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PubMed1990

Mechanisms of neurulation: traditional viewpoint and recent advances.

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.

Animals↗
PubMed2002

Bimodal functions of Notch-mediated signaling are involved in neural crest formation during avian ectoderm development.

Neural crest is induced at the junction of epidermal ectoderm and neural plate by the mutual interaction of these tissues. In previous studies, BMP4 has been shown to pattern the ectodermal tissues, and BMP4 can induce neural crest cells from the neural plate. In this study, we show that epidermally expressed Delta1, which encodes a Notch ligand, is required for the activation and/or maintenance of Bmp4 expression in this tissue, and is thus indirectly required for neural crest induction by BMP4 at the epidermis-neural plate boundary. Notch activation in the epidermis additionally inhibits neural crest formation in this tissue, so that neural crest generation by BMP4 is restricted to the junction.

Animals↗
PubMed2004

The primitive streak, the caudal eminence and related structures in staged human embryos.

The caudal region of the trunk was reassessed in 52 serially sectioned human embryos of stages 8-23, 42 of which were controlled by precise graphic reconstructions. The following observations, new for the human, are presented. (1) The neurenteric canal is an important landmark because rostral to it the neural plate of stages 8, 9, and the main part of the notochord develop, whereas caudal to it the neural plate of stages 10-12 and the caudal portion of the notochord are formed. All somites at stages 9-11 and probably also at stage 12 arise rostral to the site of the neurenteric canal. (2) A 'chordoneural hinge' can be detected in stages 10 and 11, where the caudal part of the neural plate gives off cells that probably participate in the production of mesenchyme. (3) When apparent disappearance of the epiblast is used as a criterion, then the primitive streak seems to end during stage 9. (4) The caudal eminence, derived from the primitive streak and covered by ectoderm, forms at stage 10 caudal to the site of the former neurenteric canal and persists as a terminal cap to at least stage 14, although formation of mesenchyme continues in stages 15 to 17 or 18. (5) As the region rostral to the site of the neurenteric canal grows because of the development of somites, the caudal eminence is shifted caudally. (6) The caudal eminence is most active developmentally during stage 13, when most of the required (ca 6 out of 9) pairs of somites appear. (7) The eminence produces the caudal part of the notochord and, after closure of the caudal neuropore, all caudal structures, but it does not produce even a temporary 'tail' in the human. (8) A temporal overlap results between primary and secondary development in the caudal part of the notochord. (9) Primary development begins very early with the formation of the inner cell mass at stage 3, and includes the development of the somites rostral to the neurenteric canal, whereas secondary development, with the exception of the notochord caudally, commences at stage 12. (10) Primary neurulation lasts from stage 8 to stage 12, secondary from stage 12 to stages 17 or 18. (11) Secondary development and secondary neurulation are characterized morphologically by direct formation of structures (notochord, postcloacal gut, neural cord/neural tube) from mesenchyme.

Ectoderm↗
PubMed1980

Ultrastructure of secondary neurulation in the chick embryo.

Formation of the future lumbosacral level of the spinal cord was studied in two-day-old chick embryos by light and electron (transmission and scanning) microscopy. A neurulation overlap zone occupied this level. The dorsal portion of the neural tube formed by bending of the neural plate and approximation and fusion of neural folds (i.e., by primary neurulation), and the ventral part formed during secondary neurulation by cavitation of an initially solid, compact mass of cells, the medullary cord, derived from the tail bud. Secondary neurulation involved four morphogenetic processes: (1) segregation of the cells of the prospective medullary cord from cells of adjacent regions, (2) formation of a precisely delimited medullary cord, (3) cavitation of the central portion of this cord, and (4) coalescence of all lumina into a single, central cavity. Cell segregation was associated with the formation of a layer of primarily extracellular materials between adjacent organ rudiments. The source and composition of these materials are unknown. Formation of the medullary cord entailed considerable elongation of the peripheral cells of this developing structure and the fabrication of small intercellular juctions, first at the basal (outer) ends of the elongating peripheral cells, and then at their apical (inner) ends. These arranged, columnar cells, having characteristics similar to those of the neural plate, and an inner cluster of irregularly shaped and arranged cells. Cavitation always occurred first at the junction between these two cellular populations. The central cells of the medullary cord also eventually elongated, like the peripheral cells, and may have been intercalated into the lateral walls of the developing neural tube as lumina coalesced.

