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The neural crest, a unique cell population originating from the primitive neural field, has a multi-systemic and structural contribution to vertebrate development. At the cephalic level, the neural crest generates most of the skeletal tissues encasing the developing forebrain and provides the prosencephalon with functional vasculature and meninges. Over the last decade, we have demonstrated that the cephalic neural crest (CNC) exerts an autonomous and prominent control on the development of the forebrain and sense organs. The present paper reviews the primary mechanisms by which CNC can orchestrate vertebrate encephalization. Demonstrating the role of the CNC as an exogenous source of patterning for the forebrain provides a novel conceptual framework with profound implications for understanding neurodevelopment. From a biomedical standpoint, these data suggest that the spectrum of neurocristopathies is broader than expected and that some neurological disorders may stem from CNC dysfunctions. [ABSTRACT FROM AUTHOR]

Mutations in effectors of the hedgehog signaling pathway are responsible for a wide variety of ocular developmental anomalies. These range from massive malformations of the brain and ocular primordia, not always compatible with postnatal life, to subtle but damaging functional effects on specific eye components. This review will concentrate on the effects and effectors of the major vertebrate hedgehog ligand for eye and brain formation, Sonic hedgehog (SHH), in tissues that constitute the eye directly and also in those tissues that exert indirect influence on eye formation. After a brief overview of human eye development, the many roles of the SHH signaling pathway during both early and later morphogenetic processes in the brain and then eye and periocular primordia will be evoked. Some of the unique molecular biology of this pathway in vertebrates, particularly ciliary signal transduction, will also be broached within this developmental cellular context. [ABSTRACT FROM AUTHOR]

During the early steps of head development, ectodermal patterning leads to the emergence of distinct non-neural and neural progenitor cells. The induction of the preplacodal ectoderm and the neural crest depends onwell-studied signalling interactions between the non-neural ectoderm fated to become epidermis and the prospective neural plate. By contrast, the involvement of the non-neural ectoderm in the morphogenetic events leading to the development and patterning of the central nervous systemhas been studied less extensively. Here,we show that the removal of the rostral non-neural ectoderm abutting the prospective neural plate at late gastrulation stage leads, in mouse and chick embryos, to morphological defects in forebrain and craniofacial tissues. In particular, this ablation compromises the development of the telencephalon without affecting that of the diencephalon. Further investigations of ablated mouse embryos established that signalling centres crucial for forebrain regionalization, namely the axial mesendoderm and the anterior neural ridge, form normally. Moreover, changes in cell death or cell proliferation could not explain the specific loss of telencephalic tissue. Finally, we provide evidence that the removal of rostral tissues triggers misregulation of the BMP, WNT and FGF signalling pathways that may affect telencephalon development. This study opens new perspectives on the role of the neural/non-neural interface and reveals its functional relevance across higher vertebrates. [ABSTRACT FROM AUTHOR]

The facial neural crest (FNC), a pluripotentembryonic structure forming craniofacial structures, controls the activity of brain organisers and stimulates cerebrum growth. To understand how the FNC conveys its trophic effect, we have studied the role of Smad1, which encodes an intracellular transducer, to which multiple signalling pathways converge, in the regulation of Foxg1. Foxg1 is a transcription factor essential for telencephalic specification, the mutation of which leads to microcephaly andmental retardation. Smad1 silencing, based on RNA interference (RNAi), was performed in pre-migratory FNC cells. Soon after electroporation of RNAi molecules, Smad1 inactivation abolished the expression of Foxg1 in the chick telencephalon, resulting in dramatic microcephaly and partial holoprosencephaly. In addition, the depletion of Foxg1 activity altered the expression Otx2 and Foxa2 in di/ mesencephalic neuroepithelium. However, when mutated forms of Smad1 mediating Fgf and Wnt signalling were transfected into FNC cells, these defects were overcome.We also show that, downstreamof Smad1 activity, Dkk1, aWnt antagonist produced by the FNC, initiated the specification of the telencephalon by regulating Foxg1 activity. Additionally, the activity of Cerberus in FNC-derived mesenchyme synergised with Dkk1 to control Foxg1 expression and maintain the balance between Otx2 and Foxa2. [ABSTRACT FROM AUTHOR]

