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1.
Development ; 147(4)2020 02 17.
Artigo em Inglês | MEDLINE | ID: mdl-31988190

RESUMO

Epibranchial placodes are the geniculate, petrosal and nodose placodes that generate parts of cranial nerves VII, IX and X, respectively. How the three spatially separated placodes are derived from the common posterior placodal area is poorly understood. Here, we reveal that the broad posterior placode area is first patterned into a Vgll2+/Irx5+ rostral domain and a Sox2+/Fgf3+/Etv5+ caudal domain relative to the first pharyngeal cleft. This initial rostral and caudal patterning is then sequentially repeated along each pharyngeal cleft for each epibranchial placode. The caudal domains give rise to the neuronal and non-neuronal cells in the placode, whereas the rostral domains are previously unrecognized structures, serving as spacers between the final placodes. Notch signalling regulates the balance between the rostral and caudal domains: high levels of Notch signalling expand the caudal domain at the expense of the rostral domain, whereas loss of Notch signalling produces the converse phenotype. Collectively, these data unravel a new patterning principle for the early phases of epibranchial placode development and a role for Notch signalling in orchestrating epibranchial placode segregation and differentiation.


Assuntos
Região Branquial/embriologia , Nervos Cranianos/embriologia , Ectoderma/embriologia , Receptores Notch/fisiologia , Animais , Padronização Corporal , Diferenciação Celular , Linhagem da Célula , Feminino , Perfilação da Expressão Gênica , Regulação da Expressão Gênica no Desenvolvimento , Genótipo , Camundongos , Camundongos Endogâmicos C57BL , Neurônios/citologia , Fenótipo , Domínios Proteicos , Transdução de Sinais , Fatores de Tempo , Fatores de Transcrição/genética
2.
Genesis ; 57(1): e23282, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30628162

RESUMO

Organs and structures of the vertebrate head perform a plethora of tasks including visualization, digestion, vocalization/communication, auditory functions, and respiration in response to neuronal input. This input is primarily derived from afferent and efferent fibers of the cranial nerves (sensory and motor respectively) and efferent fibers of the cervical sympathetic trunk. Despite their essential contribution to the function and integration of processes necessary for survival, how organ innervation is established remains poorly understood. Furthermore, while it has been appreciated for some time that innervation of organs by cranial nerves is regulated in part by secreted factors and cell surface ligands expressed by those organs, whether nerves also regulate the development of facial organs is only beginning to be elucidated. This review will provide an overview of cranial nerve development in relation to the organs they innervate, and outline their known contributions to craniofacial development, thereby providing insight into how nerves may shape the organs they innervate during development. Throughout, the interaction between different cell and tissue types will be highlighted.


Assuntos
Nervos Cranianos/embriologia , Morfogênese , Crista Neural/embriologia , Animais , Humanos , Crânio/embriologia
3.
Semin Cell Dev Biol ; 91: 23-30, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-30385045

RESUMO

Cranial foramina are holes in the skull through which nerves and blood vessels pass to reach both deep and superficial tissues. They are often overlooked in the literature; however they are complex structures that form within the developing cranial bones during embryogenesis and then remain open throughout life, despite the bone surrounding them undergoing constant remodelling. They are invaluable in assigning phylogeny in the fossil record and their size has been used, by some, to imply function of the nerve and/or blood vessel that they contained. Despite this, there are very few studies investigating the development or normal function of the cranial foramina. In this review, we will discuss the development of the cranial foramina and their subsequent maintenance, highlighting key gaps in the knowledge. We consider whether functional interpretations can be made from fossil material given a lack of knowledge regarding their contents and maintenance. Finally, we examine the significant role of malformation of foramina in congenital diseases such as craniosynostosis.


Assuntos
Encéfalo/anatomia & histologia , Nervos Cranianos/anatomia & histologia , Crânio/anatomia & histologia , Artéria Vertebral/anatomia & histologia , Animais , Evolução Biológica , Encéfalo/embriologia , Nervos Cranianos/embriologia , Encefalocele/embriologia , Humanos , Modelos Anatômicos , Crânio/irrigação sanguínea , Crânio/embriologia , Artéria Vertebral/embriologia
4.
J Anat ; 233(2): 222-242, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29797482