Animals↗
PubMed1988

Changes in peanut lectin binding sites on the neuroectoderm during neural tube formation in the bantam chick embryo.

Cell surface carbohydrates in the neurulating ectoderm of bantam chick embryos of stage 6-11 were examined using the fluorescein isothiocyanate-labeled and ferritin-labeled peanut lectin, Arachis hypogaea agglutinin (PNA), which is Gal beta 1----3GalNAc specific. Weak fluorescence showing PNA binding sites was seen on the apical surfaces of neural plate cells. On the surfaces of neural tube cells the fluorescence was more intense and appeared as a band. When using ferritin particles as a quantitative EM marker, only a few PNA binding sites covering the apical surfaces of the basal plate cells during the neural plate stage were seen (274.3 +/- 18.67 ferritin particles/micron 2). As neural tube formation advanced, the number of the ferritin labeled PNA binding sites increased as was to be expected from the fluorescent label experiment. At the neural ridge contact stage there were 2.5 times more binding sites than at the neural plate stage. After this period, the lectin binding sites showed no significant changes. These results were the inverse of those for RCAI or WGA lectins previously reported by us. These observations suggest that sugar residues or the sugar-chain skeletons on the neuroectoderm are altered during neurulation.

Animals↗
PubMed1995

Wnt expression patterns in chick embryo nervous system.

Several lines of evidence suggest that Wnt genes play a critical role in regulating development of the vertebrate embryo. To address the role that this family may play in the development of the chicken central nervous system (CNS), we have used a PCR based strategy to clone partial sequences for Wnt genes. At least six different Wnt genes are expressed in the developing CNS of the chick embryo. The domains of expression overlap either partially or completely, and are expressed in spatial domains that prefigure morphological subunits of the embryonic neural tube. Wnt-1 and Wnt-4 are first expressed in the open neural plate in the region of the presumptive mesencephalon. Wnt-3a expression is first observed in the rhombencephalic regions of the open neural plate. After neural tube closure, when the embryonic subdivisions of the neural tube became apparent, Wnt-1, Wnt-3a and Wnt-4 are all broadly expressed in partially overlapping domains in the mesencephalon and caudal diencephalon, as well as in the rhombencephalon and spinal cord. The mesencephalic expression patterns are subsequently modified such that Wnt-1 and Wnt-4 are expressed in a characteristic ring just rostral to the isthmus, at the mesencephalic/metencephalic junction; and Wnt-1 and Wnt-3a expression become restricted to the dorsal midline. Wnt-1, Wnt-3a, Wnt-4, Wnt-5a and Wnt-8b are expressed in one or two caudal subdivisions of the developing diencephalon, the synencephalon and posterior parencephalon, but do not extend ventral to the zona limitans interparencephalica. In contrast, Wnt-7b is expressed in the anterior parencephalon. Both Wnt-7b and Wnt-8b are expressed in telencephalic portions of the secondary prosencephalon. The timing and spatial distribution of Wnt-gene expression in the chick embryo further support the general hypothesis that Wnt genes play key roles in patterning the developing vertebrate nervous system.

Amino Acid Sequence↗
PubMed1999

Functional association of retinoic acid and hedgehog signaling in Xenopus primary neurogenesis.

Previous work has shown that the posteriorising agent retinoic acid can accelerate anterior neuronal differentiation in Xenopus laevis embryos (Papalopulu, N. and Kintner, C. (1996) Development 122, 3409-3418). To elucidate the role of retinoic acid in the primary neurogenesis cascade, we investigated whether retinoic acid treatment of whole embryos could change the spatial expression of a set of genes known to be involved in neurogenesis. We show that retinoic acid expands the N-tubulin, X-ngnr-1, X-MyT1, X-&Dgr;-1 and Gli3 domains and inhibits the expression of Zic2 and sonic hedgehog in the neural ectoderm, whereas a retinoid antagonist produces opposite changes. In contrast, sonic and banded hedgehog overexpression reduced the N-tubulin stripes, enlarged the neural plate at the expense of the neural crest, downregulated Gli3 and upregulated Zic2. Thus, retinoic acid and hedgehog signaling have opposite effects on the prepattern genes Gli3 and Zic2 and on other genes acting downstream in the neurogenesis cascade. In addition, retinoic acid cannot rescue the inhibitory effect of Notch(ICD), Zic2 or sonic hedgehog on primary neurogenesis. Our results suggest that retinoic acid acts very early, upstream of sonic hedgehog, and we propose a model for regulation of differentiation and proliferation in the neural plate, showing that retinoic acid might be activating primary neurogenesis by repressing sonic hedgehog expression.

