scholarly journals XASH genes promote neurogenesis in Xenopus embryos

Development ◽  
1994 ◽  
Vol 120 (12) ◽  
pp. 3649-3655 ◽  
Author(s):  
B. Ferreiro ◽  
C. Kintner ◽  
K. Zimmerman ◽  
D. Anderson ◽  
W.A. Harris
Keyword(s):  
Neural Development ◽  
Neural Induction ◽  
Neural Tissue ◽  
Neural Plate ◽  
Binding Partner ◽  
Helix Loop Helix ◽  
Neural Genes ◽  
Dorsal Ectoderm ◽  
Bhlh Transcription Factors ◽  
Beta Tubulin Gene

Neural development in Drosophila is promoted by a family of basic helix-loop-helix (bHLH) transcription factors encoded within the Achaete Scute-Complex (AS-C). XASH-3, a Xenopus homolog of the Drosophila AS-C genes, is expressed during neural induction within a portion of the dorsal ectoderm that gives rise to the neural plate and tube. Here, we show that XASH-3, when expressed with the promiscuous binding partner XE12, specifically activates the expression of neural genes in naive ectoderm, suggesting that XASH-3 promotes neural development. Moreover, XASH-3/XE12 RNA injections into embryos lead to hypertrophy of the neural tube. Interestingly, XASH-3 misexpression does not lead to the formation of ectopic neural tissue in ventral regions, suggesting that the domain of XASH proneural function is restricted in the embryo. In contrast to the neural inducer noggin, which permanently activates the NCAM gene, the activation of neural genes by XASH-3/XE12 is not stable in naive ectoderm, yet XASH-3/XE12 powerfully and stably activates NCAM, Neurofilament and type III beta-tubulin gene expression in noggin-treated ectoderm. These results show that the XASH-3 promotes neural development, and suggest that its activity depends on additional factors which are induced in ectoderm by factors such as noggin.

Patterning of the neural ectoderm of Xenopus laevis by the amino-terminal product of hedgehog autoproteolytic cleavage

Development ◽  
1995 ◽  
Vol 121 (8) ◽  
pp. 2349-2360 ◽  
Author(s):  
C.J. Lai ◽  
S.C. Ekker ◽  
P.A. Beachy ◽  
R.T. Moon
Keyword(s):  
Gene Family ◽  
Neural Induction ◽  
Neural Tissue ◽  
Internal Deletion ◽  
Anteroposterior Patterning ◽  
Amino Terminal ◽  
Neural Genes ◽  
Neural Ectoderm ◽  
Amino Terminal Domain ◽  
Autoproteolytic Cleavage

The patterns of embryonic expression and the activities of Xenopus members of the hedgehog gene family are suggestive of role in neural induction and patterning. We report that these hedgehog polypeptides undergo autoproteolytic cleavage. Injection into embryos of mRNAs encoding Xenopus banded-hedgehog (X-bhh) or the amino-terminal domain (N) demonstrates that the direct inductive activities of X-bhh are encoded by N. In addition, both N and X-bhh pattern neural tissue by elevating expression of anterior neural genes. Unexpectedly, an internal deletion of X-bhh (delta N-C) was found to block the activity of X-bhh and N in explants and to reduce dorsoanterior structures in embryos. As elevated hedgehog activity increases the expression of anterior neural genes, and as delta N-C reduces dorsoanterior structures, these complementary data support a role for hedgehog in neural induction and anteroposterior patterning.

scholarly journals Neural Induction, Neural Fate Stabilization, and Neural Stem Cells

2002 ◽  
Vol 2 ◽  
pp. 1147-1166 ◽  
Author(s):  
Sally A. Moody ◽  
Hyun-Soo Je
Keyword(s):  
Stem Cells ◽  
Embryonic Stem Cells ◽  
Neural Stem Cells ◽  
Neural Development ◽  
Current Knowledge ◽  
Embryonic Stem ◽  
Neural Induction ◽  
Neural Plate ◽  
Natural Rate ◽  
Neural Fate

The promise of stem cell therapy is expected to greatly benefit the treatment of neurodegenerative diseases. An underlying biological reason for the progressive functional losses associated with these diseases is the extremely low natural rate of self-repair in the nervous system. Although the mature CNS harbors a limited number of self-renewing stem cells, these make a significant contribution to only a few areas of brain. Therefore, it is particularly important to understand how to manipulate embryonic stem cells and adult neural stem cells so their descendants can repopulate and functionally repair damaged brain regions. A large knowledge base has been gathered about the normal processes of neural development. The time has come for this information to be applied to the problems of obtaining sufficient, neurally committed stem cells for clinical use. In this article we review the process of neural induction, by which the embryonic ectodermal cells are directed to form the neural plate, and the process of neural�fate stabilization, by which neural plate cells expand in number and consolidate their neural fate. We will present the current knowledge of the transcription factors and signaling molecules that are known to be involved in these processes. We will discuss how these factors may be relevant to manipulating embryonic stem cells to express a neural fate and to produce large numbers of neurally committed, yet undifferentiated, stem cells for transplantation therapies.