RESUMO

Orofacial clefting represents the most common craniofacial birth defect. Cleft lip with or without cleft palate (CL/P) is genetically distinct from cleft palate only (CPO). Numerous transcription factors (TFs) regulate normal development of the midface, comprising the premaxilla, maxilla and palatine bones, through control of basic cellular behaviors. Within the Pbx family of genes encoding Three Amino-acid Loop Extension (TALE) homeodomain-containing TFs, we previously established that in the mouse, Pbx1 plays a preeminent role in midfacial morphogenesis, and Pbx2 and Pbx3 execute collaborative functions in domains of coexpression. We also reported that Pbx1 loss from cephalic epithelial domains, on a Pbx2- or Pbx3-deficient background, results in CL/P via disruption of a regulatory network that controls apoptosis at the seam of frontonasal and maxillary process fusion. Conversely, Pbx1 loss in cranial neural crest cell (CNCC)-derived mesenchyme on a Pbx2-deficient background results in CPO, a phenotype not yet characterized. In this study, we provide in-depth analysis of PBX1 and PBX2 protein localization from early stages of midfacial morphogenesis throughout development of the secondary palate. We further establish CNCC-specific roles of PBX TFs and describe the developmental abnormalities resulting from their loss in the murine embryonic secondary palate. Additionally, we compare and contrast the phenotypes arising from PBX1 loss in CNCC with those caused by its loss in the epithelium and show that CNCC-specific Pbx1 deletion affects only later secondary palate morphogenesis. Moreover, CNCC mutants exhibit perturbed rostro-caudal organization and broadening of the midfacial complex. Proliferation defects are pronounced in CNCC mutants at gestational day (E)12.5, suggesting altered proliferation of mutant palatal progenitor cells, consistent with roles of PBX factors in maintaining progenitor cell state. Although the craniofacial skeletal abnormalities in CNCC mutants do not result from overt patterning defects, osteogenesis is delayed, underscoring a critical role of PBX factors in CNCC morphogenesis and differentiation. Overall, the characterization of tissue-specific Pbx loss-of-function mouse models with orofacial clefting establishes these strains as unique tools to further dissect the complexities of this congenital craniofacial malformation. This study closely links PBX TALE homeodomain proteins to the variation in maxillary shape and size that occurs in pathological settings and during evolution of midfacial morphology.


Assuntos
Nervos Cranianos/embriologia , Proteínas de Homeodomínio/fisiologia , Palato/embriologia , Fator de Transcrição 1 de Leucemia de Células Pré-B/fisiologia , Proteínas Proto-Oncogênicas/fisiologia , Animais , Fissura Palatina/genética , Nervos Cranianos/metabolismo , Feminino , Camundongos , Camundongos Transgênicos , Palato/metabolismo , Gravidez
5.
Dev Biol ; 444 Suppl 1: S67-S78, 2018 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-29571614

RESUMO

The neural crest is a transient population of cells that forms within the developing central nervous system and migrates away to generate a wide range of derivatives throughout the body during vertebrate embryogenesis. These cells are of evolutionary and clinical interest, constituting a key defining trait in the evolution of vertebrates and alterations in their development are implicated in a high proportion of birth defects and craniofacial abnormalities. In the hindbrain and the adjacent cranial neural crest cells (cNCCs), nested domains of Hox gene expression provide a combinatorial'Hox-code' for specifying regional properties in the developing head. Hox genes have been shown to play important roles at multiple stages in cNCC development, including specification, migration, and differentiation. However, relatively little is known about the underlying gene-regulatory mechanisms involved, both upstream and downstream of Hox genes. Furthermore, it is still an open question as to how the genes of the neural crest GRN are linked to Hox-dependent pathways. In this review, we describe Hox gene expression, function and regulation in cNCCs with a view to integrating these genes within the emerging gene regulatory network for cNCC development. We highlight early roles for Hox1 genes in cNCC specification, proposing that this may be achieved, in part, by regulation of the balance between pluripotency and differentiation in precursor cells within the neuro-epithelium. We then describe what is known about the regulation of Hox gene expression in cNCCs and discuss this from the perspective of early vertebrate evolution.


Assuntos
Genes Homeobox/fisiologia , Cabeça/embriologia , Crista Neural/metabolismo , Animais , Evolução Biológica , Padronização Corporal/fisiologia , Diferenciação Celular , Movimento Celular , Sistema Nervoso Central/embriologia , Sequência Conservada , Nervos Cranianos/embriologia , Regulação da Expressão Gênica no Desenvolvimento/genética , Redes Reguladoras de Genes/genética , Genes Homeobox/genética , Humanos , Crista Neural/citologia , Crista Neural/embriologia , Tubo Neural , Neurônios , Rombencéfalo/metabolismo , Crânio , Vertebrados/embriologia , Vertebrados/genética
6.
J Anat ; 232(3): 431-439, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29235648

RESUMO

There is growing evidence of a direct influence of vasculature on the development of neurons in the brain. The development of the cranial vasculature has been well described in zebrafish but its anatomical relationship with the adjacent developing sensory ganglia has not been addressed. Here, by 3D imaging of fluorescently labelled blood vessels and sensory ganglia, we describe for the first time the spatial organization of the cranial vasculature in relation to the cranial ganglia during zebrafish development. We show that from 24 h post-fertilization (hpf) onwards, the statoacoustic ganglion (SAG) develops in direct contact with two main blood vessels, the primordial hindbrain channel and the lateral dorsal aortae (LDA). At 48 hpf, the LDA is displaced medially, losing direct contact with the SAG. The relationship of the other cranial ganglia with the vasculature is evident for the medial lateral line ganglion and for the vagal ganglia that grow along the primary head sinus (PHS). We also observed that the innervation of the anterior macula runs over the PHS vessel. Our spatiotemporal anatomical map of the cranial ganglia and the head vasculature indicates physical interactions between both systems and suggests a possible functional interaction during development.


