Malformations affecting the nervous system in humans are numerous and various in etiology. Many are due to genetic deficiencies or mechanical accidents occurring at early stages of development. It is thus of interest to reproduce such human malformations in animal models. The avian embryo is particularly suitable for researching the role of morphogenetic movements and genetic signaling during early neurogenesis. The last ten years of research with Nicole Le Douarin in the Nogent Institut have brought answers to questions formulated by Etienne Wolff at the beginning of his career, by showing that Hensen's node, the avian organizer, is at the source of all the midline cells of the embryo and ensures cell survival, growth and differentiation of neural and mesodermal tissues.
KEY WORDS: neurulation, Hensen's node, floor plate, quail-chick chimera, caudal dysplasia
ForewordEtienne Wolff, the founder of the Nogent Institute, was a pioneer in teratogenic studies. He was the first to use the chick embryo as an animal model to construct phenocopies of human developmental malformations (Wolff, 1936). During his PhD thesis under the supervision of Paul Ancel in Strasbourg University, he experimentally reproduced cyclopia and symmelia, two dramatic malformations occasionally observed in human embryos, affecting organ bilaterality. He obtained phenocopies of such malformations in bird embryos by performing axial organ destruction using X irradiation at early stages of development (Fig. 1). Sixty years after these pioneer experiments, with Nicole Le Douarin, a former student of Etienne Wolff and his successor at the head of the Nogent Institute, we used the quail-chick cell labeling technique (Le Douarin, 1969) and microsurgical excision to elucidate the role of the avian organizer, Hensen's node, during the development of the central nervous system in the avian embryo. The results that we obtained confirmed and extended Wolff's observations and, like them, could be related to known human malformations. In the present paper we will review several aspects of our recent work, the aim of which was to improve our general understanding of the early development of the vertebrate nervous system.
The first stages of neurogenesis: «primary» versus «secondary» neurulationIn birds, as in other chordates, a region of the primitive ectoderm is precociously induced to form the neurectoderm (Stern, 2002 for a review). Neural induction leads to the formation of a prismatic cell layer organized into the so-called neural plate. This plate will undergo a series of subsequent morphogenetic movements called neurulation, giving rise to the neural tube, i.e., the primordium of the central nervous system (CNS). Vertebrate neurulation proceeds according to two different mechanisms regarding the type of cell movements implicated (Catala et al., 1995;Colas and Schoenwolf, 2001 and references therein). In the first, which affects the anterior moiety of the bird embryo, the neural plate bends due to the formation of several hinge points (one me...
