Biomedical subjects

Sophie Creuzet

Publications and source records attributed to Sophie Creuzet.

9 recordsLinked to original sources

PubMed2006

The contribution of the neural crest to the vertebrate body.

As a transitory structure providing adult tissues of the vertebrates with very diverse cell types, the neural crest (NC) has attracted for long the interest of developmental biologists and is still the subject of ongoing research in a variety of animal models. Here we review a number of data from in vivo cell tracing and in vitro single cell culture experiments, which gained new insights on the mechanisms of cell migration, proliferation and differentiation during NC ontogeny. We put emphasis on the role of Hox genes, morphogens and interactions with neighbouring tissues in specifying and patterning the skeletogenic NC cells in the head. We also include advances made towards characterizing multipotent stem cells in the early NC as well as in various NC derivatives in embryos and even in adult.

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PubMed2005

Patterning the neural crest derivatives during development of the vertebrate head: insights from avian studies.

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.

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PubMed2005

In vivo methods to analyze cell origins, migrations, homing, and interactions in the blood, vascular, and immune systems of the avian and mammalian embryo.

In vivo experimental approaches that have been designed to study the ontogeny of the hematopoietic system in higher vertebrates are described in the present chapter. The avian embryo is directly available to manipulations in ovo during gastrulation and organogenesis. This permissiveness has led to the design of various approaches that provided crucial insights into the ontogeny of the hematopoietic system, particularly regarding traffic of progenitors between different compartments. In contrast, experimental manipulation of the developing mouse in utero is possible only during the second half of gestation, that is, the fetal period. This approach has been very useful in understanding how the immune system learns to distinguish self from nonself.

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PubMed2005

Neural crest derivatives in ocular and periocular structures.

In vertebrates, the eye is an ectodermal compound structure associating neurectodermal and placodal anlagen. In addition, it benefits early on from a mesenchymal ectoderm-derived component, the neural crest. In this respect, the construction of chimeras between quail and chick has been a turning point, instrumental in appraising the contribution of the cephalic neural crest to the development of ocular and periocular structures. Given the variety of crest derivatives underscored in the developing eye, this study illustrates the fascinating ability of this unique structure to finely adapt its differentiation to microenvironmental cues. This analysis of neural crest cell contribution to ocular development emphasizes their paramount role to design the anterior segment of the eye, supply refracting media and contribute to the homeostasy of the anterior optic chamber.

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PubMed2004

Reciprocal relationships between Fgf8 and neural crest cells in facial and forebrain development.

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 (i) exogenous FGF8 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 mesenchyme of BA1, and (ii) expression of Fgf8 in forebrain and in BA ectoderm is subjected to signal(s) arising from NC cells, thus showing that the development of cephalic NC-derived structures depends on FGF8 signaling, which is itself triggered by the NC cells.

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PubMed2004

Neural crest cell plasticity and its limits.

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.

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PubMed2003

Patterning of the hyoid cartilage depends upon signals arising from the ventral foregut endoderm.

Hyoid bone is a part of the visceral skeleton which arises from both Hox-expressing (Hox+) and Hox-nonexpressing (Hox-) cephalic neural crest cells. In a previous work, we have demonstrated that the Hox- neural crest domain behaves as a naïve entity to which the ventral foregut endoderm confers patterning cues to specify the shape and orientation of the nasal and mandibular skeleton. By using ablation and grafting approaches, we have extended our study to the formation of the hyoid bone and tested the patterning ability of more caudal levels of the lateroventral foregut endoderm in the chick embryo at the early neurula stage. In this study, endodermal stripes have first been delineated according to the projection of mid- and posterior rhombencephalic structures. The extirpation of endodermal transverse stripes along the anteroposterior axis selectively hampers the formation of the ceratobranchials and epibranchials. Thus defined, the patterning ability of the endodermal stripes was further explored in their medial and lateral parts. When homotopically engrafted on the migration pathway of cephalic neural crest cells, ventromedial zones of endoderm lead to the formation of supernumerary basihyal and basibranchial, while lateral zones generate additional cartilaginous pieces recognizable as ceratobranchial and epibranchial. Taken together, our data demonstrate that, early in development, the ventral foregut endoderm exerts a regionalized patterning activity on the cephalic neural crest to build up the primary facial and visceral skeleton in jaws and neck and enable a map of the endodermal skeletogenic areas to be drawn. This map reveals that a cryptic metamerization of the anterior foregut endoderm precedes the formation of the branchial arches.

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PubMed2002

Negative effect of Hox gene expression on the development of the neural crest-derived facial skeleton.

Diencephalic, mesencephalic and metencephalic neural crest cells are skeletogenic and derive from neural folds that do not express Hox genes. In order to examine the influence of Hox gene expression on skull morphogenesis, expression of Hoxa2, Hoxa3 and Hoxb4 in conjunction with that of the green fluorescent protein has been selectively targeted to the Hox-negative neural folds of the avian embryo prior to the onset of crest cell emigration. Hoxa2 expression precludes the development of the entire facial skeleton. Transgenic Hoxa2 embryos such as those from which the Hox-negative domain of the cephalic neural crest has been removed have no upper or lower jaws and no frontonasal structures. Embryos subjected to the forced expression of Hoxa3 and Hoxb4 show severe defects in the facial skeleton but not a complete absence of facial cartilage. Hoxa3 prevents the formation of the skeleton derived from the first branchial arch, but allows the development (albeit reduced) of the nasal septum. Hoxb4, by contrast, hampers the formation of the nasal bud-derived skeleton, while allowing that of a proximal (but not distal) segment of the lower jaw. The combined effect of Hoxa3 and Hoxb4 prevents the formation of facial skeletal structures, comparable with Hoxa2. None of these genes impairs the formation of neural derivatives of the crest. These results suggest that over the course of evolution, the absence of Hox gene expression in the anterior part of the chordate embryo was crucial in the vertebrate phylum for the development of a face, jaws and brain case, and, hence, also for that of the forebrain.

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PubMed2002

Interactions between Hox-negative cephalic neural crest cells and the foregut endoderm in patterning the facial skeleton in the vertebrate head.

The vertebrate face contains bones that differentiate from mesenchymal cells of neural crest origin, which colonize the median nasofrontal bud and the first branchial arches. The patterning of individual facial bones and their relative positions occurs through mechanisms that remained elusive. During the early stages of head morphogenesis, an endodermal cul-de-sac, destined to become Sessel's pouch, underlies the nasofrontal bud. Reiterative outpocketings of the foregut then form the branchial pouches. We have tested the capacity of endoderm of the avian neurula to specify the facial skeleton by performing ablations or grafts of defined endodermal regions. Neural crest cells that do not express Hox genes respond to patterning cues produced regionally in the anterior endoderm to yield distinct skeletal components of the upper face and jaws. However, Hox-expressing neural crest cells do not respond to these cues. Bone orientation is likewise dependent on the position of the endoderm relative to the embryonic axes. Our findings thus indicate that the endoderm instructs neural crest cells as to the size, shape and position of all the facial skeletal elements, whether they are cartilage or membrane bones.

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