The combinatorial expression of Hox genes is an evolutionarily ancient program underlying body axis patterning in all Bilateria. In the head, the neural crest (NC)--a vertebrate innovation that contributes to evolutionarily novel skeletal and neural features--develops as a structure free of Hox-gene expression. The activation of Hoxa2 in the Hox-free facial NC (FNC) leads to severe craniofacial and brain defects. Here, we show that this condition unveils the requirement of three Six genes, Six1, Six2, and Six4, for brain development and morphogenesis of the maxillo-mandibular and nasofrontal skeleton. Inactivation of each of these Six genes in FNC generates diverse brain defects, ranging from plexus agenesis to mild or severe holoprosencephaly, and entails facial hypoplasia or truncation of the craniofacial skeleton. The triple silencing of these genes reveals their complementary role in face and brain morphogenesis. Furthermore, we show that the perturbation of the intrinsic genetic FNC program, by either Hoxa2 expression or Six gene inactivation, affects Bmp signaling through the downregulation of Bmp antagonists in the FNC cells. When upregulated in the FNC, Bmp antagonists suppress the adverse skeletal and cerebral effects of Hoxa2 expression. These results demonstrate that the combinatorial expression of Six1, Six2, and Six4 is required for the molecular programs governing craniofacial and cerebral development. These genes are crucial for the signaling system of FNC origin, which regulates normal growth and patterning of the cephalic neuroepithelium. Our results strongly suggest that several congenital craniofacial and cerebral malformations could be attributed to Six genes' misregulation. [ABSTRACT FROM AUTHOR]

The article focuses on the neural crest (NC) and its participation in the evolution process of vertebrates. It notes the studies which suggest that NC does not only provide the cells that build up the facial skeleton and most of the skull but plays a major roll in early brain neurogenesis. It also mentions that the application of a cell marking technique in constructing chimeric embryos between the quail and the chicken has led to show that the vertebrate head is mainly formed by cells from NC.

Emergence of the neural crest (NC) is considered an essential asset in the evolution of the chordate phylum, as specific vertebrate traits such as peripheral nervous system, cephalic skeletal tissues, and head development are linked to the NC and its derivatives. It has been proposed that the emergence of the NC was responsible for the formation of a "new head" characterized by the spectacular development of the forebrain and associated sense organs. It was previously shown that removal of the cephalic NC (CNC) prevents the formation of the facial structures but also results in anencephaly. This article reports on the molecular mechanisms whereby the CNC controls cephalic neurulation and brain morphogenesis. This study demonstrates that molecular variations of Gremlin and Noggin level in CNC account for morphological changes in brain size and development. CNC cells act in these processes through a multi-step control and exert cumulative effects counteracting bone morphogenetic protein signaling produced by the neighboring tissues (e.g., adjacent neuroepithelium, ventromedial mesoderm, superficial ectoderm). These data provide an explanation for the fact that acquisition of the NC during the protochordate-to-vertebrate transition has coincided with a large increase of brain vesicles. [ABSTRACT FROM AUTHOR]

Encephalisation is the most important characteristic in the evolutionary transition leading from protochordates to vertebrates. This event has coincided with the emergence of a transient and pluripotent structure, the neural crest (NC), which is absent in protochordates. In vertebrates, NC provides the rostral cephalic vesicles with skeletal protection and functional vascularization. The surgical extirpation of the cephalic NC, which is responsible for building up the craniofacial skeleton, results in the absence of facial skeleton together with severe defects of preotic brain development, leading to exencephaly. Here, we have analyzed the role of the NC in forebrain and midbrain development. We show that (i) NC cells (NCC) control Fgf8 expression in the anterior neural ridge, which is considered the prosencephalic organizer; (ii) the cephalic NCC are necessary for the closure of the neural tube; and (iii) NCC contribute to the proper patterning of genes that are expressed in the prosencephalic and mesencephalic alar plate. Along with the development of the roof plate, NCC also concur to the patterning of the pallial and subpallial structures. We show that the NC-dependent production of FGF8 in anterior neural ridge is able to restrict Shh expression to the ventral prosencephalon. All together, these findings support the notion that the cephalic NC controls the formation of craniofacial structures and the development of preotic brain. [ABSTRACT FROM AUTHOR]