Assuntos
Vasos Sanguíneos/embriologia , Encéfalo/irrigação sanguínea , Encéfalo/embriologia , Nervos Cranianos/irrigação sanguínea , Peixe-Zebra/embriologia , Animais , Nervos Cranianos/embriologia , Gânglios/irrigação sanguínea , Gânglios/embriologia
7.
Int J Dev Biol ; 61(8-9): 495-503, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29139535

RESUMO

The mammalian skull vault is a highly regulated structure that evolutionally protects brain growth during vertebrate development. It consists of several membrane bones with different tissue origins (e.g. neural crest-derived frontal bone and mesoderm-derived parietal bone). Although membrane bones are formed through intramembranous ossification, the neural crest-derived frontal bone has superior capabilities for osteoblast activities and bone regeneration via TGF, BMP, Wnt, and FGF signaling pathways. Neural crest (NC) cells are multipotent, and once induced, will follow specific paths to migrate to different locations of the body where they give rise to a diverse array of cell types and tissues. Recent studies using genetic mouse models have greatly advanced our knowledge of NC cell induction, proliferation, migration and differentiation. Perturbations or disruptions of neural crest patterning lead to severe developmental defects or diseases. This review summarizes recent discoveries including novel functions of genes or signaling molecules that are capable of governing developmental processes of neural crest patterning, which may function as a gene regulatory network in controlling skull development. The proposed regulatory network will be important to understand how the signaling pathways and genes converge to regulate osteoblast activities and bone formation, which will be beneficial for the potential identification of molecular targets to prevent or alleviate human diseases or disorders involving defective neural crest development.


Assuntos
Nervos Cranianos/embriologia , Regulação da Expressão Gênica no Desenvolvimento , Crista Neural/embriologia , Crânio/embriologia , Animais , Nervos Cranianos/fisiologia , Camundongos , Crista Neural/fisiologia , Transdução de Sinais , Crânio/fisiologia
8.
Dev Biol ; 415(2): 228-241, 2016 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-26988119

RESUMO

We compared apparent origins, cellular diversity and regulation of initial axon growth for differentiating cranial sensory neurons. We assessed the molecular and cellular composition of the developing olfactory and otic placodes, and cranial sensory ganglia to evaluate contributions of ectodermal placode versus neural crest at each site. Special sensory neuron populations-the olfactory and otic placodes, as well as those in vestibulo-acoustic ganglion- are entirely populated with cells expressing cranial placode-associated, rather than neural crest-associated markers. The remaining cranial sensory ganglia are a mosaic of cells that express placode-associated as well as neural crest-associated markers. We found two distinct populations of neural crest in the cranial ganglia: the first, as expected, is labeled by Wnt1:Cre mediated recombination. The second is not labeled by Wnt1:Cre recombination, and expresses both Sox10 and FoxD3. These populations-Wnt1:Cre recombined, and Sox10/Foxd3-expressing- are proliferatively distinct from one another. Together, the two neural crest-associated populations are substantially more proliferative than their placode-associated counterparts. Nevertheless, the apparently placode- and neural crest-associated populations are similarly sensitive to altered signaling that compromises cranial morphogenesis and differentiation. Acute disruption of either Fibroblast growth factor (Fgf) or Retinoic acid (RA) signaling alters axon growth and cell death, but does not preferentially target any of the three distinct populations. Apparently, mosaic derivation and diversity of precursors and early differentiating neurons, modulated uniformly by local signals, supports early cranial sensory neuron differentiation and growth.


