Defects with Ocular Hypertelorism (MFDH) are rare craniofacial anomalies. Considering the rarity of these two groups of congenital defects, studies with large casuistry have been limited. Our group has significantly contributed to the scientific knowledge about both anomalies, delineating clinical characteristics, evidencing neurological findings and designing protocols for long term follow-up. Based in these preliminary findings and recent evidences of pertinent literature, it was possible to determine an initial etiologic investigation strategy for the BCD and the MFDH. The objectives of this project are to investigate the etiology of the BCD in affected individuals through IRF6, P63, OSR2, TBX10, FOXE1, SHH, FGF8 and PAX3 candidate genes study; to search MFDH patients for mutations in the SHH, FGF8 and PAX3 candidate genes; to identify, in both syndromes...

Frecuencia del hueso interparietal o incaico en cráneos atácamenos (Lican antai) prehispánicos del norte de Chile / Frequency of interparietal bone or inca bone in pre-hispanic Atacamenos (Lican Antai) skulls of the north of Chile

El hueso interparietal se considera un hueso intercalar originado de centros independientes de osificación y rodeado por sus propias suturas. Se encontró en fósiles homínidos y humanos tempranos. Se cree que el occipucio sufre transformaciones por mutaciones al iniciarse la evolución humana reforzando esta teoría las variaciones suturales que presenta el occipital. Sería un rasgo genéticamente dominante, propuesta ratificada por estudios experimentales. Se observa con variadas formas según la fusión de los núcleos de osificación, por lo que todos los huesos ubicados en la zona de la escama del occipital no se pueden clasificar como suturales o wormianos y deben considerarse como parte del hueso interparietal. Tratando de confirmar la alta frecuencia obtenida en investigaciones anteriores realizadas en cráneos de individuos originarios del norte de Chile, se analizaron 83 cráneos de atacamenos prehispánicos de ambos sexos, seleccionados al azar entre 293 individuos exhumados del cementerio Coyo-Oriente, datados entre 300-1200 D.C período post-Tiwanaku y que forman parte del Museo R.P. Gustavo Le Paige en San Pedro de Atacama, dependiente del Instituto de Investigaciones Arqueológicas de la Universidad Católica del Norte, que fueron fotografiados en todas sus normas anatómicas y que se midieron paras obtener el índice craneal o cefálico. El hueso interparietal está presente en 23 de 83 cráneos, con una frecuencia de 27,71 por ciento, sin diferencias estadísticas significativas al 95 por ciento con investigaciones realizadas en cráneos de origen étnico similar y en otras etnias que presentan alta frecuencia de hueso interparietal. Por el contrario, se encontraron diferencias estadísticamente significativas al 95 por ciento con frecuencias determinadas en cráneos europeos caucásicos y euroasiáticos. Los autores integraron las tablas clasificatorias de Kadanoff y Hanihara-Ishida, para obtener una tabla modificada que permitiera clasificar ...

The interparietal bone is considered an intercalary bone originated by independent ossification centers and surrounded by its own sutures. It is found in early hominids and human fossils. It is believed that the occipital bone undergoes transformations by mutations at the beginning of human evolution. Reinforcing this theory are the suture variations that presents the occipital bone. It would be a dominant genetic characteristic, proposal ratified by experimental studies. It is observed with varied forms according to the fusion of the ossification nuclei; reason why all the bones located in the zone of the occipital flake cannot be classified as sutures or wormians and must be considered part of the interparietal bone. Trying to confirm the high frequency obtained in previous investigations realized in skulls of original individuals of the north of Chile, we analyzed 83 skulls of pre-Hispanic atácamenos (lican antai) of both sexes, selected at random between 293 individuals of the Coyo-Orient cementery, dated between 300-1200 A.C, post-Tiwanaku period and these remains are part of R.P Gustavo Le Paige's Museum in San Pedro de Atacama, which is part of the Institute of Archaeological Investigations of the North Catholic University. The remains were photographed in all anatomical norms and that were measured to obtain the cranial or cephalic Index. The interparietal bone is present in 23 of 83 skulls, with a frequency of 27.71 percent, without significant statistical differences to 95 percent with investigations realized in skulls of similar ethnic origin and other ethnic groups who present high frequency of interparietal bone. On the contrary, statistically significant differences to 95 percent were found with frequencies determined in caucasian and euroasiatics european skulls. The authors integrated the classificatory tables of Kadanoff and Hanihara-Ishida, to obtain a modified table that allowed to classify all the found variations ...

