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.

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.

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.

A Xenopus homebox gene defines dorsal-ventral domains in the developing brain

Development ◽  
1993 ◽  
Vol 118 (1) ◽  
pp. 193-202 ◽  
Author(s):  
M.S. Saha ◽  
R.B. Michel ◽  
K.M. Gulding ◽  
R.M. Grainger
Keyword(s):  
Initial Step ◽  
Neural Plate ◽  
Developing Brain ◽  
Vertebrate Development ◽  
Tissue Interactions ◽  
Temporal Localization ◽  
Distinguishing Features ◽  
The Brain ◽  
Anterior Neural Plate ◽  
Anterior Posterior

One of the distinguishing features of vertebrate development is the elaboration of the anterior neural plate into forebrain and midbrain, yet little is known about the early tissue interactions that regulate pattern formation in this region or the genes that mediate these interactions. As an initial step toward analyzing the process of regionalization in the anterior-most region of the brain, we have screened an anterior neural cDNA library for homeobox clones and have identified one which we have called XeNK-2 (Xenopus NK-2) because of its homology to the NK-2 family of homeobox genes. From neurula stages, when XeNK-2 is first detectable, through hatching stages, XeNK-2 mRNA is expressed primarily in the anterior region of the brain. By swimming tadpole stages, XeNK-2 expression resolves into a set of bands positioned at the forebrain-midbrain and the midbrain-hindbrain boundaries, after which XeNK-2 transcripts are no longer detectable. In addition to localized expression along the anterior-posterior axis, XeNK-2 may also play a role in the process of regionalization along the dorsal-ventral axis of the developing brain. At all stages examined, XeNK-2 mRNA is restricted to a pair of stripes that are bilaterally symmetrical in the ventral-lateral region of the brain. To begin to identify the tissue interactions that are required for the proper spatial and temporal localization of XeNK-2, we have performed a series of explant experiments. Consistent with earlier work showing that the A/P axis is not fixed at mid-gastrula stages, we show that XeNK-2 expression is activated when assayed in gastrula stage explants taken from any region along the entire A/P axis and that the tissue interactions necessary to localize XeNK-2 along the A/P axis are not completed until later neurula stages.

Anterior mesendoderm induces mouse Engrailed genes in explant cultures

Development ◽  
1993 ◽  
Vol 118 (1) ◽  
pp. 139-149 ◽  
Author(s):  
S.L. Ang ◽  
J. Rossant
Keyword(s):  
Direct Evidence ◽  
Neural Tissue ◽  
Explant Culture ◽  
Neural Plate ◽  
Explant Cultures ◽  
Neural Marker ◽  
Engrailed Genes ◽  
Anterior Posterior

We have developed germ layer explant culture assays to study the role of mesoderm in anterior-posterior (A-P) patterning of the mouse neural plate. Using isolated explants of ectodermal tissue alone, we have demonstrated that the expression of Engrailed-1 (En-1) and En-2 genes in ectoderm is independent of mesoderm by the mid- to late streak stage, at least 12 hours before their onset of expression in the neural tube in vivo at the early somite stage. In recombination explants, anterior mesendoderm from headfold stage embryos induces the expression of En-1 and En-2 in pre- to early streak ectoderm and in posterior ectoderm from headfold stage embryos. In contrast, posterior mesendoderm from embryos of the same stage does not induce En genes in pre- to early streak ectoderm but is able to induce expression of a general neural marker, neurofilament 160 × 10(3) M(r). These results provide the first direct evidence for a role of mesendoderm in induction and regionalization of neural tissue in mouse.

