scholarly journals Differential patterning of ventral midline cells by axial mesoderm is regulated by BMP7 and chordin

Development ◽  
1999 ◽  
Vol 126 (2) ◽  
pp. 397-408 ◽  
Author(s):  
K. Dale ◽  
N. Sattar ◽  
J. Heemskerk ◽  
J.D. Clarke ◽  
M. Placzek ◽  
...  
Keyword(s):  
Sonic Hedgehog ◽  
Floor Plate ◽  
Neural Plate ◽  
Ventral Midline ◽  
Molecular Events ◽  
Morphogenetic Protein ◽  
Explant Cultures ◽  
Prechordal Mesoderm ◽  
Midline Cells ◽  
Bmp Antagonist

Ventral midline cells in the neural tube have distinct properties at different rostrocaudal levels, apparently in response to differential signalling by axial mesoderm. Floor plate cells are induced by sonic hedgehog (SHH) secreted from the notochord whereas ventral midline cells of the rostral diencephalon (RDVM cells) appear to be induced by the dual actions of SHH and bone morphogenetic protein 7 (BMP7) from prechordal mesoderm. We have examined the cellular and molecular events that govern the program of differentiation of RDVM cells under the influence of the axial mesoderm. By fate mapping, we show that prospective RDVM cells migrate rostrally within the neural plate, passing over rostral notochord before establishing register with prechordal mesoderm at stage 7. Despite the co-expression of SHH and BMP7 by rostral notochord, prospective RDVM cells appear to be specified initially as caudal ventral midline neurectodermal cells and to acquire RDVM properties only at stage 7. We provide evidence that the signalling properties of axial mesoderm over this period are regulated by the BMP antagonist, chordin. Chordin is expressed throughout the axial mesoderm as it extends, but is downregulated in prechordal mesoderm coincident with the onset of RDVM cell differentiation. Addition of chordin to conjugate explant cultures of prechordal mesoderm and neural tissue prevents the rostralization of ventral midline cells by prechordal mesoderm. Chordin may thus act to refine the patterning of the ventral midline along the rostrocaudal axis.

Direct action of the nodal-related signal cyclops in induction of sonic hedgehog in the ventral midline of the CNS

Development ◽  
2000 ◽  
Vol 127 (18) ◽  
pp. 3889-3897 ◽  
Author(s):  
F. Muller ◽  
S. Albert ◽  
P. Blader ◽  
N. Fischer ◽  
M. Hallonet ◽  
...  
Keyword(s):  
Sonic Hedgehog ◽  
Neural Tube ◽  
Direct Action ◽  
Brain Regions ◽  
Floor Plate ◽  
Ventral Midline ◽  
Signal Transducers ◽  
Step Model ◽  
Ventral Neural Tube ◽  
Differential Responsiveness

The secreted molecule Sonic hedgehog (Shh) is crucial for floor plate and ventral brain development in amniote embryos. In zebrafish, mutations in cyclops (cyc), a gene that encodes a distinct signal related to the TGF(beta) family member Nodal, result in neural tube defects similar to those of shh null mice. cyc mutant embryos display cyclopia and lack floor plate and ventral brain regions, suggesting a role for Cyc in specification of these structures. cyc mutants express shh in the notochord but lack expression of shh in the ventral brain. Here we show that Cyc signalling can act directly on shh expression in neural tissue. Modulation of the Cyc signalling pathway by constitutive activation or inhibition of Smad2 leads to altered shh expression in zebrafish embryos. Ectopic activation of the shh promoter occurs in response to expression of Cyc signal transducers in the chick neural tube. Furthermore an enhancer of the shh gene, which controls ventral neural tube expression, is responsive to Cyc signal transducers. Our data imply that the Nodal related signal Cyc induces shh expression in the ventral neural tube. Based on the differential responsiveness of shh and other neural tube specific genes to Hedgehog and Cyc signalling, a two-step model for the establishment of the ventral midline of the CNS is proposed.