Avaliação do potencial osteogênico de matrizes tridimensionais colagênicas aniônicas, reticuladas ou não em glutaraldeído, na regeneração de defeitos críticos, em calvária de rato / Evaluation of the osteogenic potential of three-dimensional arrays collagenic anionic, crosslinked or not in glutaraldehyde, the regeneration of critical defects in rat calvaria

O objetivo deste trabalho foi avaliar histomorfometricamente, por microscopia de luz comum, o potencial osteogênico de matrizes colagênicas aniônicas, reticuladas ou não em glutaraldeído, implantadas em defeitos ósseos críticos, em calvária de ratos. Foram utilizados 86 ratos divididos aleatoriamente para compor quatro grupos: GI - matriz colagênica aniônica com 24h de hidrólise e 15min de reticulação em GA 0,05 por cento (MCAHGA); GII - matriz colagênica aniônica com 24h de hidrólise (MCA); GIII - matriz colagênica neutra, controle positivo (MCN) e GIV - defeito ósseo vazio, sem implantação de biomaterial, preenchido por coágulo sanguíneo, controle negativo. Os animais foram avaliados nos pontos biológicos de 15, 45, 90 e 120 dias. Os resultados evidenciaram que os biomateriais implantados nos grupos I e II foram biocompatíveis, embora tenham desencadeado inflamação crônica granulomatosa discreta e regressiva. Estas matrizes apresentaram velocidade de biodegradação compatível com a neoformação óssea, a qual se mostrou associada a angiogênese no interior das matrizes, em todos os pontos biológicos. No GIII, a fragmentação e biodegradação mostraram-se acentuadas, pela ausência de tratamento químico do colágeno. A neomineralização evidenciada nos grupos I e II apresentou aumento estatisticamente significante ao longo dos tempos. O percentual de mineralização do Gil (87 por cento) foi estatisticamente diferente daquele encontrado no GI (66 por cento). Ao compararmos estes percentuais com a mineralização observada no GIV, notam-se diferenças muito significantes. Neste último, assim como no GIII, a neoformação óssea esteve limitada às bordas do defeito com fibrose na área seccional do defeito. Conclui-se que as matrizes colagênicas aniônicas apresentaram potencial osteogênico mais evidente nas matrizes sem reticulação em glutaraldeído. Estas matrizes apresentam grande potencial de aplicabilidade clínica, nas terapias regenerativas ósseas.

Histological examination of major craniofacial abnormalities produced in rat foetuses with a variety of retinoids

Retinoic acid is a vitamin-A derived compoundthat plays an important role in craniofacialdevelopment. However, numerousstudies have shown that exogenously administeredretinoic acid analogues have teratogeniceffects both in humans and in experimentalanimals. This paper presents the results of astudy where exogenous administration ofretinoic acid analogues to pregnant Wistarrats resulted in major craniofacial malformationsof most of the foetuses. Seven groups ofpregnant rats were exposed to a variety ofretinoic acid analogues, administered in differentdoses on different gestational days. Afurther control group was not exposed to thesecompounds. All the rats were impregnatedand sacrificed on the same gestational days(GD 0 and GD 18 respectively). Followingexamination of the 34 foetuses obtained fromthe retinoic acid-treated litters, 5 were chosenfor histological investigation to describe themajor, external craniofacial malformationsresulting from exposure to the teratogens.These malformations included exophthalmos,anophthalmos, exencephaly, craniofacial asymmetryand facial tags. Also reported here arethe incidences of teratomas and absorptions inthese litters. Previously, we have reported theincidence of cleft lip and palate in rats subjectedto an identical experimental regimen. Ourdata provide further evidence that retinoicacid analogues, all-trans-retinoic acid in particular,disturb normal craniofacial developmentin such a way that a spectrum ofcraniofacial malformations can be induced byembryonic exposure to these compounds (AU)

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Neuroanatomía

Un texto completo, excelentemente ilustrado sobre el tema: Organización general, estructura y origen del sistema nervioso. El sistema nervioso central y sus envolturas:cráneo y raquis. Médula espinal. Tronco encefálico. Cerebelo. Desarrollo del cerebro. Diencéfalo. Hemisferios cerebrales. Corteza cerebral. Circulación encefálica. Topografía craneoencefálica. El sistema nervioso periferico. Organización anatomo-funcional del sistema nervioso

Neuroanatomía

Un texto completo, excelentemente ilustrado sobre el tema: Organización general, estructura y origen del sistema nervioso. El sistema nervioso central y sus envolturas:cráneo y raquis. Médula espinal. Tronco encefálico. Cerebelo. Desarrollo del cerebro. Diencéfalo. Hemisferios cerebrales. Corteza cerebral. Circulación encefálica. Topografía craneoencefálica. El sistema nervioso periferico. Organización anatomo-funcional del sistema nervioso