Chordin regulates primitive streak development and the stability of induced neural cells, but is not sufficient for neural induction in the chick embryo

Development ◽  
1998 ◽  
Vol 125 (3) ◽  
pp. 507-519 ◽  
Author(s):  
A. Streit ◽  
K.J. Lee ◽  
I. Woo ◽  
C. Roberts ◽  
T.M. Jessell ◽  
...  
Keyword(s):  
Neural Induction ◽  
Neural Tissue ◽  
Primitive Streak ◽  
Neural Plate ◽  
Neural Cells ◽  
Morphogenetic Protein ◽  
Neural Markers ◽  
Bmp Signalling ◽  
The Stability ◽  
Area Pellucida

We have investigated the role of Bone Morphogenetic Protein 4 (BMP-4) and a BMP antagonist, chordin, in primitive streak formation and neural induction in amniote embryos. We show that both BMP-4 and chordin are expressed before primitive streak formation, and that BMP-4 expression is downregulated as the streak starts to form. When BMP-4 is misexpressed in the posterior area pellucida, primitive streak formation is inhibited. Misexpression of BMP-4 also arrests further development of Hensen's node and axial structures. In contrast, misexpression of chordin in the anterior area pellucida generates an ectopic primitive streak that expresses mesoderm and organizer markers. We also provide evidence that chordin is not sufficient to induce neural tissue in the chick. Misexpression of chordin in regions outside the future neural plate does not induce the early neural markers L5, Sox-3 or Sox-2. Furthermore, neither BMP-4 nor BMP-7 interfere with neural induction when misexpressed in the presumptive neural plate before or after primitive streak formation. However, chordin can stabilise the expression of early neural markers in cells that have already received neural inducing signals. These results suggest that the regulation of BMP signalling by chordin plays a role in primitive streak formation and that chordin is not sufficient to induce neural tissue.

Expression of Xenopus N-CAM RNA in ectoderm is an early response to neural induction

Development ◽  
1987 ◽  
Vol 99 (3) ◽  
pp. 311-325 ◽  
Author(s):  
C.R. Kintner ◽  
D.A. Melton
Keyword(s):  
Neural Development ◽  
Transcriptional Activation ◽  
Neural Induction ◽  
Early Response ◽  
Neural Plate ◽  
Cdna Clones ◽  
Epidermal Tissue ◽  
Early Expression ◽  
Neural Ectoderm

We have isolated Xenopus laevis N-CAM cDNA clones and used these to study the expression of N-CAM RNA during neural induction. The results show that the first marked increase in N-CAM RNA levels occurs during gastrulation when mesoderm comes in contact with ectoderm and induces neural development. In situ hybridization results show that the early expression of N-CAM RNA is localized to the neural plate and its later expression is confined to the neural tube. Induction experiments with explanted germ layers show that N-CAM RNA is not expressed in ectoderm unless there is contact with inducing tissue. Together these results suggest an approach to studying how ectoderm is committed to form neural rather than epidermal tissue. Specifically, the data suggest that neural commitment is marked and perhaps mediated by the transcriptional activation of genes, like N-CAM, in the neural ectoderm.

A posteriorising factor, retinoic acid, reveals that anteroposterior patterning controls the timing of neuronal differentiation in Xenopus neuroectoderm

Development ◽  
1996 ◽  
Vol 122 (11) ◽  
pp. 3409-3418 ◽  
Author(s):  
N. Papalopulu ◽  
C. Kintner
Keyword(s):  
Retinoic Acid ◽  
Neuronal Differentiation ◽  
Neural Tissue ◽  
Neural Plate ◽  
Neural Tube Closure ◽  
Proneural Gene ◽  
Anteroposterior Patterning ◽  
Neural Genes ◽  
Tube Closure