Ventral midline cells are required for the local control of commissural axon guidance in the mouse spinal cord

Development ◽  
1999 ◽  
Vol 126 (16) ◽  
pp. 3649-3659
Author(s):  
M.P. Matise ◽  
M. Lustig ◽  
T. Sakurai ◽  
M. Grumet ◽  
A.L. Joyner
Keyword(s):  
Spinal Cord ◽  
Critical Role ◽  
Floor Plate ◽  
Posterior Commissure ◽  
Ventral Midline ◽  
Mouse Spinal Cord ◽  
Commissural Axons ◽  
Midline Cells

Specialized cells at the midline of the central nervous system have been implicated in controlling axon projections in both invertebrates and vertebrates. To address the requirement for ventral midline cells in providing cues to commissural axons in mice, we have analyzed Gli2 mouse mutants, which lack specifically the floor plate and immediately adjacent interneurons. We show that a Dbx1 enhancer drives tau-lacZ expression in a subpopulation of commissural axons and, using a reporter line generated from this construct, as well as DiI tracing, we find that commissural axons projected to the ventral midline in Gli2(−/−) embryos. Netrin1 mRNA expression was detected in Gli2(−/−) embryos and, although much weaker than in wild-type embryos, was found in a dorsally decreasing gradient. This result demonstrates that while the floor plate can serve as a source of long-range cues for C-axons in vitro, it is not required in vivo for the guidance of commissural axons to the ventral midline in the mouse spinal cord. After reaching the ventral midline, most commissural axons remained clustered in Gli2(−/−) embryos, although some were able to extend longitudinally. Interestingly, some of the longitudinally projecting axons in Gli2(−/−) embryos extended caudally and others rostrally at the ventral midline, in contrast to normal embryos in which virtually all commissural axons turn rostrally after crossing the midline. This finding indicates a critical role for ventral midline cells in regulating the rostral polarity choice made by commissural axons after they cross the midline. In addition, we provide evidence that interactions between commissural axons and floor plate cells are required to modulate the localization of Nr-CAM and TAG-1 proteins on axons at the midline. Finally, we show that the floor plate is not required for the early trajectory of motoneurons or axons of the posterior commissure, whose projections are directed away from the ventral midline in both WT and Gli2(−/−) embryos, although they are less well organized in Gli2(−/−)mutants.

Induction of floor plate differentiation by contact-dependent, homeogenetic signals

Development ◽  
1993 ◽  
Vol 117 (1) ◽  
pp. 205-218 ◽  
Author(s):  
M. Placzek ◽  
T.M. Jessell ◽  
J. Dodd
Keyword(s):  
Axon Guidance ◽  
Neural Tube ◽  
Floor Plate ◽  
Cell Patterning ◽  
Neural Plate ◽  
Neural Cells ◽  
Cellular Mechanisms ◽  
Prechordal Mesoderm ◽  
Specific Antigens ◽  
Inductive Signals

The floor plate is located at the ventral midline of the neural tube and has been implicated in neural cell patterning and axon guidance. To address the cellular mechanisms involved in floor plate differentiation, we have used an assay that monitors the expression of floor-plate-specific antigens in neural plate explants cultured in the presence of inducing tissues. Contact-mediated signals from both the notochord and the floor plate act directly on neural plate cells to induce floor plate differentiation. Floor plate induction is initiated medially by a signal from the notochord, but appears to be propagated to more lateral cells by homeogenetic signals that derive from medial floor plate cells. The response of neural plate cells to inductive signals declines with embryonic age, suggesting that the mediolateral extent of the floor plate is limited by a loss of competence of neural cells. The rostral boundary of the floor plate at the midbrain-forebrain junction appears to result from the lack of inducing activity in prechordal mesoderm and the inability of rostral neural plate cells to respond to inductive signals.