Assuntos
Nervos Cranianos/citologia , Células Receptoras Sensoriais/citologia , Animais , Apoptose , Axônios/fisiologia , Diferenciação Celular , Linhagem da Célula , Nervos Cranianos/embriologia , Ectoderma/citologia , Fatores de Crescimento de Fibroblastos/fisiologia , Gânglios Sensitivos/citologia , Regulação da Expressão Gênica no Desenvolvimento/fisiologia , Proteínas Luminescentes/análise , Proteínas Luminescentes/genética , Camundongos , Camundongos Endogâmicos C57BL , Crista Neural/citologia , Neurogênese , Fatores de Transcrição/genética , Tretinoína/fisiologia , Proteína Wnt1/fisiologia
9.
Neural Dev ; 11: 3, 2016 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-26819088

RESUMO

BACKGROUND: The cranial sensory ganglia represent populations of neurons with distinct functions, or sensory modalities. The production of individual ganglia from distinct neurogenic placodes with different developmental pathways provides a powerful model to investigate the acquisition of specific sensory modalities. To date there is a limited range of gene markers available to examine the molecular pathways underlying this process. RESULTS: Transcriptional profiles were generated for populations of differentiated neurons purified from distinct cranial sensory ganglia using microdissection in embryonic chicken followed by FAC-sorting and RNAseq. Whole transcriptome analysis confirmed the division into somato- versus viscerosensory neurons, with additional evidence for subdivision of the somatic class into general and special somatosensory neurons. Cross-comparison of distinct ganglia transcriptomes identified a total of 134 markers, 113 of which are novel, which can be used to distinguish trigeminal, vestibulo-acoustic and epibranchial neuronal populations. In situ hybridisation analysis provided validation for 20/26 tested markers, and showed related expression in the target region of the hindbrain in many cases. CONCLUSIONS: One hundred thirty-four high-confidence markers have been identified for placode-derived cranial sensory ganglia which can now be used to address the acquisition of specific cranial sensory modalities.


Assuntos
Nervos Cranianos/embriologia , Nervos Cranianos/metabolismo , Gânglios Sensitivos/embriologia , Gânglios Sensitivos/metabolismo , Neurônios/fisiologia , Transcriptoma , Animais , Diferenciação Celular , Embrião de Galinha , Neurônios/metabolismo
10.
J Comp Neurol ; 524(5): 1033-61, 2016 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-26356988

RESUMO

During development, transcription factor combinatorial codes define a large variety of morphologically and physiologically distinct neurons. Such a combinatorial code has been proposed for the differentiation of projection neurons of the somatic and visceral components of cranial nerves. It is possible that individual neuronal cell types are not specified by unique transcription factors but rather emerge through the intersection of their expression domains. Brn3a, Brn3b, and Brn3c, in combination with each other and/or transcription factors of other families, can define subgroups of retinal ganglion cells (RGC), spiral and vestibular ganglia, inner ear and vestibular hair cell neurons in the vestibuloacoustic system, and groups of somatosensory neurons in the dorsal root ganglia. The present study investigates the expression and potential role of the Brn3b transcription factor in cranial nerves and associated nuclei of the brainstem. We report the dynamic expression of Brn3b in the somatosensory component of cranial nerves II, V, VII, and VIII and visceromotor nuclei of nerves VII, IX, and X as well as other brainstem nuclei during different stages of development into adult stage. We find that genetically identified Brn3b(KO) RGC axons show correct but delayed pathfinding during the early stages of embryonic development. However, loss of Brn3b does not affect the anatomy of the other cranial nerves normally expressing this transcription factor.


Assuntos
Nervos Cranianos/embriologia , Nervos Cranianos/metabolismo , Regulação da Expressão Gênica no Desenvolvimento , Proteínas de Homeodomínio/biossíntese , Proteínas de Homeodomínio/genética , Fator de Transcrição Brn-3B/biossíntese , Fator de Transcrição Brn-3B/genética , Animais , Nervos Cranianos/crescimento & desenvolvimento , Feminino , Técnicas de Introdução de Genes , Camundongos , Camundongos Transgênicos , Gravidez
11.
Anat Sci Int ; 91(3): 246-9, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-26205322

RESUMO

Morphometric measurements of cranial nerves in posterior cranial fossa of fetus cadavers were carried out in an attempt to identify any asymmetry in their openings into the cranium. Twenty-two fetus cadavers (8 females, 14 males) with gestational age ranging between 22 and 38 weeks (mean 30 weeks) were included in this study. The calvaria were removed, the brains were lifted, and the cranial nerves were identified. The distance of each cranial nerve opening to midline and the distances between different cranial nerve openings were measured on the left and right side and compared. The mean clivus length and width were 21.2 ± 4.4 and 13.2 ± 1.5 mm, respectively. The distance of the twelfth cranial nerve opening from midline was shorter on the right side when compared with the left side (6.6 ± 1.1 versus 7.1 ± 0.8 mm, p = 0.038). Openings of other cranial nerves did not show such asymmetry with regard to their distance from midline, and the distances between different cranial nerves were similar on the left and right side. Cranial nerves at petroclival region seem to show minimal asymmetry in fetuses.


