Longitudinal organization of the anterior neural plate and neural tube

Development ◽  
1995 ◽  
Vol 121 (12) ◽  
pp. 3923-3933 ◽  
Author(s):  
K. Shimamura ◽  
D.J. Hartigan ◽  
S. Martinez ◽  
L. Puelles ◽  
J.L. Rubenstein
Keyword(s):  
Sonic Hedgehog ◽  
Neural Tube ◽  
Longitudinal Axis ◽  
Neural Plate ◽  
Molecular Properties ◽  
Spatially Correlated ◽  
Longitudinal Axon ◽  
Embryonic Cns ◽  
Anterior Neural Plate ◽  
Anterior Posterior

Over the last century, several morphological models of forebrain organization have been proposed that hypothesize alternative topological solutions for the relationships of the histogenic primordia. Central to all of these models are their definitions of the longitudinal axis and the longitudinal organization of the neural plate and neural tube. To understand the longitudinal organization of the anterior brain, we have sought to identify molecular properties that are continuous along the entire longitudinal axis of the embryonic CNS. In this essay, we describe studies of the expression of several genes in the mouse between 7.5 (presomite stage) and 10.5 days post coitum (dpc) that provide evidence for the trajectory of the anterior-posterior axis and the longitudinal organization of the anterior CNS. Specifically, we report that the expression of noggin, sonic hedgehog and Nkx-2.2 define longitudinal columns of cells that are present along the entire CNS axis. Within the forebrain, the expression of these genes, as well as that of Nkx-2.1 and BF-1, are in distinct longitudinal regions in the neural plate and tube. We demonstrate that the earliest longitudinal axon pathways of the forebrain are spatially correlated with the longitudinal domain defined by Nkx-2.2. Finally, expression of the former genes, and Otx-1 and Emx-2, suggests that the cephalic neural plate is organized into molecularly distinct domains delimited by longitudinal and transverse borders; these results provide a foundation for defining the mechanisms that pattern the neural plate.

Inductive interactions direct early regionalization of the mouse forebrain

Development ◽  
1997 ◽  
Vol 124 (14) ◽  
pp. 2709-2718 ◽  
Author(s):  
K. Shimamura ◽  
J.L. Rubenstein
Keyword(s):  
Sonic Hedgehog ◽  
Bone Morphogenetic Proteins ◽  
Molecular Mechanisms ◽  
Neural Plate ◽  
Gene Encoding ◽  
Prechordal Plate ◽  
Optic Vesicles ◽  
The Central Nervous System ◽  
Anterior Neural Plate ◽  
Anterior Posterior

The cellular and molecular mechanisms that regulate regional specification of the forebrain are largely unknown. We studied the expression of transcription factors in neural plate explants to identify tissues, and the molecules produced by these tissues, that regulate medial-lateral and local patterning of the prosencephalic neural plate. Molecular properties of the medial neural plate are regulated by the prechordal plate perhaps through the action of Sonic Hedgehog. By contrast, gene expression in the lateral neural plate is regulated by non-neural ectoderm and bone morphogenetic proteins. This suggests that the forebrain employs the same medial-lateral (ventral-dorsal) patterning mechanisms present in the rest of the central nervous system. We have also found that the anterior neural ridge regulates patterning of the anterior neural plate, perhaps through a mechanism that is distinct from those that regulate general medial-lateral patterning. The anterior neural ridge is essential for expression of BF1, a gene encoding a transcription factor required for regionalization and growth of the telencephalic and optic vesicles. In addition, the anterior neural ridge expresses Fgf8, and recombinant FGF8 protein is capable of inducing BF1, suggesting that FGF8 regulates the development of anterolateral neural plate derivatives. Furthermore, we provide evidence that the neural plate is subdivided into distinct anterior-posterior domains that have different responses to the inductive signals from the prechordal plate, Sonic Hedgehog, the anterior neural ridge and FGF8. In sum, these results suggest that regionalization of the forebrain primordia is established by several distinct patterning mechanisms: (1) anterior-posterior patterning creates transverse zones with differential competence within the neural plate, (2) patterning along the medial-lateral axis generates longitudinally aligned domains and (3) local inductive interactions, such as a signal(s) from the anterior neural ridge, further define the regional organization.