Combinatorial Gli gene function in floor plate and neuronal inductions by Sonic hedgehog

Development ◽  
1998 ◽  
Vol 125 (12) ◽  
pp. 2203-2212 ◽  
Author(s):  
A. Ruiz i Altaba
Keyword(s):  
Motor Neurons ◽  
Positional Information ◽  
Floor Plate ◽  
Neural Plate ◽  
Neural Cells ◽  
Spinal Motor Neurons ◽  
Gli Proteins ◽  
Regulatory Feedback Loop ◽  
Midline Cells ◽  
Definition Of

Within the developing vertebrate nervous system, it is not known how progenitor cells interpret the positional information provided by inducing signals or how the domains in which distinct groups of neural cells differentiate are defined. Gli proteins may be involved in these processes. In the frog neural plate, we have previously shown that the zinc finger transcription factor Gli1 is expressed in midline cells and mediates the effects of Shh inducing floor plate differentiation. In contrast, Gli2 and Gli3 are expressed throughout the neural plate except for the midline. Here, it is shown that Gli3 and Shh repress each other whereas Gli2, like Gli1, is a target of Shh signaling. However, only Gli1 can induce the differentiation of floor plate cells. In addition, Gli2 and Gli3 repress the ectopic induction of floor plate cells by Gli1 in co-injection assays and inhibit endogenous floor plate differentiation. The definition of the floor plate domain, therefore, appears to be defined by the antagonizing activities of Gli2 and Gli3 on Gli1 function. Because both Gli1 and Gli2 are induced by Shh, these results establish a regulatory feedback loop triggered by Shh that restricts floor plate cells to the midline. We have also previously shown that the Gli genes induce neuronal differentiation and here it is shown that there is specificity to the types of neurons the Gli proteins induce. Only Gli1 induces Nkx2.1/TTF-1(+) ventral forebrain neurons. Moreover, Gli2 and Gli3 inhibit their differentiation. In contrast, the differentiation of spinal motor neurons can be induced by the two ventrally expressed Gli genes, Gli1 and Gli2, suggesting that Gli2 directly mediates induction of motor neurons by Shh. In addition, Gli3 inhibits motor neuron differentiation by Gli2. Thus, combinatorial Gli function may pattern the neural tube, integrating positional information and cell type differentiation.

scholarly journals Determination of Neuroepithelial Cell Fate: Induction of the Oligodendrocyte Lineage by Ventral Midline Cells and Sonic Hedgehog

1996 ◽  
Vol 177 (1) ◽  
pp. 30-42 ◽  
Author(s):  
Nigel P. Pringle ◽  
Wei-Ping Yu ◽  
Sarah Guthrie ◽  
Henk Roelink ◽  
Andrew Lumsden ◽  
...  
Keyword(s):  
Cell Fate ◽  
Sonic Hedgehog ◽  
Neuroepithelial Cell ◽  
Ventral Midline ◽  
Midline Cells

scholarly journals Cooperation of BMP7 and SHH in the Induction of Forebrain Ventral Midline Cells by Prechordal Mesoderm

Cell ◽  
1997 ◽  
Vol 90 (2) ◽  
pp. 257-269 ◽  
Author(s):  
J.Kim Dale ◽  
Christine Vesque ◽  
Thierry J Lints ◽  
T.Kuber Sampath ◽  
Andrew Furley ◽  
...  
Keyword(s):  
Ventral Midline ◽  
Prechordal Mesoderm ◽  
Midline Cells

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.

scholarly journals Lithium changes the ectodermal fate of individual frog blastomeres because it causes ectopic neural plate formation

Development ◽  
1989 ◽  
Vol 106 (3) ◽  
pp. 599-610
Author(s):  
S.L. Klein ◽  
S.A. Moody
Keyword(s):  
Neural Plate ◽  
Early Cleavage ◽  
Ventral Midline ◽  
Plate Formation ◽  
Form Part ◽  
Cleavage Stages ◽  
Midline Cells ◽  
The Brain ◽  
Brain Examination ◽  
Developmental Window