Animals↗
PubMed1999

The spatial and temporal pattern of C-Lmx1 expression in the neuroectoderm during chick neurulation.

C-Lmx1 has been shown to be a key regulatory gene for specification of dorsoventral pattern during vertebrate limb development. Here, we describe its earlier pattern of expression during and shortly after neurulation. Transcripts are first expressed in the mesoderm of the head process and rostral tip of the primitive streak at the late gastrula/early neurula stage (stage 4). As neurulation occurs with shaping of the neural plate, C-Lmx1 is expressed in a butterfly-like pattern in the lateral neuroectoderm. During bending of the neural plate, C-Lmx1 expression becomes localized to three areas of the bending neuroectoderm: the median hingepoint (future floor plate of the neural tube) and the paired dorsolateral regions of the neuroepithelium, including the dorsolateral hingepoints and the adjacent neuroectodermal and epidermal ectodermal components of the neural folds. After closure of the neural groove and formation of the primary brain vesicles, C-Lmx1 is expressed in the dorsal neural tube along the entire length of the neuraxis, as well as in the floor plate at the brain but not spinal cord levels. At the midbrain and rostral hindbrain levels, C-Lmx1 is heavily expressed. Here, in addition to expression in the dorsal neural tube and floor plate, it is expressed in the lateral walls of the neural tube, with the exception of the levels of rhombomeres 2 and 4. C-Lmx1 is also expressed in several other discrete domains during and shortly after neurulation, including the prechordal plate and rostral head mesenchyme, foregut endoderm, otic placode and vesicle, dorsal somitic mesoderm, midline endoderm at the level of the caudal spinal cord, mesonephroi and limb bud mesoderm.

Animals↗
PubMed1999

Region-specific cell clones in the developing spinal cord of the zebrafish.

To analyse the proliferative abilities of cells within particular regions of the zebrafish neural plate, injections of fluorescein-dextran were made into single cells at either medial or intermediary positions in the neural plate region of two-somite stage embryos. The resulting cell clones were analysed in 3. 5-day-old embryos. Clones with similar compositions were found among those derived from injections in both regions, and these were grouped into classes. 78 clones 29 obtained following injections in the medial region, and 22 of 59 cell clones derived from injections in the intermediary region, were classifiable into 9 and 10 different classes, respectively, each comprising a variable number of clones. Several identified cell types, as well as each of the clone classes themselves, were specific for the regions of the neural plate from which they derived, i.e. they were not represented among the clones derived from the other region. These results suggest that the composition of the lineages derived from particular cells is constant in different animals.

Animals↗
PubMed1991

Patterns of neurepithelial cell rearrangement during avian neurulation are determined prior to notochordal inductive interactions.

In the epiblast of elongating primitive-streak-stage avian embryos, MHP cells--short wedge-shaped neurepithelial cells contained within the median hinge point of the bending neural plate--arise from the midline prenodal and nodal area, whereas L cells--tall spindle-shaped neurepithelial cells constituting the lateral neural plate--arise from paired areas flanking the cranial primitive streak. These characteristic differences in neurepithelial cell shape are acquired as a result of inductive interactions with the notochord. Both MHP and L cells undergo extensive rearrangement (intercalation) during shaping and bending of the neural plate, but their pattern of rearrangement differs. MHP cells intercalate with other MHP cells and the population always spans the midline, whereas L cells intercalate with other L cells, remaining in bulk lateral to the midline. The following experiment was performed to establish whether these distinctive rearrangement patterns are determined prior to notochordal inductive interactions. Quail prospective MHP and L cells were transplanted isochronically and heterotopically to chick host blastoderms at stages prior to formation of the notochord (to wit, prospective MHP cells were transplanted into prospective L cell territory and vice versa) and the distribution, fate, and morphological characteristics of grafted cells were determined in chimeras collected 24 hr later. Our results demonstrate that heterotopic MHP and L cells do not adopt the rearrangement pattern characteristic of their new site; rather, they change their position so that grafted MHP cells intermix with MHP cells of the host and grafted L cells intermix with L cells of the host. Thus, patterns of neurepithelial cell rearrangement are determined prior to notochordal inductive interactions. When and how this determination occurs are topics for further studies.