Studies carried out in the avian embryo and based on the construction of quail–chick chimeras have shown that most of the skull and all the facial and visceral skeleton are derived from the cephalic neural crest (NC). Contribution of the mesoderm is limited to its occipital and (partly) to its otic domains. NC cells (NCCs) participating in membrane bones and cartilages of the vertebrate head arise from the diencephalon (posterior half only), the mesencephalon and the rhombencephalon. They can be divided into an anterior domain (extending down to r2 included) in which genes of the Hox clusters are not expressed (Hox-negative skeletogenic NC) and a posterior domain including r4 to r8 in which Hox genes of the four first paraloguous groups are expressed. The NCCs that form the facial skeleton belong exclusively to the anterior Hox-negative domain and develop from the first branchial arch (BA1). This rostral domain of the crest is designated as FSNC for facial skeletogenic neural crest. Rhombomere 3 (r3) participates modestly to both BA1 and BA2. Forced expression of Hox genes ( Hoxa2, Hoxa3 and Hoxb4) in the neural fold of the anterior domain inhibits facial skeleton development. Similarly, surgical excision of these anterior Hox-negative NCCs results in the absence of facial skeleton, showing that Hox-positive NCCs cannot replace the Hox-negative domain for facial skeletogenesis. We also show that excision of the FSNC results in dramatic down-regulation of Fgf8 expression in the head, namely in ventral forebrain and in BA1 ectoderm. We have further demonstrated that exogenous FGF8 applied to the presumptive BA1 territory at the 5–6-somite stage (5–6ss) restores to a large extent facial skeleton development. The source of the cells responsible for this regeneration was shown to be r3, which is at the limit between the Hox-positive and Hox-negative domain. NCCs that respond to FGF8 by survival and proliferation are in turn necessary for the expression/maintenance of Fgf8 expression in the ectoderm. These results strongly support the emerging picture according to which the processes underlying morphogenesis of the craniofacial skeleton are regulated by epithelial–mesenchymal bidirectional crosstalk. [ABSTRACT FROM AUTHOR]

The neural crest (NC) yields pluripotent cells endowed with migratory properties. They give rise to neurons, glia, melanocytes and endocrine cells, and to diverse 'mesenchymal' derivatives. Experiments in avian embryos have revealed that the differentiation of the NC 'neural' precursors is strongly influenced by environmental cues. The reversibility of differentiated cells (such as melanocytes or glia) to a pluripotent precursor state can even be induced in vitro by a cytokine, endothelin 3. The fate of 'mesenchymal' NC precursors is strongly restricted by Hox gene expression. In this context, however, facial skeleton morphogenesis is under the control of a multistep crosstalk between the epithelia (endoderm and ectoderm) and NC cells. [ABSTRACT FROM AUTHOR]

Fgf8 exerts a strong effect on the mesenchymal cells of neural crest (NC) origin that are fated to form the facial skeleton. Surgical extirpation of facial skeletogenic NC domain (including mid-diencephalon down through rhombomere 2), which does not express Hox genes, results in the failure of facial skeleton development and inhibition of the closure of the forebrain neural tube, while Fgf8 expression in the telencephalon and in the branchial arch (BA) ectoderm is abolished. We demonstrate here that (1) exogenous FGFS is able to rescue facial skeleton development by promoting the proliferation of NC cells from a single rhombomere, r3, which in normal development contributes only marginally to mean-chyme of BAI. and (ii) expression of Fg18 in forebrain and in BA ectoderm is subjected to signal(s) arising from NC cells, thus showing that the development of cephalk NC-derived structures depends on FGF8 signaling. which is itself triggered by the NC cells. [ABSTRACT FROM AUTHOR]