Amphibian blastulae that are treated with lithium (Li) develop into embryos that consist almost exclusively of head structures. This dramatic change in embryogenesis may occur either because Li selectively kills trunk progenitors or because Li causes trunk progenitors to become head progenitors. To distinguish between these possibilities, we compared the fates of individual frog blastomeres between Li-treated embryos and normal embryos using lineage tracers. The results demonstrate that Li causes ventral midline cells, which normally populate large amounts of trunk, to produce many head structures, including the brain. Examination of fluorescently labeled clones in living Li-treated gastrulae shows that: (1) the ectodermal members of the clones migrate normally, and chordamesodermal involution begins normally; (2) the chordamesoderm's later involution is altered such that it is confined to the vegetal hemisphere; (3) accordingly, the neural plate forms in the vegetal hemisphere, circumscribing the blastopore, which normally gives rise to the cloaca; and (4) the ectodermal progeny of the ventral midline blastomeres that are near the blastopore populate the brain because they are induced by the stalled chordamesoderm to form part of the ectopic neural plate. These results demonstrate that Li, administered during a short developmental window at early cleavage stages, ultimately alters ectodermal fate because it changes the pattern of chordamesodermal involution during gastrulation, which in turn changes the site of neural plate formation.

Pintallavis, a gene expressed in the organizer and midline cells of frog embryos: involvement in the development of the neural axis

Development ◽  
1992 ◽  
Vol 116 (1) ◽  
pp. 81-93 ◽  
Author(s):  
A. Ruiz i Altaba ◽  
T.M. Jessell
Keyword(s):  
Neural Tube ◽  
Organizer Region ◽  
Cell Types ◽  
Floor Plate ◽  
Neural Cell ◽  
Neural Plate ◽  
Germ Layers ◽  
Fork Head ◽  
Neural Axis ◽  
Midline Cells

We have identified a novel frog gene, Pintallavis (the Catalan for lipstick), that is related to the fly fork head and rat HNF-3 genes. Pintallavis is expressed in the organizer region of gastrula embryos as a direct zygotic response to dorsal mesodermal induction. Subsequently, Pintallavis is expressed in axial midline cells of all three germ layers. In axial mesoderm expression is graded with highest levels posteriorly. Midline neural plate cells that give rise to the floor plate transiently express Pintallavis, apparently in response to induction by the notochord. Overexpression of Pintallavis perturbs the development of the neural axis, suppressing the differentiation of anterior and dorsal neural cell types but causing an expansion of the posterior neural tube. Our results suggest that Pintallavis functions in the induction and patterning of the neural axis.

Anti-apoptotic role of Sonic hedgehog protein at the early stages of nervous system organogenesis

Development ◽  
2001 ◽  
Vol 128 (20) ◽  
pp. 4011-4020 ◽  
Author(s):  
Jean-Baptiste Charrier ◽  
Françoise Lapointe ◽  
Nicole M. Le Douarin ◽  
Marie-Aimée Teillet
Keyword(s):  
Cell Death ◽  
Nervous System ◽  
Chick Embryo ◽  
Sonic Hedgehog ◽  
Neural Tube ◽  
Primitive Streak ◽  
Embryo Cell ◽  
Floor Plate ◽  
Cell Death Program ◽  
Midline Cells

In vertebrates the neural tube, like most of the embryonic organs, shows discreet areas of programmed cell death at several stages during development. In the chick embryo, cell death is dramatically increased in the developing nervous system and other tissues when the midline cells, notochord and floor plate, are prevented from forming by excision of the axial-paraxial hinge (APH), i.e. caudal Hensen’s node and rostral primitive streak, at the 6-somite stage (Charrier, J. B., Teillet, M.-A., Lapointe, F. and Le Douarin, N. M. (1999). Development126, 4771-4783). In this paper we demonstrate that one day after APH excision, when dramatic apoptosis is already present in the neural tube, the latter can be rescued from death by grafting a notochord or a floor plate fragment in its vicinity. The neural tube can also be recovered by transplanting it into a stage-matched chick embryo having one of these structures. In addition, cells engineered to produce Sonic hedgehog protein (SHH) can mimic the effect of the notochord and floor plate cells in in situ grafts and transplantation experiments. SHH can thus counteract a built-in cell death program and thereby contribute to organ morphogenesis, in particular in the central nervous system.

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