TL;DR: The tissue and cellular basis of neurulation is reviewed and strategies to determine its molecular basis are provided, expecting that such strategies will lead to the identification in the near future of critical neurulation genes, genes that when mutated perturb neurulation in a highly specific and predictable fashion and cause neurulation defects, thereby contributing to the formation of neural tube defects.
Abstract: Neurulation occurs during the early embryogenesis of chordates, and it results in the formation of the neural tube, a dorsal hollow nerve cord that constitutes the rudiment of the entire adult central nervous system. The goal of studies on neurulation is to understand its tissue, cellular and molecular basis, as well as how neurulation is perturbed during the formation of neural tube defects. The tissue basis of neurulation consists of a series of coordinated morphogenetic movements within the primitive streak (e.g., regression of Hensen's node) and nascent primary germ layers formed during gastrulation. Signaling occurs between Hensen's node and the nascent ectoderm, initiating neurulation by inducing the neural plate (i.e., actually, by suppressing development of the epidermal ectoderm). Tissue movements subsequently result in shaping and bending of the neural plate and closure of the neural groove. The cellular basis of the tissue movements of neurulation consists of changes in the behavior of the constituent cells; namely, changes in cell number, position, shape, size and adhesion. Neurulation, like any morphogenetic event, occurs within the milieu of generic biophysical determinants of form present in all living tissues. Such forces govern and to some degree control morphogenesis in a tissue-autonomous manner. The molecular basis of neurulation remains largely unknown, but we suggest that neurulation genes have evolved to work in concert with such determinants, so that appropriate changes occur in the behaviors of the correct populations of cells at the correct time, maximizing the efficiency of neurulation and leading to heritable species- and axial-differences in this process. In this article, we review the tissue and cellular basis of neurulation and provide strategies to determine its molecular basis. We expect that such strategies will lead to the identification in the near future of critical neurulation genes, genes that when mutated perturb neurulation in a highly specific and predictable fashion and cause neurulation defects, thereby contributing to the formation of neural tube defects.
TL;DR: The traditional viewpoint of how neurulation occurs is evaluated and several cell behaviors within the neural plate have been elucidated, leading to the formulation of the following fundamentals.
Abstract: In this review article, the traditional viewpoint of how neurulation occurs is evaluated in light of recent advances. This has led to the formulation of the following fundamentals: (1) neurulation, specifically neural plate shaping and bending, is a multifactorial process resulting from forces both intrinsic and extrinsic to the neural plate; (2) neurulation is driven by both changes in neuroepithelial cell shape and other form-shaping events; and (3) forces for cell shape changes are generated by both the cytoskeleton and other factors. Several cell behaviors within the neural plate have been elucidated. Future challenges include identifying cell behaviors within non-neuroepithelial tissues, determining how intrinsic and extrinsic cell behaviors are orchestrated into coordinated morphogenetic movements and elucidating the molecular mechanisms underlying such behaviors.
TL;DR: It is shown, by using region-specific neural markers and lineage tracing, that posterior axial tissue induces midbrain and hindbrain fates from prospective forebrain, and a novel activity for the growth factor bFGF in neural patterning is identified.
Abstract: In order to study anteroposterior neural patterning in Xenopus embryos, we have developed a novel assay using explants and tissue recombinants of early neural plate. We show, by using region-specific neural markers and lineage tracing, that posterior axial tissue induces midbrain and hindbrain fates from prospective forebrain. The growth factor bFGF mimics the effect of the posterior dorsal explant in that it (i) induces forebrain to express hindbrain markers, (ii) induces prospective hindbrain explants to make spinal cord, but not forebrain and midbrain, and (iii) induces posterior neural fate in ectodermal explants neuralized by the dominant negative activin receptor and follistatin without mesoderm induction. The competence of forebrain explants to respond to both posterior axial explants and bFGF is lost by neural groove stages. These findings demonstrate that posterior neural fate can be derived from anterior neural tissue, and identify a novel activity for the growth factor bFGF in neural patterning. Our observations suggest that full anteroposterior neural patterning may be achieved by caudalization of prospective anterior neural fate in the vertebrate embryo.
TL;DR: The present study examined human embryos in which the NT was closing grossly and histologically, and found that NT closure in human embyos initiates at multiple sites but that the mode of NTclosure in humans is different from that in many other animal species.
Abstract: The closure of the neural tube (NT) in the human embryo has generally been described as a continuous process that begins at the level of the future cervical region and proceeds both rostrally and caudally. On the other hand, multiple initiation sites of NT closure have been demonstrated in mice and other animals. In humans, based on the study of neural tube defects (NTD) in clinical cases, van Allen et al. (1993) proposed a multisite NT closure model in which five closure sites exist in the NT of human embryos. In the present study, we examined human embryos in which the NT was closing (Congenital Anomaly Research Center, Kyoto University) grossly and histologically, and found that NT closure in human embryos initiates at multiple sites but that the mode of NT closure in humans is different from that in many other animal species. In addition to the future cervical region that is widely accepted as an initiation site of NT closure (Site A), the mesencephalic-rhombencephalic boundary was found to be another initiation site (Site B). The second closure initiating at Site B proceeds bidirectionally and its caudal extension meets the first closure from Site A over the rhombencephalon, and the rostral extension of the second closure meets another closure extending from the rostral end of the neural groove (Site C) over the prosencephalon, where the anterior neuropore closes. The caudal extension of the first closure initiating at Site A was found to proceed all the way down to the caudal end of the neural groove where the posterior neuropore is formed, indicating that in humans, NT closure does not initiate at the caudal end of the neural groove to proceed rostrally. Since there is a considerable species difference in the mode of NT closure, we should be careful when extrapolating the data from other animals to the human. It seems that the type of NTD affects the intrauterine survival of abnormal embryos. Almost all the embryos with total dysraphism appear to die by 5 weeks of gestation, those with an opening over the rhombencephalon by 6.5 weeks, and those with a defect at the frontal and parietal regions survive beyond 7 weeks.
TL;DR: The development of the central nervous system is largely intra-epithelial and thus different from the development of most other organs, and interactions between the neural epithelium and the mesoderm are negligible.
Abstract: In spite of close scrutiny during the last decades, most of the mechanisms that govern neural development remain unknown. Yet, in addition to an obvious theoretical interest, understanding of these principles is requisite to the effective management of human brain malformations and mental retardation. Present views on the development of the central nervous system can be schematized as follows. The CNS derives from the embryonic epiblast. An initial neural plate becomes hollow (neural groove) and closes into the neural tube. As it does so, it sends into the mesoderm a contingent of cells known as the neural crest. The cavity of the neural tube gives rise to the ventricular system, whereas the neural parenchyma derives from its walls. It is worth pointing out that the development of the CNS is largely intra-epithelial and thus different from the development of most other organs. Of course, this does not imply that interactions between the neural epithelium and the mesoderm are negligible. For example, the observation that Cajal-Retzius cells keep contact with the basal lamina by radial processes may be relevant to their function (Derer 1979).