scholarly journals Hallmarks of primary neurulation are conserved in the zebrafish forebrain

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Jonathan M. Werner ◽  
Maraki Y. Negesse ◽  
Dominique L. Brooks ◽  
Allyson R. Caldwell ◽  
Jafira M. Johnson ◽  
...  
Keyword(s):  
Neural Tube ◽  
Time Lapse ◽  
Neural Plate ◽  
Neural Tube Closure ◽  
Developmental Studies ◽  
Underlying Causes ◽  
The Central Nervous System ◽  
Resolution Imaging ◽  
Fold Formation ◽  
Anterior Neural Plate

AbstractPrimary neurulation is the process by which the neural tube, the central nervous system precursor, is formed from the neural plate. Incomplete neural tube closure occurs frequently, yet underlying causes remain poorly understood. Developmental studies in amniotes and amphibians have identified hingepoint and neural fold formation as key morphogenetic events and hallmarks of primary neurulation, the disruption of which causes neural tube defects. In contrast, the mode of neurulation in teleosts has remained highly debated. Teleosts are thought to have evolved a unique mode of neurulation, whereby the neural plate infolds in absence of hingepoints and neural folds, at least in the hindbrain/trunk where it has been studied. Using high-resolution imaging and time-lapse microscopy, we show here the presence of these morphological landmarks in the zebrafish anterior neural plate. These results reveal similarities between neurulation in teleosts and other vertebrates and hence the suitability of zebrafish to understand human neurulation.

scholarly journals Effects of Shh and Noggin on neural crest formation demonstrate that BMP is required in the neural tube but not ectoderm

Development ◽  
1998 ◽  
Vol 125 (24) ◽  
pp. 4919-4930 ◽  
Author(s):  
M.A. Selleck ◽  
M.I. Garcia-Castro ◽  
K.B. Artinger ◽  
M. Bronner-Fraser
Keyword(s):  
Neural Crest ◽  
Sonic Hedgehog ◽  
Neural Tube ◽  
Neural Crest Cells ◽  
Neural Plate ◽  
Bmp Signaling ◽  
Neural Tube Closure ◽  
Dorsal Neural Tube ◽  
Neural Ectoderm ◽  
Tube Closure

To define the timing of neural crest formation, we challenged the fate of presumptive neural crest cells by grafting notochords, Sonic Hedgehog- (Shh) or Noggin-secreting cells at different stages of neurulation in chick embryos. Notochords or Shh-secreting cells are able to prevent neural crest formation at open neural plate levels, as assayed by DiI-labeling and expression of the transcription factor, Slug, suggesting that neural crest cells are not committed to their fate at this time. In contrast, the BMP signaling antagonist, Noggin, does not repress neural crest formation at the open neural plate stage, but does so if injected into the lumen of the closing neural tube. The period of Noggin sensitivity corresponds to the time when BMPs are expressed in the dorsal neural tube but are down-regulated in the non-neural ectoderm. To confirm the timing of neural crest formation, Shh or Noggin were added to neural folds at defined times in culture. Shh inhibits neural crest production at early stages (0-5 hours in culture), whereas Noggin exerts an effect on neural crest production only later (5-10 hours in culture). Our results suggest three phases of neurulation that relate to neural crest formation: (1) an initial BMP-independent phase that can be prevented by Shh-mediated signals from the notochord; (2) an intermediate BMP-dependent phase around the time of neural tube closure, when BMP-4 is expressed in the dorsal neural tube; and (3) a later pre-migratory phase which is refractory to exogenous Shh and Noggin.