Limb deformity proteins: role in mesodermal induction of the apical ectodermal ridge

Development ◽  
1997 ◽  
Vol 124 (1) ◽  
pp. 133-139 ◽  
Author(s):  
J. Kuhlman ◽  
L. Niswander
Keyword(s):  
Sonic Hedgehog ◽  
Limb Development ◽  
Apical Ectodermal Ridge ◽  
Primary Defect ◽  
Limb Deformity ◽  
Normal Morphology ◽  
Fibroblast Growth Factor 8 ◽  
Skeletal Pattern ◽  
Two Phases ◽  
And Function

During early limb development, distal tip ectoderm is induced by the underlying mesenchyme to form the apical ectodermal ridge. Subsequent limb growth and patterning depend on reciprocal signaling between the mesenchyme and ridge. Mice that are homozygous for mutations at the limb deformity (ld) locus do not form a proper ridge and the anteroposterior axis of the limb is shortened. Skeletal analyses reveal shortened limbs that involve loss and fusion of distal bones and digits, defects in both anteroposterior and proximodistal patterning. Using molecular markers and mouse-chick chimeras we examined the ridge-mesenchymal interactions to determine the origin of the ld patterning defects. In the ld ridge, fibroblast growth factor 8 (Fgf8) RNA is decreased and Fgf4 RNA is not detected. In the ld mesenchyme, Sonic hedgehog (Shh), Evx1 and Wnt5a expression is decreased. In chimeras between ld ectoderm and wild-type mesenchyme, a ridge of normal morphology and function is restored, Fgf8 and Shh are expressed normally, Fgf4 is induced and a normal skeletal pattern arises. These results suggest that the ld mesenchyme is unable to induce the formation of a completely functional ridge. This primary defect causes a disruption of ridge function and subsequently leads to the patterning defects observed in ld limbs. We propose a model in which ridge induction requires at least two phases: an early competence phase, which includes induction of Fgf8 expression, and a later differentiation phase in which Fgf4 is induced and a morphological ridge is formed. Ld proteins appear to act during the differentiation phase.

Inductive patterning of the embryonic brain in Drosophila

Development ◽  
2002 ◽  
Vol 129 (9) ◽  
pp. 2121-2128
Author(s):  
Damon T. Page
Keyword(s):  
Brain Development ◽  
Common Ancestor ◽  
Last Common Ancestor ◽  
Embryonic Brain ◽  
Germ Layers ◽  
Brain Anomaly ◽  
Prechordal Plate ◽  
Foregut Endoderm ◽  
The Brain ◽  
Brain Patterning

In vertebrates (deuterostomes), brain patterning depends on signals from adjacent tissues. For example, holoprosencephaly, the most common brain anomaly in humans, results from defects in signaling between the embryonic prechordal plate (consisting of the dorsal foregut endoderm and mesoderm) and the brain. I have examined whether a similar mechanism of brain development occurs in the protostome Drosophila, and find that the foregut and mesoderm act to pattern the fly embryonic brain. When the foregut and mesoderm of Drosophila are ablated, brain patterning is disrupted. The loss of Hedgehog expressed in the foregut appears to mediate this effect, as it does in vertebrates. One mechanism whereby these defects occur is a disruption of normal apoptosis in the brain. These data argue that the last common ancestor of protostomes and deuterostomes had a prototype of the brains present in modern animals, and also suggest that the foregut and mesoderm contributed to the patterning of this ‘proto-brain’. They also argue that the foreguts of protostomes and deuterostomes, which have traditionally been assigned to different germ layers, are actually homologous.

A study of the properties, morphogenetic potencies and prospective fate of outer and inner layers of ectodermal and chordamesodermal regions during gastrulation, in various Anuran amphibians

Development ◽  
1983 ◽  
Vol 75 (1) ◽  
pp. 67-86
Author(s):  
T. A. Dettlaff
Keyword(s):  
Outer Layer ◽  
Normal Development ◽  
Neural Plate ◽  
Ependymal Cells ◽  
Epithelial Layer ◽  
Bombina Bombina ◽  
Cell Layers ◽  
The Brain ◽  
Early Gastrula

