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 speciesand 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.

Serotonin, first described as a neurotransmitter in invertebrates, has been investigated mostly for its functions in the mature central nervous system of higher vertebrates. Serotonin receptor diversity has been described in the mammalian brain and in insects. We report the isolation of a cDNA coding for a Drosophila melanogaster serotonin receptor that displays a sequence, a gene organization, and pharmacological properties typical of the mammalian 5-HT2 serotonin receptor subtype. Its mRNA can be detected in the adult fly; moreover, a high level of expression occurs at 3 hr ofDrosophila embryogenesis. This early embryonic expression is surprisingly organized in a seven-stripe pattern that appears at the cellular blastoderm stage. In addition, this pattern is in phase with that of the even-parasegment-expressed pair-rule gene fushi-tarazu and is similarly modified by mutations affecting segmentation genes. Simultaneously with this pair-rule expression, the complete machinery of serotonin synthesis is present and leads to a peak of ligand concomitant with a peak of 5-HT2-specific receptor sites in blastoderm embryos.In vertebrates, the biogenic amine serotonin (5-hydroxytryptamine, 5-HT) affects a wide variety of behavioral and physiological functions that are mediated by numerous receptor subtypes. These receptors can be classified according to the transduction mechanisms: the 5-HT1 subtype as an adenylyl cyclase inhibitor, 5-HT2 as a phospholipase C stimulator, and 5-HT4, 5-HT6, and 5-HT7 as adenylyl cyclase activators; these are all G protein-coupled receptors. The 5-HT3 subtype is a ligand-gated channel (1). In insects, biogenic amines are similarly implicated as neuromodulators and neurotransmitters (2) in addition to their function of crosslinking proteins and chitin during sclerotization of the cuticle (3). In Drosophila melanogaster, the serotoninergic neurons have been localized (4) and implicated in salivary gland secretion, heart and oviduct contractions, circadian rhythms, and learning and memory (2). 5-HT receptors have also been detected as a heterogeneous population by[3H]5-HT binding experiments or by second-messenger cou-

During Drosophila gastrulation, convergent extension of the ectoderm is required for germband extension. Adhesive heterogeneity within ectodermal cells has been proposed to trigger the intercalation of cells responsible for this movement. Segmentation genes would impose this heterogeneity by establishing a pair-rule pattern of cell adhesion properties. We previously reported that the serotonin receptor (5-ht(2Dro)) is expressed in the presumptive ectoderm with a pair-rule pattern. Here, we show that the peaks of 5-ht(2Dro) expression and serotonin synthesis coincide precisely with the onset of convergent extension of the ectoderm. Gastrulae genetically depleted of serotonin or the 5-ht(2Dro) receptor do not extend their germband properly, and the ectodermal movements becomes asynchronous with the morphogenetic movements in the endoderm and mesoderm. Associated with the beginning of this desynchronisation, is an altered subcellular localisation of adherens junctions within the ectoderm. Combined, these data highlight the role of the ectoderm in Drosophila gastrulation and support the notion that serotonin signalling through the 5-HT(2Dro) receptor triggers changes in cell adhesiveness that are necessary for cell intercalation.