Assuntos
Fossa Craniana Posterior/inervação , Nervos Cranianos/anatomia & histologia , Nervos Cranianos/embriologia , Feto/anatomia & histologia , Feto/inervação , Cadáver , Feminino , Idade Gestacional , Humanos , Masculino
12.
BMC Dev Biol ; 15: 40, 2015 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-26545946

RESUMO

BACKGROUND: TALE-class homeodomain transcription factors Meis and Pbx play important roles in formation of the embryonic brain, eye, heart, cartilage or hematopoiesis. Loss-of-function studies of Pbx1, 2 and 3 and Meis1 documented specific functions in embryogenesis, however, functional studies of Meis2 in mouse are still missing. We have generated a conditional allele of Meis2 in mice and shown that systemic inactivation of the Meis2 gene results in lethality by the embryonic day 14 that is accompanied with hemorrhaging. RESULTS: We show that neural crest cells express Meis2 and Meis2-defficient embryos display defects in tissues that are derived from the neural crest, such as an abnormal heart outflow tract with the persistent truncus arteriosus and abnormal cranial nerves. The importance of Meis2 for neural crest cells is further confirmed by means of conditional inactivation of Meis2 using crest-specific AP2α-IRES-Cre mouse. Conditional mutants display perturbed development of the craniofacial skeleton with severe anomalies in cranial bones and cartilages, heart and cranial nerve abnormalities. CONCLUSIONS: Meis2-null mice are embryonic lethal. Our results reveal a critical role of Meis2 during cranial and cardiac neural crest cells development in mouse.


Assuntos
Nervos Cranianos/embriologia , Coração/embriologia , Proteínas de Homeodomínio/genética , Crista Neural/embriologia , Crânio/embriologia , Animais , Cartilagem/anormalidades , Cartilagem/embriologia , Fatores de Transcrição Forkhead/biossíntese , Fatores de Transcrição Forkhead/genética , Cardiopatias Congênitas/embriologia , Cardiopatias Congênitas/genética , Hemorragia/genética , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Crista Neural/metabolismo , Proteínas Repressoras/biossíntese , Proteínas Repressoras/genética , Fatores de Transcrição SOX9/biossíntese , Fatores de Transcrição SOX9/genética , Crânio/inervação
13.
Anat Rec (Hoboken) ; 298(11): 1824-35, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26054056

RESUMO

Recent studies have highlighted the mechanism of vascular and axonal guidance to ensure proper morphogenesis and organogenesis. We aimed to perform global mapping of developing neurovascular networks during craniofacial development of embryonic mice. To this end, we developed histology-based three-dimensional (3D) reconstructions using paraffin-embedded serial sections obtained from mouse embryos. All serial sections were dual-immunolabeled with Pecam1 and Pgp9.5/Gap43 cocktail antibodies. All immunolabeled serial sections were digitized with virtual microscopy to acquire high spatial resolution images. The 3D reconstructs warranted superior positional accuracy to trace the long-range connectivity of blood vessels and individual cranial nerve axons. It was feasible to depict simultaneously the details of angiogenic sprouting and axon terminal arborization and to assess quantitatively the locoregional proximity between blood vessels and cranial nerve axons. Notably, 3D views of the craniofacial region revealed the following: Branchial arch arteries and blood capillary plexi were formed without accompanying nerves at embryonic day (E) 9.5. Cranial nerve axons began to grow into the branchial arches, developing a labyrinth of small blood vessels at E10.5. Vascular remodeling occurred, and axon terminals of the maxillary, mandibular, chorda tympani, and hypoglossal nerve axons had arborized around the lateral lingual swellings at E11.5. The diverged patterning of trigeminal nerves and the arterial branches from the carotid artery became congruent at E11.5. The overall results support the advantage of dual-immunolabeling and 3D reconstruction technology to document the architecture and wiring of the developing neurovascular networks in mouse embryos.


Assuntos
Axônios , Vasos Sanguíneos/anatomia & histologia , Nervos Cranianos/anatomia & histologia , Face/anatomia & histologia , Imageamento Tridimensional/métodos , Sistema Nervoso/anatomia & histologia , Animais , Nervos Cranianos/embriologia , Face/embriologia , Feminino , Camundongos , Camundongos Endogâmicos ICR , Gravidez
14.
J Anat ; 227(1): 21-33, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-26018729