Sonic hedgehog and the molecular regulation of mouse neural tube closure

Development ◽  
2002 ◽  
Vol 129 (10) ◽  
pp. 2507-2517 ◽  
Author(s):  
Patricia Ybot-Gonzalez ◽  
Patricia Cogram ◽  
Dianne Gerrelli ◽  
Andrew J. Copp
Keyword(s):  
Sonic Hedgehog ◽  
Neural Tube ◽  
Hedgehog Signaling ◽  
Neural Plate ◽  
Neural Tube Closure ◽  
Molecular Regulation ◽  
Sonic Hedgehog Signaling ◽  
Surface Ectoderm ◽  
Necessary And Sufficient ◽  
Tube Closure

Neural tube closure is a fundamental embryonic event whose molecular regulation is poorly understood. As mouse neurulation progresses along the spinal axis, there is a shift from midline neural plate bending to dorsolateral bending. Here, we show that midline bending is not essential for spinal closure since, in its absence, the neural tube can close by a ‘default’ mechanism involving dorsolateral bending, even at upper spinal levels. Midline and dorsolateral bending are regulated by mutually antagonistic signals from the notochord and surface ectoderm. Notochordal signaling induces midline bending and simultaneously inhibits dorsolateral bending. Sonic hedgehog is both necessary and sufficient to inhibit dorsolateral bending, but is neither necessary nor sufficient to induce midline bending, which seems likely to be regulated by another notochordal factor. Attachment of surface ectoderm cells to the neural plate is required for dorsolateral bending, which ensures neural tube closure in the absence of sonic hedgehog signaling.

Gene activation during early stages of lens induction in Xenopus

Development ◽  
1998 ◽  
Vol 125 (17) ◽  
pp. 3509-3519 ◽  
Author(s):  
C.A. Zygar ◽  
T.L. Cook ◽  
R.M. Grainger
Keyword(s):  
Neural Tube ◽  
Gene Activation ◽  
Neural Plate ◽  
Neural Tube Closure ◽  
Gene Products ◽  
Optic Vesicle ◽  
Determination Process ◽  
Tightly Coupled ◽  
Anterior Neural Plate ◽  
Tube Closure

Several stages in the lens determination process have been defined, though it is not known which gene products control these events. At mid-gastrula stages in Xenopus, ectoderm is transiently competent to respond to lens-inducing signals. Between late gastrula and neural tube stages, the presumptive lens ectoderm acquires a lens-forming bias, becomes specified to form lens and begins differentiation. Several genes have been identified, either by expression pattern, mutant phenotype or involvement in crystallin gene regulation, that may play a role in lens bias and specification, and we focus on these roles here. Fate mapping shows that the transcriptional regulators Otx-2, Pax-6 and Sox-3 are expressed in the presumptive lens ectoderm prior to lens differentiation. Otx-2 appears first, followed by Pax-6, during the stages of lens bias (late neural plate stages); expression of Sox-3 follows neural tube closure and lens specification. We also demonstrate the expression of these genes in competent ectoderm transplanted to the lens-forming region. Expression of these genes is maintained or activated preferentially in ectoderm in response to the anterior head environment. Finally, we examined activation of these genes in response to early and late lens-inducing signals. Activation of Otx-2, Pax-6 and Sox-3 in competent ectoderm occurs in response to the early inducing tissue, the anterior neural plate. Since Sox-3 is activated following neural tube closure, we tested its dependence on the later inducing tissue, the optic vesicle, which contacts lens ectoderm at this stage. Sox-3 is not expressed in lens ectoderm, nor does a lens form, when the optic vesicle anlage is removed at late neural plate stages. Expression of these genes demarcates patterning events preceding differentiation and is tightly coupled to particular phases of lens induction.

Expression of Pax-3 is initiated in the early neural plate by posteriorizing signals produced by the organizer and by posterior non-axial mesoderm

Development ◽  
1997 ◽  
Vol 124 (10) ◽  
pp. 2075-2085 ◽  
Author(s):  
A.G. Bang ◽  
N. Papalopulu ◽  
C. Kintner ◽  
M.D. Goulding
Keyword(s):  
Retinoic Acid ◽  
Neural Tube ◽  
Retinoic Acid Receptor ◽  
Homeobox Gene ◽  
Neural Plate ◽  
Transcript Expression ◽  
Fgf Receptor ◽  
Acid Receptor ◽  
Anterior Neural Plate ◽  
Lines Of Evidence

