The cephalic neural crest exerts a critical effect on forebrain and midbrain development

Abstract

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.Fgf8 ͉ exencephaly ͉ preotic vesicles ͉ prosencephalic organizer ͉ quail-chick chimeras F ate mapping experiments conducted in the avian embryo and based on the construction of quail chick chimeras have led to the notion that the facial and hypobranchial skeletons are derived from neural crest (NC) cells (NCC) migrating from the mid-diencephalon down to rhombomere (r)8 (1, 2). This domain is divided into two parts. The rostral part yields the entire facial skeleton, designated facial skeletogenic NC (FSNC), in which no genes of Hox clusters are expressed, and the posterior part yields the middle and posterior parts of the hyoid bone, in which Hox genes of the four first paralogue groups are expressed (Fig. 3, which is published as supporting information on the PNAS web site). The limit between these two domains corresponds to r3, the NCC of which play a pivotal role between the rostral Hoxnegative and the caudal Hox-positive NCC populations (3-6). Some r3 NCC migrate to branchial arch (BA)1, whereas others diverge to participate in BA2. The former lose their Hoxa2 expression during the migration, whereas the latter maintain it within the BA2 environment.Experiments in which the Hox-negative neural fold (NF) was removed before NCC emigration (Fig. 1 A-C) resulted in the complete absence of facial skeleton, whereas only a third of the anterior, Hox-negative territory left in situ (or grafted from quail to chick) was sufficient to generate a complete face. These and other data (7-9) led us to consider that Hox-positive cephalic NCC cannot substitute for their Hox-negative counterpart i...

Evolution of the neural crest viewed from a gene regulatory perspective

“…The second difference between the neural crest network of lamprey and gnathostome vertebrates is that some transcription factors, like Ets1 and Twist, which function as neural crest specifier genes in higher vertebrates, are deployed very late, at the level of effector genes, in the lamprey (Creuzet et al, 2006;Linker et al, 2000;Maroulakou et al, 1994;Meyer et al, 1997;SaukaSpengler et al, 2007;Tahtakran and Selleck, 2003). The cumulative results suggest that a neural crest gene regulatory network existed at the base of vertebrates, albeit slightly modified from that hypothesized to occur during gnathostome development.…”

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

“…In some families, a dominant or recessive autosomal inheritance was reported, while in others OAVS was sporadic 14 . Various chromosome rearrangements or deletions were reported in associations with OAVS, (chromosomes 1,5,6,8,18,22) 23 . We previously reported a case of OAVS associatd with a microdeletion of chromosome 1, i.e.…”

“…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.…”

Cell lineages and early patterns of embryonic CNS vascularization

“…While some inductive mechanisms are similar in the spinal cord and the forebrain, like ventral Shh and dorsal BMP expression, others are dissimilar, like dorsal Pax6 expression in the forebrain 6 vs ventral expression in the spinal cord. 5 The details are clearly beyond the scope of this article, but four important differences between the developing spinal cord and the brain anlagen should be pointed out: (1) the brain primordium is segmented (best studied in the so-called rhombomeres of the hindbrain), while the spinal NT is not; 7,8 (2) the NC of the brain (cephalic NC) produces most tissues of the face and skull (notably, vascular smooth muscle cells, vSMC 9 ), in addition to those cell types the spinal NC can give rise to, 10 and is important for forebrain development; 11,12 (3) especially in the cerebellum and the mammalian telencephalon, their enormous size is associated with additional proliferating zones and neuronal migration, and a more complex layering of neuroblasts and neurons; (4) the retina and optic nerve, and the olfactory bulb represent highly specialized extensions of the forebrain.…”

“…Cephalic NC contributes the majority of head mesenchyme, and thus connective tissue cells to the meninges of the brain, and mural cells (PC and vSMC) to the vascular walls of both PNVP and intraneural vessels. 9,11 Both an early immigration of PC shortly after or together with EC, 56 and immigration of PC in advance of EC into the brain 57 or retina 58 were described. We showed that, as an alternative to immigration of NC-derived cells, direct differentiation of neuroblasts to PC was possible 22 (Fig.…”