RESUMO

Craniofacial malformations are common congenital defects caused by failed midline inductive signals. These midline defects are associated with exposure of the fetus to exogenous teratogens and with inborn genetic errors such as those found in Down, Patau, Edwards' and Smith-Lemli-Opitz syndromes. Yet, there are no studies that analyze contributions of synchronous neurocranial and neural development in these disorders. Here we present the first in-depth analysis of malformations of the basicranium of a holoprosencephalic (HPE) trisomy 18 (T18; Edwards' syndrome) fetus with synophthalmic cyclopia and alobar HPE. With a combination of traditional gross dissection and state-of-the-art computed tomography, we demonstrate the deleterious effects of T18 caused by a translocation at 18p11.31. Bony features included a single developmentally unseparated frontal bone, and complete dual absence of the anterior cranial fossa and ethmoid bone. From a superior view with the calvarium plates removed, there was direct visual access to the orbital foramen and hard palate. Both the eyes and the pituitary gland, normally protected by bony structures, were exposed in the cranial cavity and in direct contact with the brain. The middle cranial fossa was shifted anteriorly, and foramina were either missing or displaced to an abnormal location due to the absence or misplacement of its respective cranial nerve (CN). When CN development was conserved in its induction and placement, the respective foramen developed in its normal location albeit with abnormal gross anatomical features, as seen in the facial nerve (CNVII) and the internal acoustic meatus. More anteriorly localized CNs and their foramina were absent or heavily disrupted compared with posterior ones. The severe malformations exhibited in the cranial fossae, orbital region, pituitary gland and sella turcica highlight the crucial involvement of transcription factors such as TGIF, which is located on chromosome 18 and contributes to neural patterning, in the proper development of neural and cranial structures. Our study of a T18 specimen emphasizes the intricate interplay between bone and brain development in midline craniofacial abnormalities in general.


Assuntos
Nervos Cranianos , Holoprosencefalia/genética , Base do Crânio/anormalidades , Trissomia , Cadáver , Cromossomos Humanos Par 18 , Nervos Cranianos/diagnóstico por imagem , Nervos Cranianos/embriologia , Nervos Cranianos/patologia , Feto , Genótipo , Holoprosencefalia/patologia , Humanos , Base do Crânio/diagnóstico por imagem , Base do Crânio/embriologia , Tomografia Computadorizada por Raios X , Síndrome da Trissomía do Cromossomo 18
15.
J Anat ; 226(6): 560-74, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25994127

RESUMO

Cranial foramina are holes within the skull, formed during development, allowing entry and exit of blood vessels and nerves. Once formed they must remain open, due to the vital structures they contain, i.e. optic nerves, jugular vein, carotid artery, and other cranial nerves and blood vessels. Understanding cranial foramina development is essential as cranial malformations lead to the stenosis or complete closure of these structures, resulting in blindness, deafness, facial paralysis, raised intracranial pressure and lethality. Here we focus on describing early events in the formation of the jugular, carotid and hypoglossal cranial foramina that form in the mesoderm-derived, endochondral occipital bones at the base of the embryonic chick skull. Whole-mount skeletal staining of skulls indicates the appearance of these foramina from HH32/D7.5 onwards. Haematoxylin & eosin staining of sections shows that the intimately associated mesenchyme, neighbouring the contents of these cranial foramina, is initially very dense and gradually becomes sparser as development proceeds. Histological examination also revealed that these foramina initially contain relatively large-diameter nerves, which later become refined, and are closely associated with the blood vessel, which they also innervate within the confines of the foramina. Interestingly cranial foramina in the base of the skull contain blood vessels lacking smooth muscle actin, which suggests these blood vessels belong to glomus body structures within the foramina. The blood vessel shape also appears to dictate the overall shape of the resulting foramina. We initially hypothesised that cranial foramina development could involve targeted proliferation and local apoptosis to cause 'mesenchymal clearing' and the creation of cavities in a mechanism similar to joint cavitation. We find that this is not the case, and propose that a mechanism reliant upon local nerve/blood vessel-derived restriction of ossification may contribute to foramina formation during cranial development.


Assuntos
Forame Magno/embriologia , Mesoderma/embriologia , Osso Occipital/embriologia , Animais , Apoptose/fisiologia , Proliferação de Células/fisiologia , Embrião de Galinha , Nervos Cranianos/embriologia , Imuno-Histoquímica , Osso Occipital/irrigação sanguínea
16.
PLoS One ; 10(3): e0120821, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25799573

RESUMO

Cranial nerves govern sensory and motor information exchange between the brain and tissues of the head and neck. The cranial nerves are derived from two specialized populations of cells, cranial neural crest cells and ectodermal placode cells. Defects in either cell type can result in cranial nerve developmental defects. Although several signaling pathways are known to regulate cranial nerve formation our understanding of how intercellular signaling between neural crest cells and placode cells is coordinated during cranial ganglia morphogenesis is poorly understood. Sonic Hedgehog (Shh) signaling is one key pathway that regulates multiple aspects of craniofacial development, but whether it co-ordinates cranial neural crest cell and placodal cell interactions during cranial ganglia formation remains unclear. In this study we examined a new Patched1 (Ptch1) loss-of-function mouse mutant and characterized the role of Ptch1 in regulating Shh signaling during cranial ganglia development. Ptch1(Wig/ Wig) mutants exhibit elevated Shh signaling in concert with disorganization of the trigeminal and facial nerves. Importantly, we discovered that enhanced Shh signaling suppressed canonical Wnt signaling in the cranial nerve region. This critically affected the survival and migration of cranial neural crest cells and the development of placodal cells as well as the integration between neural crest and placodes. Collectively, our findings highlight a novel and critical role for Shh signaling in cranial nerve development via the cross regulation of canonical Wnt signaling.