Pax-3 is a paired-type homeobox gene that is specifically expressed in the dorsal and posterior neural tube. We have investigated inductive interactions that initiate Pax-3 transcript expression in the early neural plate. We present several lines of evidence that support a model where Pax-3 expression is initiated by signals that posteriorize the neuraxis, and then secondarily restricted dorsally in response to dorsal-ventral patterning signals. First, in chick and Xenopus gastrulae the onset of Pax-3 expression occurs in regions fated to become posterior CNS. Second, Hensen's node and posterior non-axial mesoderm which underlies the neural plate induce Pax-3 expression when combined with presumptive anterior neural plate explants. In contrast, presumptive anterior neural plate explants are not competent to express Pax-3 in response to dorsalizing signals from epidermal-ectoderm. Third, in a heterospecies explant recombinant assay with Xenopus animal caps (ectoderm) as a responding tissue, late, but not early, Hensen's node induces Pax-3 expression. Chick posterior non-axial mesoderm also induces Pax-3, provided that the animal caps are neuralized by treatment with noggin. Finally we show that the putative posteriorizing factors, retinoic acid and bFGF, induce Pax-3 in neuralized animal caps. However, blocking experiments with a dominant-inhibitory FGF receptor and a dominant-inhibitory retinoic acid receptor suggest that Pax-3 inductive activities arising from Hensen's node and posterior non-axial mesoderm do not strictly depend on FGF or retinoic acid.

Isolation of the mouse Hox-2.9 gene; analysis of embryonic expression suggests that positional information along the anterior-posterior axis is specified by mesoderm

Development ◽  
1990 ◽  
Vol 110 (2) ◽  
pp. 589-607 ◽  
Author(s):  
M.A. Frohman ◽  
M. Boyle ◽  
G.R. Martin
Keyword(s):  
Gene Expression ◽  
Neural Tube ◽  
Expression Patterns ◽  
Positional Information ◽  
Branchial Arch ◽  
Neural Plate ◽  
Specific Gene ◽  
Second Phase ◽  
Anterior Posterior ◽  
Rhombomere 4

It is rapidly becoming accepted that the vertebrate neural tube, in particular the hindbrain, develops into a segmented structure. After segment formation, cells in the neural tube do not cross segmental boundaries, and segment-specific gene expression is observed. However, it is not known what positional cues instruct the neural tube to express genes in this restricted manner. We have cloned a murine homeobox-containing gene, Hox-2.9, whose expression in the neural tube at E9.5 is restricted to a segment of the hindbrain known as rhombomere 4. A study of its expression pattern earlier in development revealed that prior to the start of neurulation (E7.5) Hox-2.9 is expressed within a posterior to the embryonic mesoderm that will participate in hindbrain formation. With the onset of neurulation, expression then becomes detectable in the neural plate as well, but only in the part that overlies the Hox-2.9-expressing mesoderm; it is not detected in the more anterior neuroectoderm that will form the future midbrain and forebrain. On the basis of these findings, we propose that the mesoderm is providing cues that serve to instruct the overlying neuroectoderm with respect to its position along the anteroposterior axis and that Hox-2.9 participates in or reflects this process. As neurulation continues and individual segments form, a second phase of expression is detected in the neural tube in which high levels of Hox-2.9 transcripts become restricted to rhombomere 4. Hox-2.9 expression is also detected in the developing branchial arch units of the hindbrain region, in a pattern that suggests to us that here, too, mesoderm is providing a localized signal that induces Hox-2.9 expression, in this case in endoderm of the pharynx and in superficial ectoderm. In general, we interpret the expression patterns of Hox-2.9 in the hindbrain region as suggesting that the specific mechanisms of pattern formation in mammals are fundamentally similar to those of amphibians and avians - i.e. anteroposterior positional information is acquired by mesoderm, mesoderm induces positional values within (neuro-) ectoderm and endoderm, and both events occur within a restricted window of time.

