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.

Control of dorsoventral pattern in vertebrate neural development: induction and polarizing properties of the floor plate

Development ◽  
1991 ◽  
Vol 113 (Supplement_2) ◽  
pp. 105-122 ◽  
Author(s):  
Marysia Placzek ◽  
Toshiya Yamada ◽  
Marc Tessier-Lavigne ◽  
Thomas Jessell ◽  
Jane Dodd
Keyword(s):  
Neural Tube ◽  
Neural Development ◽  
Cell Types ◽  
Floor Plate ◽  
Neural Cells ◽  
Dorsoventral Patterning ◽  
Cellular Mechanisms ◽  
Cell Position

Distinct classes of neural cells differentiate at specific locations within the embryonic vertebrate nervous system. To define the cellular mechanisms that control the identity and pattern of neural cells we have used a combination of functional assays and antigenic markers to examine the differentiation of cells in the developing spinal cord and hindbrain in vivo and in vitro. Our results suggest that a critical step in the dorsoventral patterning of the embryonic CNS is the differentiation of a specialized group of midline neural cells, termed the floor plate, in response to local inductive signals from the underlying notochord. The floor plate and notochord appear to control the pattern of cell types that appear along the dorsoventral axis of the neural tube. The fate of neuroepithelial cells in the ventral neural tube may be defined by cell position with respect to the ventral midline and controlled by polarizing signals that originate from the floor plate and notochord.

BMP signaling patterns the dorsal and intermediate neural tube via regulation of homeobox and helix-loop-helix transcription factors

Development ◽  
2002 ◽  
Vol 129 (10) ◽  
pp. 2459-2472 ◽  
Author(s):  
John R. Timmer ◽  
Charlotte Wang ◽  
Lee Niswander
Keyword(s):  
Transcription Factors ◽  
Neural Tube ◽  
Transforming Growth Factor ◽  
Cell Types ◽  
Neural Cell ◽  
Bmp Signaling ◽  
Expression Domain ◽  
Cell Identity ◽  
Dorsoventral Axis ◽  
Helix Loop Helix

In the spinal neural tube, populations of neuronal precursors that express a unique combination of transcription factors give rise to specific classes of neurons at precise locations along the dorsoventral axis. Understanding the patterning mechanisms that generate restricted gene expression along the dorsoventral axis is therefore crucial to understanding the creation of diverse neural cell types. Bone morphogenetic proteins (BMPs) and other transforming growth factor β (TGFβ) proteins are expressed by the dorsal-most cells of the neural tube (the roofplate) and surrounding tissues, and evidence indicates that they play a role in assigning cell identity. We have manipulated the level of BMP signaling in the chicken neural tube to show that BMPs provide patterning information to both dorsal and intermediate cells. BMP regulation of the expression boundaries of the homeobox proteins Pax6, Dbx2 and Msx1 generates precursor populations with distinct developmental potentials. Within the resulting populations, thresholds of BMP act to set expression domain boundaries of developmental regulators of the homeobox and basic helix-loop-helix (bHLH) families, ultimately leading to the generation of a diversity of differentiated neural cell types. This evidence strongly suggests that BMPs are the key regulators of dorsal cell identity in the spinal neural tube.

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.

Development of the central nervous system

2013 ◽  
Author(s):  
Martin E. Atkinson
Keyword(s):  
Spinal Cord ◽  
Nervous System ◽  
Neural Tube ◽  
Large Diameter ◽  
Floor Plate ◽  
Neural Plate ◽  
Ependymal Cells ◽  
High Dose ◽  
Neuronal Processes ◽  
Mantle Layer

The early development of the nervous system, the process of neurulation, has already been outlined in Chapter 8 and illustrated in Figure 8.4. To briefly recap, an area of dorsal ectoderm is induced by the underlying notochord to form the neural plate during the third week of development. The lateral edges of the neural plate rise to form the neural folds which eventually fold over and unite in the midline by the end of the fourth week to produce the neural tube. A distinct cell population on the crest of the neural folds, the neural crest, migrates from the forming neural tube to form various structures, including components of the peripheral nervous system. The closed neural tube consists of a large diameter anterior portion that will become the brain and a longer cylindrical posterior section, the future spinal cord. Initially, the neural plate is a single cell layer, but concentric layers of cells can be recognized by the time the neural tube has closed. An inner layer of ependymal cells surrounds the central spinal canal. Neuroblasts, the precursors of neurons, make up the bulk of the neural tube called the mantle layer; this will become the grey matter of the spinal cord. Neuroblasts do not extend processes until they have completed their differentiation. When the cells in a particular location are fully differentiated, the neuronal processes emerging from the neuroblasts form an outer marginal layer which ultimately becomes the white matter of the spinal cord. Figure 19.1B shows that the neural tube changes shape due to proliferation of cells in the mantle layer. This figure also indicates two midline structures in the roof and floor of the tube, known as the roof plate and floor plate. They are important in the determination of the types of neurons that develop from the mantle layer. The floor plate is induced by the expression of a protein product of a gene called sonic hedgehog (SHH) produced by the underlying notochord; the floor plate then expresses the same gene itself. Neuroblasts nearest to the floor plate receive a high dose of SHH protein and respond by differentiating into motor neurons; as seen in Figure 19.1B, these cells group together to form bilateral ventrolateral basal plates.

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.

Regulation of the neural patterning activity of sonic hedgehog by secreted BMP inhibitors expressed by notochord and somites

Development ◽  
2000 ◽  
Vol 127 (22) ◽  
pp. 4855-4866 ◽  
Author(s):  
K.F. Liem ◽  
T.M. Jessell ◽  
J. Briscoe
Keyword(s):  
Neural Tube ◽  
Progenitor Cell ◽  
Cell Types ◽  
Neural Cell ◽  
Bmp Signaling ◽  
Neural Cells ◽  
Cell Identity ◽  
Neuronal Fate ◽  
Ventral Neural Tube

The secretion of Sonic hedgehog (Shh) from the notochord and floor plate appears to generate a ventral-to-dorsal gradient of Shh activity that directs progenitor cell identity and neuronal fate in the ventral neural tube. In principle, the establishment of this Shh activity gradient could be achieved through the graded distribution of the Shh protein itself, or could depend on additional cell surface or secreted proteins that modify the response of neural cells to Shh. Cells of the neural plate differentiate from a region of the ectoderm that has recently expressed high levels of BMPs, raising the possibility that prospective ventral neural cells are exposed to residual levels of BMP activity. We have examined whether modulation of the level of BMP signaling regulates neural cell responses to Shh, and thus might contribute to the patterning of cell types in the ventral neural tube. Using an in vitro assay of neural cell differentiation we show that BMP signaling markedly alters neural cell responses to Shh signals, eliciting a ventral-to-dorsal switch in progenitor cell identity and neuronal fate. BMP signaling is regulated by secreted inhibitory factors, including noggin and follistatin, both of which are expressed in or adjacent to the neural plate. Conversely, follistatin but not noggin produces a dorsal-to-ventral switch in progenitor cell identity and neuronal fate in response to Shh both in vitro and in vivo. These results suggest that the specification of ventral neural cell types depends on the integration of Shh and BMP signaling activities. The net level of BMP signaling within neural tissue may be regulated by follistatin and perhaps other BMP inhibitors secreted by mesodermal cell types that flank the ventral neural tube.

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.

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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