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

Abstract

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.cephalic neural crest ͉ facial skeleton ͉ forebrain ͉ regeneration ͉ quail-chick chimeras I n vertebrates, the skeleton and connective components of the face are derived from the cephalic neural crest (NC), which can be divided into two domains. The first, a rostral domain, in which no Hox genes are expressed, extends from the presumptive level of the epiphysis down through the second rhombomere (r2); it yields the cartilages and membrane bones of the face (Fig. 1 A). It is referred to here as the facial skeletogenic NC (FSNC). The second, posterior domain (from r4 through r8) generates part of the hyoid cartilages and does not form any membrane bone. In this posterior domain of the NC, Hox genes of the four first paralogous groups are expressed both in neural tube and NC (1-3). A few NC cells (NCC) from r3 contribute to both domains. However, this contribution to branchial arches (BAs) is very small because most r3-derived NCC are undergoing apoptosis (4, 5).When the entire Hox-negative domain of the NC is removed, no facial structures develop, meaning that Hox-expressing NCC do not substitute for the Hox-negative ones (6, 7). In contrast, any fragment of the Hox-negative crest, grafted in the anterior cephalic region following the ablation of the FSNC, can regenerate a normal face (6). Thus, the Hox-negative crest behaves as an equivalence group showing that, at the early stages, the crest cells themselves do not possess the information to construct the specific bones and cartilages that constitute the facial skeleton. The ventrolateral endoderm of the foregut is able to provide the NCC with the information necessary for patterning the facial skeleton and also the hyoid cartilage (6,8). Later in development of the facial structures, the ectoderm of the facial process also participates in the final patterning of the beak (9, 10).The investigations reported here were prompted by the observation that removal of the FSNC resulted in a dramatic decrease of Fgf8 expression in the forebrain anlage, as well as in the BA ectoderm ( Fig. 1 B-E). This was followed by the t...

The function and regulation of TBX22 in avian frontonasal morphogenesis

“…There is also FGF8 expressed in the rostral/anterior telencephalon (Creuzet et al, 2004;Hu and Marcucio, 2009). Thus, the thin layer of frontonasal mass mesenchyme is sandwiched between two FGF8-expressing tissues.…”

Precocious puberty in a patient with Oculo-Auriculo-Verebral spectrum (OAVS)

“…the prosencephalic organizer) and the development of pre-otic brain and of diencephalon and mesencephalon. However they also control the Fgf in branchial arch ectoderm 21,22 and the development of craniofacial structures. This condition explains why hypothalamic pituitary dysfunction is frequently associated with a variety of prechordal malformations of the skull base.…”

Embryologie de la face et dysplasies otomandibulaires

“…Des expériences de perte-de-fonction restreintes à l'ectoderme sont accompagnées d'un défaut de migration des CCN dans les territoires sous-jacents et privent les bourgeons faciaux de mésenchyme squelettogénique [11].…”

“…Le phéno-type résultant de l'extirpation de la CN antérieure consiste en l'absence de structures faciales accompagnée des déficits sévères du développement prosencéphalique. Chez ces embryons, soumis à l'apport d'une source exogène de FGF8, les cellules de crête issues du 3 e rhombomère (situées à la limite postérieure du territoire excisé et qui normalement fournissent très peu de mésenchyme au 1 er arc) présentent une capacité invasive accrue, prolifèrent considérablement et développent un statut globalement Hox-négatif : elles sont alors capables de régé-nérer la totalité du squelette maxillaire et mandibulaire [11].…”

“…Celles-ci impliquent des influences réciproques liant le devenir des CCN (à l'origine des cellules squelettogéniques) aux épithéliums adjacents tant ectodermiques qu'endodermiques qui fournissent les signaux trophiques et morphogénétiques [2,7,11,45,46].…”