Animals↗
PubMed1998

A simple molecular model of neurulation.

A molecular model for the morphogenesis of the central nervous system is built and solved by computer. The formalism rests on molecular-biological data gathered from insects and vertebrates during neural differentiation and neuronal fate specification. Two genetic, hierarchically organized switches are introduced, one associated with f1p4al tissue formation, and the other with neuronal specification. The model switches evolve in time, setting up very similar "prepatterns" of genetic activity in both insects and vertebrates, as observed experimentally. We introduce the hypothesis that cell adhesion and motion are regulated by the switches. If cell motion is turned on by the neural switch, the whole neural tissue (neural plate) thickens, buckles, and folds, ultimately creating a closed neural tube (primary neurulation). When mitoses are more frequent in neural plate tissue, ingression of a neural cell mass takes place instead (secondary neurulation). If cell motions are controlled by the neuronal switch, rather than by the neural one, the differentiation of isolated neuroblasts is observed, which delaminate individually (as in insect neural cord formation). The model thus displays the three major known patterns of neurogenesis; the transition between the vertebrate and insect cases is predicted to result from changes in genetic regulation downstream of the switch genes, and affecting cell adhesion and motility properties. Little is known experimentally about the concerned pathways: their importance as a fruitful area for future investigation is emphasized by our theoretical results.

Animals↗
PubMed1986

Axolotl retina and lens development: mutual tissue stimulation and autonomous failure in the eyeless mutant retina.

During eye development in the axolotl (Ambystoma mexicanum Shaw), morphogenetic movements bring together tissues from head epidermis, neuroectoderm and neural crest. The stages 0 to 14 of axolotl eye development were expanded from Rabl's (1898) stages 1 to 10 and correlated with Harrison's (1969) stages. At the onset of neurulation (stage 13 of Harrison), the head epidermis is already determined to form skin, and the neuroectoderm is committed to form brain, because these tissues develop autonomously in 60% Leibovitz L-15 culture medium. However, a sequence of mutual tissue interactions is necessary to stimulate eye development. When head epidermis and neuroectoderm were cocultured, eyes developed, containing retinas with photoreceptors (stage 8) and lenses with secondary lens fibres (stage 8). The first event needed in this case appears to be the secretion of a growth factor from the head epidermis which stimulates retina development from the neuroectoderm. When neuroectoderm cultures were exposed to nondialysable extracts (30 micrograms ml-1) of an adult epidermis derivative, the bovine cornea, pigmented retinas (stage 6) and at higher concentrations (3000 micrograms ml-1) neural retinas developed (stage 6). In turn, lens formation is stimulated in the head epidermis by a retina-derived growth factor. A mutation that causes adult eyelessness (e eyeless, nonlethal, recessive) affects the earliest event in eye development (stage 1a), while a mutation that causes arrest of eye development (mi microphthalmic, lethal, recessive) acts in a later event (stage 8). Two possibilities have been considered in the case of mutation e: either the head epidermis does not secrete sufficient amounts of active growth factor, or the presumptive retina itself is defective. The latter statement turned out to be correct, because mutant e neural plates rarely developed early retina stages (stage 5) in organ culture when combined with wild-type head epidermis. On the other hand, wild-type neural plates formed advanced retinas (stage 8) in all cases when combined with mutant e head epidermis. As expected, no retina or lens developed when both neural plate and head epidermis were from mutant e donors. The heterozygous presence of genes e and r (renal insufficiency, lethal, recessive) produces duplications of the presumptive retina at the optic stalk. This observation is consistent with the notion that the mutation e, assisted by the r locus, causes a primary failure in the presumptive retinal region.

Ambystoma↗
PubMed2005

Positioning of the midbrain-hindbrain boundary organizer through global posteriorization of the neuroectoderm mediated by Wnt8 signaling.

