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.

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.

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.

Sonic hedgehog signaling at gastrula stages specifies ventral telencephalic cells in the chick embryo

Development ◽  
2000 ◽  
Vol 127 (15) ◽  
pp. 3283-3293 ◽  
Author(s):  
L. Gunhaga ◽  
T.M. Jessell ◽  
T. Edlund
Keyword(s):  
Sonic Hedgehog ◽  
Neural Tube ◽  
Hedgehog Signaling ◽  
Early Stage ◽  
Primitive Streak ◽  
Cell Types ◽  
Neural Cells ◽  
Sonic Hedgehog Signaling ◽  
Ventral Telencephalon ◽  
Prechordal Mesoderm

A secreted signaling factor, Sonic hedgehog (Shh), has a crucial role in the generation of ventral cell types along the entire rostrocaudal axis of the neural tube. At caudal levels of the neuraxis, Shh is secreted by the notochord and floor plate during the period that ventral cell fates are specified. At anterior prosencephalic levels that give rise to the telencephalon, however, neither the prechordal mesoderm nor the ventral neural tube expresses Shh at the time that the overt ventral character of the telencephalon becomes evident. Thus, the precise role and timing of Shh signaling relevant to the specification of ventral telencephalic identity remains unclear. By analysing neural cell differentiation in chick neural plate explants we provide evidence that neural cells acquire molecular properties characteristic of the ventral telencephalon in response to Shh signals derived from the anterior primitive streak/Hensen's node region at gastrula stages. Exposure of prospective anterior prosencephalic cells to Shh at this early stage is sufficient to initiate a temporal program of differentiation that parallels that of neurons generated normally in the medial ganglionic eminence subdivision of the ventral telencephalon.

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.

Sequence and developmental expression of AmphiDll, an amphioxus Distal-less gene transcribed in the ectoderm, epidermis and nervous system: insights into evolution of craniate forebrain and neural crest

Development ◽  
1996 ◽  
Vol 122 (9) ◽  
pp. 2911-2920 ◽  
Author(s):  
N.D. Holland ◽  
G. Panganiban ◽  
E.L. Henyey ◽  
L.Z. Holland
Keyword(s):  
Neural Crest ◽  
Neural Tube ◽  
Expression Patterns ◽  
Neural Plate ◽  
Epidermal Cells ◽  
Developmental Expression ◽  
Neural Cells ◽  
Dorsoventral Axis ◽  
Dynamic Expression ◽  
Cerebral Vesicle

The dynamic expression patterns of the single amphioxus Distal-less homolog (AmphiDll) during development are consistent with successive roles of this gene in global regionalization of the ectoderm, establishment of the dorsoventral axis, specification of migratory epidermal cells early in neurulation and the specification of forebrain. Such a multiplicity of Distal-less functions probably represents an ancestral chordate condition and, during craniate evolution, when this gene diversified into a family of six or so members, the original functions evidently tended to be parcelled out among the descendant genes. In the amphioxus gastrula, AmphiDll is expressed throughout the animal hemisphere (presumptive ectoderm), but is soon downregulated dorsally (in the presumptive neural plate). During early neurulation, AmphiDll-expressing epidermal cells flanking the neural plate extend lamellipodia, appear to migrate over it and meet mid-dorsally. Midway in neurulation, cells near the anterior end of the neural plate begin expressing AmphiDll and, as neurulation terminates, these cells are incorporated into the dorsal part of the neural tube, which forms by a curling of the neural plate. This group of AmphiDll-expressing neural cells and a second group expressing the gene a little later and even more anteriorly in the neural tube demarcate a region that comprises the anterior three/fourths of the cerebral vesicle; this region of the amphioxus neural tube, as judged by neural expression domains of craniate Distal-less-related genes, is evidently homologous to the craniate forebrain. Our results suggest that craniates evolved from an amphioxus-like creature that had the beginnings of a forebrain and possibly a precursor of neural crest - namely, the cell population leading the epidermal overgrowth of the neural plate during early neurulation.