During early development of the Xenopus central nervous system (CNS), neuronal differentiation can be detected posteriorly at neural plate stages but is delayed anteriorly until after neural tube closure. A similar delay in neuronal differentiation also occurs in the anterior neural tissue that forms in vitro when isolated ectoderm is treated with the neural inducer noggin. Here we examine the factors that control the timing of neuronal differentiation both in embryos and in neural tissue induced by noggin (noggin caps). We show that the delay in neuronal differentiation that occurs in noggin caps cannot be overcome by inhibiting the activity of the neurogenic gene, X-Delta-1, which normally inhibits neuronal differentiation, suggesting that it represents a novel level of regulation. Conversely, we show that the timing of neuronal differentiation can be changed from late to early after treating noggin caps or embryos with retinoic acid (RA), a putative posteriorising agent. Concommittal with changes in the timing of neuronal differentiation, RA suppresses the expression of anterior neural genes and promotes the expression of posterior neural genes. The level of early neuronal differentiation induced by RA alone is greatly increased by the additional expression of the proneural gene, XASH3. These results indicate that early neuronal differentiation in neuralised ectoderm requires posteriorising signals, as well as signals that promote the activity of proneural genes such as XASH3. In addition, these result suggest that neuronal differentiation is controlled by anteroposterior (A-P) patterning, which exerts a temporal control on the onset of neuronal differentiation.

Histological features of neural induction in Xenopus laevis

Development ◽  
1971 ◽  
Vol 26 (3) ◽  
pp. 543-570
Author(s):  
D. Tarin
Keyword(s):  
Xenopus Laevis ◽  
Neural Induction ◽  
Neural Plate ◽  
Paraxial Mesoderm ◽  
Intestinal Tube ◽  
Spinal Cord Regions ◽  
The Central Nervous System ◽  
Dorsal Ectoderm ◽  
Two Stages ◽  
The Brain

It was first established by grafting experiments that neural induction occurs in Xenopus laevis and that it is the mesoderm in the dorsal lip of the blastopore which normally exercises this function. The subsequent histological work provided the following information: At stage 10½ mesodermal invagination was already well under way, in advance of the formation of the archenteric cavity. This confirms the earlier observations of Nieuwkoop & Florschutz(1950). The first evidence of neural induction, thickening of the mid-dorsal ectoderm combined with the development of an inner tier of columnar cells, occurred at stage 11½. By stage 12 there was generalized thickening of the dorsal ectoderm and between stage 12½ and 13 the brain and spinal cord regions of the neural plate became distinguishable. The dorsal mesoderm segregated into notochord rudiment and two lateral masses at stage 13 and the latter further subdivided into paraxial mesoderm and lateral plates by stage 14. The margins of the neural plate were clearly distinguished from presumptive epidermis by stage 15 and the median neural groove was also well marked. In the next two stages the folding of the neural plate in the line of this groove proceeded rapidly. The dorsoventral enlargement of the somites and the relative shrinkage of the notochord were considered to contribute to the mechanism of neurulation. Regionalization of the brain into prosencephalon, mesencephalon and rhombencephalon was in progress at stages 18 and 19. These results indicate that induction consists of an initial activation of dorsal ectoderm (generalized thickening) followed by gradual transformation of the neural plate to form the different parts of the central nervous system (regionalization). Intercellular metachromatic material was noted in various parts of the embryo. This was most plentiful between stage 10½ and stage 13 and thereafter gradually decreased. It was the only feature which persisted long enough to represent a possible inductive agent. At all stages the archenteron was lined with a continuous layer of endoderm. This indicates that the mode of formation of the gastro-intestinal tube in Xenopus is different to that in urodeles. It further implies that the mesoderm is not present on the blastular surface prior to gastrulation but lies in deeper layers.

scholarly journals Fgf/Ets signalling in Xenopus ectoderm initiates neural induction and patterning in an autonomous and paracrine manners

2020 ◽  
Author(s):  
Ikuko Hongo ◽  
Harumasa Okamoto
Keyword(s):  
Neural Development ◽  
Neural Induction ◽  
Dominant Negative ◽  
Neural Patterning ◽  
Paracrine Signalling ◽  
Neural Genes ◽  
Morphogenetic Protein ◽  
Bmp Signalling

ABSTRACTFibroblast growth factor (Fgf) and anti-bone morphogenetic protein (Bmp) signals are derived from the organiser of mesoderm origin and cooperate to promote Xenopus neural development from the gastrula ectoderm. Using antisense oligos to Fgf2 and Fgf8 and dominant-negative Ets transcription factors, we showed that the expression of Fgf2, Fgf8, and Ets in ectoderm cells is essential to initiate neural induction both in vivo and in vitro. Our findings show that neural induction is initiated primarily by autonomous signalling in ectoderm cells, rather than by paracrine signalling from organiser cells. The signalling in ectoderm cells is transduced via the Fgf/Ras/Mapk/Ets pathway, independent of Bmp signal inhibition via the Fgf/Ras/Mapk/Smad1 route, as indicated by earlier studies. Through the same pathway, Fgfs activated position-specific neural genes dose-dependently along the anteroposterior axis in cultured ectoderm cells. The expression of these genes coincides with the establishment of the activated Ets gradient within the gastrula ectoderm. Organiser cells, being located posteriorly to the ectoderm, secrete Fgfs as gastrulation proceeds, which among several candidate molecules initially promote neural patterning of the induced neuroectoderm as morphogens.Summary statementFgf/Ets signalling in ectodermal cells is required to initiate the expression of both anterior and posterior neural genes from the late blastula to gastrula stages, independent of anti-Bmp signalling.