The organizing center located at the midbrain-hindbrain boundary (MHB) patterns the midbrain and hindbrain primordia of the neural plate. Studies in several vertebrates showed that the interface between cells expressing Otx and Gbx transcription factors marks the location in the neural plate where the organizer forms, but it is unclear how this location is set up. Using mutant analyses and shield ablation experiments in zebrafish, we find that axial mesendoderm, as a candidate tissue, has only a minor role in positioning the MHB. Instead, the blastoderm margin of the gastrula embryo acts as a source of signal(s) involved in this process. We demonstrate that positioning of the MHB organizer is tightly linked to overall neuroectodermal posteriorization, and specifically depends on Wnt8 signaling emanating from lateral mesendodermal precursors. Wnt8 is required for the initial subdivision of the neuroectoderm, including onset of posterior gbx1 expression and establishment of the posterior border of otx2 expression. Cell transplantation experiments further show that Wnt8 signaling acts directly and non-cell-autonomously. Consistent with these findings, a GFP-Wnt8 fusion protein travels from donor cells through early neural plate tissue. Our findings argue that graded Wnt8 activity mediates overall neuroectodermal posteriorization and thus determines the location of the MHB organizer.

Animals↗
PubMed1994

Normal neurulation in amphibians.

How does cell behaviour accomplish neurulation in amphibian embryos? During neurulation, the neural plate (while preserving the same volume) doubles its length, triples its thickness, narrows 10-fold, greatly decreases its surface and rolls into a tube. Cells that compose the neural plate produce these changes in three ways. They change shape, change neighbours and attempt to crawl beneath the contiguous epidermis. Plate width, length and area are decreased and the plate thickens when apical surfaces of plate cells contract radially, but plate length increases and width is further decreased when cells reposition themselves and collect along plate boundaries. Contraction of the apical surfaces of plate cells also helps roll the plate into a tube. Poisson buckling resulting from elongation of plate borders may contribute bending forces that help tube formation. The main folding force in tube formation is a rolling moment toward the midline produced by neural plate cells attempting to crawl beneath the contiguous epidermis. Experiments, observations and computer simulations support these assertions, reveal the organization of cell behaviour and implicate contraction of actin filaments as the main source of the necessary forces.

Amphibians↗
PubMed2004

Role of BMP signaling and the homeoprotein Iroquois in the specification of the cranial placodal field.

Different types of placodes originate at the anterior border of the neural plate but it is still an unresolved question whether individual placodes arise as distinct ectodermal specializations in situ or whether all or a subset of the placodes originate from a common preplacodal field. We have analyzed the expression and function of the homeoprotein Iro1 in Xenopus and zebrafish embryos, and we have compared its expression with several preplacodal and placodal markers. Our results indicate that the iro1 genes are expressed in the preplacodal region, being one of the earliest markers for this area. We show that an interaction between the neural plate and the epidermis is able to induce the expression of several preplacodal markers, including Xiro1, by a similar mechanism to that previously shown for neural crest induction. In addition, we analyzed the role of BMP in the specification of the preplacodal field by studying the expression of the preplacodal markers Six1, Xiro1, and several specific placodal markers. We experimentally modified the level of BMP activity by three different methods. First, we implanted beads soaked with noggin in early neurula stage Xenopus embryos; second, we injected the mRNA that encodes a dominant negative of the BMP receptor into Xenopus and zebrafish embryos; and third, we grafted cells expressing chordin into zebrafish embryos. The results obtained using all three methods show that a reduction in the level of BMP activity leads to an expansion of the preplacodal and placodal region similar to what has been described for neural crest regions. By using conditional constructs of Xiro1, we performed gain and loss of function experiments. We show that Xiro1 play an important role in the specification of both the preplacodal field as well as individual placodes. We have also used inducible dominant negative and activator constructs of Notch signaling components to analyze the role of these factors on placodal development. Our results indicate that the a precise level of BMP activity is required to induce the neural plate border, including placodes and neural crest cells, that in this border the iro1 gene is activated, and that this activation is required for the specification of the placodes.

Animals↗
PubMedDate not supplied

Histologic findings of disc, end plate and neural elements after coblation of nucleus pulposus: an experimental nucleoplasty study.