Assuntos
Nervos Cranianos/embriologia , Proteínas Hedgehog/metabolismo , Via de Sinalização Wnt , Animais , Morte Celular , Movimento Celular , Ectoderma/citologia , Nervo Facial/embriologia , Camundongos , Crista Neural/citologia , Receptores Patched , Receptor Patched-1 , Receptores de Superfície Celular/genética , Receptores de Superfície Celular/metabolismo , Deleção de Sequência , Nervo Trigêmeo/embriologia
17.
Int J Dev Neurosci ; 33: 41-8, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24280100

RESUMO

In zebrafish, cranial sensory circuits form by 4 days post-fertilization. We used a forward genetic screen to identify genes involved in the formation of these circuits. In one mutant allele, sl23, axons arising from the epibranchial sensory ganglia do not form their stereotypical terminal fields in the hindbrain. These embryos also had small eyes and deformed jaws, suggesting a pleiotropic effect. Using positional cloning, a 20-nucleotide deletion in the carbamoyl-phosphate-synthetase2-aspartate-transcarbamylase-dihydroorotase (cad) gene was found. Injection of a CAD morpholino phenocopied the mutant and mutants were rescued by injection of cad RNA. Cad activity is required for pyrimidine biosynthesis, and thus is a prerequisite for nucleic acid production and UDP-dependent protein glycosylation. Perturbation of nucleic acid biosynthesis can result in cell death. sl23 mutants did not exhibit elevated cell death, or gross morphological changes, in their hindbrains. To determine if defective protein glycosylation was involved in the aberrant targeting of sensory axons, we treated wild type embryos with tunicamycin, which blocks N-linked protein glycosylation. Interference with glycosylation via tunicamycin treatment mimicked the sl23 phenotype. Loss of cad reveals a critical role for protein glycosylation in cranial sensory circuit formation.


Assuntos
Aspartato Carbamoiltransferase/metabolismo , Nervos Cranianos , Regulação da Expressão Gênica no Desenvolvimento/fisiologia , Animais , Animais Geneticamente Modificados , Aspartato Carbamoiltransferase/genética , Nervos Cranianos/embriologia , Nervos Cranianos/enzimologia , Nervos Cranianos/crescimento & desenvolvimento , Embrião não Mamífero , Regulação da Expressão Gênica no Desenvolvimento/efeitos dos fármacos , Regulação da Expressão Gênica no Desenvolvimento/genética , Glicosilação , Proteínas de Fluorescência Verde/genética , Proteínas de Fluorescência Verde/metabolismo , Larva , Morfolinos/farmacologia , Tunicamicina/farmacologia , Peixe-Zebra
18.
Dis Model Mech ; 7(2): 245-57, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24357327

RESUMO

We assessed feeding-related developmental anomalies in the LgDel mouse model of chromosome 22q11 deletion syndrome (22q11DS), a common developmental disorder that frequently includes perinatal dysphagia--debilitating feeding, swallowing and nutrition difficulties from birth onward--within its phenotypic spectrum. LgDel pups gain significantly less weight during the first postnatal weeks, and have several signs of respiratory infections due to food aspiration. Most 22q11 genes are expressed in anlagen of craniofacial and brainstem regions critical for feeding and swallowing, and diminished expression in LgDel embryos apparently compromises development of these regions. Palate and jaw anomalies indicate divergent oro-facial morphogenesis. Altered expression and patterning of hindbrain transcriptional regulators, especially those related to retinoic acid (RA) signaling, prefigures these disruptions. Subsequently, gene expression, axon growth and sensory ganglion formation in the trigeminal (V), glossopharyngeal (IX) or vagus (X) cranial nerves (CNs) that innervate targets essential for feeding, swallowing and digestion are disrupted. Posterior CN IX and X ganglia anomalies primarily reflect diminished dosage of the 22q11DS candidate gene Tbx1. Genetic modification of RA signaling in LgDel embryos rescues the anterior CN V phenotype and returns expression levels or pattern of RA-sensitive genes to those in wild-type embryos. Thus, diminished 22q11 gene dosage, including but not limited to Tbx1, disrupts oro-facial and CN development by modifying RA-modulated anterior-posterior hindbrain differentiation. These disruptions likely contribute to dysphagia in infants and young children with 22q11DS.