TheDrosophila daughterlessgene autoregulates and is controlled by both positive and negativecisregulation

Development ◽  
2001 ◽  
Vol 128 (23) ◽  
pp. 4705-4714 ◽  
Author(s):  
John E. Smith ◽  
Claire Cronmiller
Keyword(s):  
Negative Regulation ◽  
Fourth Chromosome ◽  
Developmentally Regulated ◽  
Tissue Specific ◽  
Binding Partner ◽  
Helix Loop Helix ◽  
Specific Manner ◽  
Specific Allele ◽  
A Cell ◽  
Bhlh Transcription Factors

As the only class I helix-loop-helix transcription factor in Drosophila, Daughterless (Da) has generally been regarded as a ubiquitously expressed binding partner for other developmentally regulated bHLH transcription factors. From analysis of a novel tissue-specific allele, dalyh, we show that da expression is not constitutive, but is dynamically regulated. This transcriptional regulation includes somatic ovary-specific activation, autoregulation and negative regulation. Unexpectedly, the diverse functions of da may require that expression levels be tightly controlled in a cell and/or tissue-specific manner. Our analysis of dalyh identifies it as the first springer insertion that functions as an insulating element, with its disruptive activity mediated by the product of a fourth chromosome gene, Suppressor of lyh [Su(lyh)].

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.

Mechanism of anteroposterior axis specification in vertebrates. Lessons from the amphibians

Development ◽  
1992 ◽  
Vol 114 (2) ◽  
pp. 285-302 ◽  
Author(s):  
J.M. Slack ◽  
D. Tannahill
Keyword(s):  
Molecular Markers ◽  
Expression Patterns ◽  
Signal Transduction Pathway ◽  
Homeobox Gene ◽  
Neural Induction ◽  
High Sensitivity ◽  
Neural Plate ◽  
Mesoderm Induction ◽  
Inducing Factors ◽  
Almost All

Interest in the problem of anteroposterior specification has quickened because of our near understanding of the mechanism in Drosophila and because of the homology of Antennapedia-like homeobox gene expression patterns in Drosophila and vertebrates. But vertebrates differ from Drosophila because of morphogenetic movements and interactions between tissue layers, both intimately associated with anteroposterior specification. The purpose of this article is to review classical findings and to enquire how far these have been confirmed, refuted or extended by modern work. The “pre-molecular” work suggests that there are several steps to the process: (i) Formation of anteroposterior pattern in mesoderm during gastrulation with posterior dominance. (ii) Regional specific induction of ectoderm to form neural plate. (iii) Reciprocal interactions from neural plate to mesoderm. (iv) Interactions within neural plate with posterior dominance. Unfortunately, almost all the observable markers are in the CNS rather than in the mesoderm where the initial specification is thought to occur. This has meant that the specification of the mesoderm has been assayed indirectly by transplantation methods such as the Einsteckung. New molecular markers now supplement morphological ones but they are still mainly in the CNS and not the mesoderm. A particular interest attaches to the genes of the Antp-like HOX clusters since these may not only be markers but actual coding factors for anteroposterior levels. We have a new understanding of mesoderm induction based on the discovery of activins and fibroblast growth factors (FGFs) as candidate inducing factors. These factors have later consequences for anteroposterior pattern with activin tending to induce anterior, and FGF posterior structures. Recent work on neural induction has implicated cAMP and protein kinase C (PKC) as elements of the signal transduction pathway and has provided new evidence for the importance of tangential neural induction. The regional specificity of neural induction has been reinvestigated using molecular markers and provides conclusions rather similar to the classical work. Defects in the axial pattern may be produced by retinoic acid but it remains unclear whether its effects are truly coordinate ones or are concentrated in certain regions of high sensitivity. In general the molecular studies have supported and reinforced the “pre-molecular ones”. Important questions still remain: (i) How much pattern is there in the mesoderm (how many states?) (ii) How is this pattern generated by the invaginating organizer? (iii) Is there one-to-one transmission of codings to the neural plate? (iv) What is the nature of the interactions within the neural plate? (v) Are the HOX cluster genes really the anteroposterior codings?

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