Gli1 is a target of Sonic hedgehog that induces ventral neural tube development

Development ◽  
1997 ◽  
Vol 124 (13) ◽  
pp. 2537-2552 ◽  
Author(s):  
J. Lee ◽  
K.A. Platt ◽  
P. Censullo ◽  
A. Ruiz i Altaba
Keyword(s):  
Sonic Hedgehog ◽  
Neural Tube ◽  
Transcriptional Regulator ◽  
Floor Plate ◽  
Neural Plate ◽  
Mouse Embryos ◽  
Human Glioma ◽  
Cubitus Interruptus ◽  
Ventral Neural Tube ◽  
Neural Tube Development

The vertebrate zinc finger genes of the Gli family are homologs of the Drosophila gene cubitus interruptus. In frog embryos, Gli1 is expressed transiently in the prospective floor plate during gastrulation and in cells lateral to the midline during late gastrula and neurula stages. In contrast, Gli2 and Gli3 are absent from the neural plate midline with Gli2 expressed widely and Gli3 in a graded fashion with highest levels in lateral regions. In mouse embryos, the three Gli genes show a similar pattern of expression in the neural tube but are coexpressed throughout the early neural plate. Because Gli1 is the only Gli gene expressed in prospective floor plate cells of frog embryos, we have investigated a possible involvement of this gene in ventral neural tube development. Here we show that Shh signaling activates Gli1 transcription and that widespread expression of endogenous frog or human glioma Gli1, but not Gli3, in developing frog embryos results in the ectopic differentiation of floor plate cells and ventral neurons within the neural tube. Floor-plate-inducing ability is retained when cytoplasmic Gli1 proteins are forced into the nucleus or are fused to the VP16 transactivating domain. Thus, our results identify Gli1 as a midline target of Shh and suggest that it mediates the induction of floor plate cells and ventral neurons by Shh acting as a transcriptional regulator.

Early subdivisions in the neural plate define distinct competence for inductive signals

Development ◽  
2002 ◽  
Vol 129 (1) ◽  
pp. 83-93 ◽  
Author(s):  
Daisuke Kobayashi ◽  
Makoto Kobayashi ◽  
Ken Matsumoto ◽  
Toshihiko Ogura ◽  
Masato Nakafuku ◽  
...  
Keyword(s):  
Sonic Hedgehog ◽  
Optic Tectum ◽  
Neural Plate ◽  
Specific Response ◽  
Embryonic Brain ◽  
Fgf Receptor ◽  
Fibroblast Growth Factor 8 ◽  
Equivalent Potential ◽  
The Brain ◽  
Anterior Posterior

Regionalization of the embryonic brain is achieved through multi-step processes that operate sequentially and/or simultaneously. Localized sources of various signaling molecules act as organizing centers that pattern neighboring fields to create molecularly distinct domains. We investigated the mechanisms underlying the regionally distinct competence for two such organizing signals, Fibroblast growth factor 8 (Fgf8) and Sonic hedgehog (Shh), using chick embryos. First, we demonstrated that FGF receptor 1 (Fgfr1) and Fgfr3, expressed differentially in the developing brain, possess an equivalent potential to induce the regionally distinct Fgf8-responsive genes, depending on the anterior-posterior dimension of the brain. Next we found that homeodomain transcription factors Six3 and Irx3 can alter the regional responses to both Fgf8 and Shh in the forebrain. Six3 confers the ability to express Bf1, a gene essential for the telencephalon and eye development, and Nkx2.1, which is required for development of the hypothalamus. In contrast, Irx3 confers the ability to express En2 and Nkx6.1 in response to Fgf8 and Shh, respectively. Furthermore, an alteration in the region-specific response to Fgf8 upon misexpression of Irx3 resulted in transformation of diencephalic and possibly telencephalic tissues into the optic tectum. Finally, we demonstrated that Six3 and Irx3 can mutually repress their expression, which may contribute to the establishment of their complementary expression domains in the neural plate. These repressive interactions are specific, as Six3 did not repress Gbx2, and Irx3 did not disturb Otx2 expression. These findings provide evidence that the early embryonic forebrain is demarcated into two domains with distinct genetic programs, which argues against the authentic telen-diencephalic subdivision.

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