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.

Calcium and neurulation in mammalian embryos

Development ◽  
1985 ◽  
Vol 89 (1) ◽  
pp. 1-14
Author(s):  
Martin J. Smedley ◽  
Martin Stanisstreet
Keyword(s):  
Neural Tube ◽  
Divalent Cations ◽  
Neural Cells ◽  
Cellular Mechanisms ◽  
Rat Embryos ◽  
Transmission Electron ◽  
Mammalian Embryos ◽  
Neural Ectoderm ◽  
Calcium And Magnesium

The role of calcium in neurulation in rat embryos has been studied. Rat embryos at 10·4 days of gestation, when the cephalic neural folds have elevated but not fused, have been cultured in various media, and the effects of these media on the morphology of the cephalic neural folds have been observed by scanning and transmission electron microscopy. Embryos cultured in serum containing EDTA or EGTA, or in saline without divalent cations exhibit opening, then folding back (‘collapse’) of the cephalic neural folds. The neural cells lose their elongated shape and become rounded. Older embryos in which the cephalic neural folds have already fused do not show collapse of the neural tube. Culture of 10·4-day rat embryos with elevated but unfused cephalic neural folds in calcium- and magnesium-free saline to which either calcium or magnesium has been restored shows that calcium is the divalent cation which is essential for the maintenance of the elevated neural folds. In the presence of calcium, lanthanum, which competes for calcium sites, causes opening but not collapse of the elevated cephalic neural folds. Embryos treated with trypsin show dissociation of the lateral (non-neural) ectoderm but the neural folds remain elevated. If embryos in which the cephalic neural folds have been caused to collapse are further cultured in serum the folds re-elevate, although normal neural tube morphology is not completely regained. The possible implications of these observations to the understanding of the cellular mechanisms of normal neurulation, and of neural tube malformations are discussed.

Neural tube closure in Xenopus laevis involves medial migration, directed protrusive activity, cell intercalation and convergent extension

Development ◽  
1999 ◽  
Vol 126 (20) ◽  
pp. 4547-4556 ◽  
Author(s):  
L.A. Davidson ◽  
R.E. Keller
Keyword(s):  
Confocal Microscopy ◽  
Xenopus Laevis ◽  
Neural Crest ◽  
Neural Tube ◽  
Neural Plate ◽  
Neural Cells ◽  
Dorsal Midline ◽  
Cell Movements ◽  
Dorsal Neural Tube

We have characterized the cell movements and prospective cell identities as neural folds fuse during neural tube formation in Xenopus laevis. A newly developed whole-mount, two-color fluorescent RNA in situ hybridization method, visualized with confocal microscopy, shows that the dorsal neural tube gene xpax3 and the neural-crest-specific gene xslug are expressed far lateral to the medial site of neural fold fusion and that expression moves medially after fusion. To determine whether cell movements or dynamic changes in gene expression are responsible, we used low-light videomicroscopy followed by fluorescent in situ and confocal microscopy. These methods revealed that populations of prospective neural crest and dorsal neural tube cells near the lateral margin of the neural plate at the start of neurulation move to the dorsal midline using distinctive forms of motility. Before fold fusion, superficial neural cells apically contract, roll the neural plate into a trough and appear to pull the superficial epidermal cell sheet medially. After neural fold fusion, lateral deep neural cells move medially by radially intercalating between other neural cells using two types of motility. The neural crest cells migrate as individual cells toward the dorsal midline using medially directed monopolar protrusions. These movements combine the two lateral populations of neural crest into a single medial population that form the roof of the neural tube. The remaining cells of the dorsal neural tube extend protrusions both medially and laterally bringing about radial intercalation of deep and superficial cells to form a single-cell-layered, pseudostratified neural tube. While ours is the first description of medially directed cell migration during neural fold fusion and re-establishment of the neural tube, these complex cell behaviors may be involved during cavitation of the zebrafish neural keel and secondary neurulation in the posterior axis of chicken and mouse.

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.

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.

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