Assuntos
Deleção Cromossômica , Nervos Cranianos/embriologia , Nervos Cranianos/patologia , Transtornos de Deglutição/embriologia , Transtornos de Deglutição/patologia , Animais , Animais Recém-Nascidos , Padronização Corporal/genética , Anormalidades Craniofaciais/patologia , Anormalidades Craniofaciais/fisiopatologia , Deglutição , Transtornos de Deglutição/genética , Transtornos de Deglutição/fisiopatologia , Síndrome de DiGeorge , Modelos Animais de Doenças , Embrião de Mamíferos/anormalidades , Embrião de Mamíferos/patologia , Comportamento Alimentar , Feminino , Dosagem de Genes , Regulação da Expressão Gênica no Desenvolvimento , Masculino , Camundongos , Fenótipo , Rombencéfalo/anormalidades , Rombencéfalo/embriologia , Rombencéfalo/patologia , Transdução de Sinais , Proteínas com Domínio T/metabolismo , Tretinoína/metabolismo
19.
Neural Dev ; 8: 18, 2013 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-24044555

RESUMO

BACKGROUND: Circuit formation in the nervous system essentially relies on the proper development of neurons and their processes. In this context, the ubiquitin ligase Nedd4 is a crucial modulator of axonal and dendritic branching. RESULTS: Herein we characterize the Nedd4-binding protein 3 (N4BP3), a Fezzin family member, during nerve cell development. In developing rat primary hippocampal neurons, endogenous N4BP3 localizes to neuronal processes, including axons and dendrites. Transient in vitro knockdown of N4BP3 in hippocampal cultures during neuritogenesis results in impaired branching of axons and dendrites. In line with these findings, in vivo knockdown of n4bp3 in Xenopus laevis embryos results in severe alteration of cranial nerve branching. CONCLUSIONS: We introduce N4BP3 as a novel molecular element for the correct branching of neurites in developing neurons and propose a central role for an N4BP3-Nedd4 complex in neurite branching and circuit formation.


Assuntos
Axônios/metabolismo , Proteínas de Transporte/fisiologia , Dendritos/metabolismo , Hipocampo/embriologia , Hipocampo/metabolismo , Animais , Axônios/ultraestrutura , Proteínas de Transporte/química , Proteínas de Transporte/metabolismo , Células Cultivadas , Nervos Cranianos/embriologia , Nervos Cranianos/metabolismo , Dendritos/ultraestrutura , Cones de Crescimento/metabolismo , Proteínas do Tecido Nervoso , Estrutura Terciária de Proteína , Ratos , Xenopus
20.
Acta Neurochir (Wien) ; 154(7): 1119-26, 2012 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-22638594

RESUMO

BACKGROUND: Eagle's syndrome refers to a rare constellation of neuropathic and vascular occlusive symptoms caused by pathologic elongation or angulation of the styloid process and styloid chain. First described in 1652 by Italian surgeon Piertro Marchetti, the clinical syndrome was definitively outlined by Watt Eagle in the late 1940s and early 1950s. METHODS: This article reviews how underlying embryologic and anatomic pathology predicts clinical symptomatology, diagnosis, and ultimately treatment of the syndrome. RESULTS: The length and direction of the styloid process and styloid chain are highly variable. This variability leads to a wide range of relationships between the chain and the neurovascular elements of the neck, including cranial nerves 5, 7, 9, and 10 and the internal carotid artery. In the classic type of Eagle's syndrome, compressive cranial neuropathy most commonly leads to the sensation of a foreign body in the throat, odynophagia, and dysphagia. In the carotid type, compression over the internal carotid artery can cause pain in the parietal region of the skull or in the superior periorbital region, among other symptoms. CONCLUSIONS: Careful recording of the history of the present illness and review of systems is crucial to the diagnosis of Eagle's syndrome. After the clinical examination, the optimal imaging modality for styloid process pathology is spiral CT of the neck and skull base. Surgical interventions are considered only after noninvasive therapies have failed, the two most common being intraoral and external resection of the styloid process.


Assuntos
Ossificação Heterotópica/cirurgia , Angiografia , Animais , Artérias Carótidas/embriologia , Artérias Carótidas/patologia , Nervos Cranianos/embriologia , Nervos Cranianos/patologia , Humanos , Interpretação de Imagem Assistida por Computador , Imageamento Tridimensional , Ossificação Heterotópica/embriologia , Ossificação Heterotópica/patologia , Filogenia , Base do Crânio/embriologia , Base do Crânio/patologia , Osso Temporal/anormalidades , Osso Temporal/embriologia , Osso Temporal/patologia , Osso Temporal/cirurgia , Tomografia Computadorizada por Raios X
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