In both the ectodermal and the chordamesodermal regions of Anuran embryos, the outer layer of cells possesses epithelial properties and has the same restricted morphogenetic potencies. It is thus interchangeable between the regions, capable of epiboly and, when underlain by notochord material, of the formation of bottle-shaped cells as at the blastoporal groove, and invagination. When taken from the chordamesoderm region, this outer layer has no inducing effect on the ectoderm of the early gastrula. In normal development the outer layer of the neural plate takes an active part in forming the neural tube cavity. It gives rise to the neuroepithelial roof of the diencephalon and medulla oblongata and, when underlain by neuroblasts that develop from the inner cell layers, to ependymal cells of the brain wall. The outer layer of the notochord material is included in the epithelial layer underlying the roof of the gastrocoel - the hypochordal plate. The inner layers of these regions consist of loosely arranged cells and normally have no epithelial properties although, when taken from the ectoderm region, they may acquire such properties upon long-term contact with the environment. However they have wide morphogenetic potencies; the differences in these potencies between cells taken from the various presumptive regions being less than the differences between outer and inner cell layers in each region. Maps are provided which show the arrangement of presumptive rudiments in the ectoderm and chordamesoderm on sagittal sections through Bombina bombina embryos in early and late gastrulation.

Sonic Hedgehog Regulation of the Neural Precursor Cell Fate During Chicken Optic Tectum Development

2017 ◽  
Vol 64 (2) ◽  
pp. 287-299 ◽  
Author(s):  
Ciqing Yang ◽  
Xiaoying Li ◽  
Qiuling Li ◽  
Han Li ◽  
Liang Qiao ◽  
...  
Keyword(s):  
Cell Fate ◽  
Sonic Hedgehog ◽  
Optic Tectum ◽  
Precursor Cell ◽  
Neural Precursor ◽  
Neural Precursor Cell

Will brain tissue grafts become an important therapy to restore visual function in cerebrally blind patients?

1995 ◽  
Vol 18 (1) ◽  
pp. 74-74
Author(s):  
Reinhard Werth
Keyword(s):  
Visual Field ◽  
Brain Tissue ◽  
Visual Function ◽  
Visual Field Loss ◽  
Embryonic Brain ◽  
Cerebral Lesions ◽  
Tissue Grafts ◽  
The Brain ◽  
Neuropsychological Methods ◽  
Blind Patients

AbstractGrafting embryonic brain tissue into the brain of patients with visual field loss due to cerebral lesions may become a method to restore visual function. This method is not without risk, however, and will only be considered in cases of complete blindness after bilateral occipital lesions, when other, risk-free neuropsychological methods fail.

Specification of the anterior hindbrain and establishment of a normal mid/hindbrain organizer is dependent on Gbx2 gene function

Development ◽  
1997 ◽  
Vol 124 (15) ◽  
pp. 2923-2934 ◽  
Author(s):  
K.M. Wassarman ◽  
M. Lewandoski ◽  
K. Campbell ◽  
A.L. Joyner ◽  
J.L. Rubenstein ◽  
...  
Keyword(s):  
Normal Development ◽  
Motor Nerve ◽  
Homeobox Gene ◽  
Neural Plate ◽  
Mouse Embryos ◽  
Loss Of Function ◽  
Isthmic Nuclei ◽  
Signaling Center ◽  
Derivatives Of ◽  
Anterior Posterior

Analysis of mouse embryos homozygous for a loss-of-function allele of Gbx2 demonstrates that this homeobox gene is required for normal development of the mid/hindbrain region. Gbx2 function appears to be necessary at the neural plate stage for the correct specification and normal proliferation or survival of anterior hindbrain precursors. It is also required to maintain normal patterns of expression at the mid/hindbrain boundary of Fgf8 and Wnt1, genes that encode signaling molecules thought to be key components of the mid/hindbrain (isthmic) organizer. In the absence of Gbx2 function, isthmic nuclei, the cerebellum, motor nerve V, and other derivatives of rhombomeres 1–3 fail to form. Additionally, the posterior midbrain in the mutant embryos appears to be extended caudally and displays abnormalities in anterior/posterior patterning. The failure of anterior hindbrain development is presumably due to the loss of Gbx2 function in the precursors of the anterior hindbrain. However, since Gbx2 expression is not detected in the midbrain it seems likely that the defects in midbrain anterior/posterior patterning result from an abnormal isthmic signaling center. These data provide genetic evidence for a link between patterning of the anterior hindbrain and the establishment of the mid/hindbrain organizer, and identify Gbx2 as a gene required for these processes to occur normally.

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