BACKGROUND CONTEXT: Partial removal of the nucleus has been shown to decompress herniated discs, relieving pressure on nerve roots and, in some cases, offering relief from disc pain. The nucleoplasty technique builds on earlier surgical approaches that helped validate the strategy of intranuclear tissue removal. Nucleoplasty, a new minimally invasive procedure using patented coblation technology, combines coagulation and ablation for partial removal of the nucleus pulposus to decompress the disc. PURPOSE: To determine if histologic changes of the intervertebral discs and surrounding tissues occur after nucleoplasty. STUDY DESIGN: A light microscopic study of intervertebral disc and adjacent neural tissues after disc decompression by nucleoplasty in pig cadavers. METHODS: Light microscopy was used to examine disc and neural tissues in two pig cadaveric specimens (T12 to sacrum). Nucleoplasty was performed by 1) advancing a radiofrequency wand to a predetermined depth in the disc (ablation), and 2) withdrawing the wand to the starting point (coagulation). Discs and adjacent tissues were removed from treated and nontreated segments, and examined under light microscopy. RESULTS: Histologic examination revealed no evidence of direct mechanical or thermal damage to the surrounding tissues. There was clear evidence of coblation channels with clean coagulation borders of the nucleus pulposus. Normal histologic findings of the annulus and end plate, with normal neural elements of the spinal cord and nerve roots at the level of the procedure, were observed. CONCLUSIONS: The histologic findings of this study suggest that the nucleoplasty achieves volumetric removal of target disc tissue without overt thermal or structural damage to the adjacent tissues. Further studies in live animals will be needed to assess the effects of nucleoplasty on the annulus, end plate and neural tissues under physiologic conditions, including assessment of cell viability.

Animals↗
PubMed1988

Cytoarchitectonic investigation of the rat spinal cord following ethylnitrosourea administration at different developmental stages.

We examined the histological findings and cytoarchitectonic alterations in the rat spinal cord following matrix cell degeneration caused at different developmental stages, from neural plate formation through neuroblast generation. Ethylnitrosourea (ENU) 20 mg/kg body weight was administered transplacentally to the fetuses on the 10th embryonic day (E10) to 14th. The observations were made until the 21st postnatal day. Normally, mitoses were present scatteredly in the matrix cell layer of the neural plate or neural tube on E10 or E11, and gradually restricted to the dorsal portion of the alar plate as development occurred. The localization and number of degenerative cells as well as the site and degree of neuronal decrease in the completed dysgenetic spinal cord seemed to correlate with the topography and frequency of the mitoses in the matrix cell layer at the time of ENU administration. Disorder in the pattern of cytoarchitecture of neurons was not observed. The degree of hypoplasia of the white matter was proportional to the intensity of decrease of the spinal neurons. Aberrant myelinated fibers were not seen. No reactive gliosis, fibrosis or abnormal vascularization was observed at any time.

Animals↗
PubMed2006

Neural induction in Xenopus requires inhibition of Wnt-beta-catenin signaling.

Canonical Wnt signals have been implicated in multiple events during early embryogenesis, including primary axis formation, neural crest induction, and A-P patterning of the neural plate. The mechanisms by which Wnt signals can direct distinct fates in cell types that are closely linked both temporally and spatially remains poorly understood. However, recent work has suggested that the downstream transcriptional mediators of this pathway, Lef/Tcf family DNA binding proteins, may confer distinct outcomes on these signals in some cellular contexts. In this study, we first examined whether inhibitory mutants of XTcf3 and XLef1 might block distinct Wnt-dependent signaling events during the diversification of cell fates in the early embryonic ectoderm. We found that a Wnt-unresponsive mutant of XTcf3 potently blocks neural crest formation, whereas an analogous mutant of XLef1 does not, and that the difference in activity mapped to the C-terminus of the proteins. Significantly, the inhibitory XTcf3 mutant also blocked expression of markers of anterior-most cell types, including cement gland and sensory placodes, indicating that Wnt signals are required for rostral as well as caudal ectodermal fates. Unexpectedly, we also found that blocking canonical Wnt signals in the ectoderm, using the inhibitory XTcf3 mutant or by other means, dramatically expanded the size of the neural plate, as evidenced by the increased expression of early pan-neural markers such as Sox3 and Nrp1. Conversely, we find that upregulation of canonical Wnt signals interferes with the induction of the neural plate, and this activity can be separated experimentally from Wnt-mediated neural crest induction. Together these findings provide important and novel insights into the role of canonical Wnt signals during the patterning of vertebrate ectoderm and indicate that Wnt inhibition plays a central role in the process of neural induction.

Animals↗