Caudalization by the amphibian organizer: brachyury, convergent extension and retinoic acid

Development ◽  
1994 ◽  
Vol 120 (11) ◽  
pp. 3051-3062 ◽  
Author(s):  
T. Yamada
Keyword(s):  
Cell Motility ◽  
Neural Development ◽  
Marginal Zone ◽  
Floor Plate ◽  
Convergent Extension ◽  
Neural Tissues ◽  
Dorsal Mesoderm ◽  
The One ◽  
Cell Intercalation ◽  
Morphogenetic Effects

Caudalization, which is proposed to be one of two functions of the amphibian organizer, initiates posterior pathways of neural development in the dorsalized ectoderm. In the absence of caudalization, dorsalized ectoderm only expresses the most anterior (archencephalic) differentiation. In the presence of caudalization, dorsalized ectorderm develops various levels of posterior neural tissues, depending on the extent of caudalization. A series of induction experiments have shown that caudalization is mediated by convergent extension: cell motility that is based on directed cell intercalation, and is essential for the morphogenesis of posterior axial tissues. During amphibian development, convergent extension is first expressed all-over the mesoderm and, after mesoderm involution, it becomes localized to the posterior mid-dorsal mesoderm, which produces notochord. This expression pattern of specific down regulation of convergent extension is also followed by the expression of the brachyury homolog. Furthermore, mouse brachyury has been implicated in the regulation of tissue elongation on the one hand, and in the control of posterior differentiation on the other. These observations suggest that protein encoded by the brachyury homolog controls the expression of convergent extension in the mesoderm. The idea is fully corroborated by a genetic study of mouse brachyury, which demonstrates that the gene product produces elongation of the posterior embryonic axis. However, there exists evidence for the induction of posterior dorsal mesodermal tissues, if brachyury homolog protein is expressed in the ectoderm. In both cases the brachyury homolog contributes to caudalization. A number of other genes appear to be involved in caudalization. The most important of these is pintavallis, which contains a fork-head DNA binding domain. It is first expressed in the marginal zone. After mesoderm involution, it is present not only in the presumptive notochord, but also in the floor plate. This is in contrast to the brachyury homolog, whose expression is restricted to mesoderm. The morphogenetic effects of exogenous RA on anteroposterior specification during amphibian embryogenesis are reviewed. The agent inhibits archencephalic differentiation and enhances differentiation of deuterencephalic and trunk levels. Thus the effect of exogenous RA on morphogenesis of CNS is very similar to that of caudalization, which is proposed to occur through the normal action of the organizer. According to a detailed analysis of the effect of lithium on morphogenesis induced by the Cynops organizer, lithium has a caudalizing effect closely comparable with that of RA. Furthermore, lithium induces convergent extension in the prechordal plate, which normally does not show cell motility.(ABSTRACT TRUNCATED AT 400 WORDS)

scholarly journals Mechanisms of convergence and extension by cell intercalation

2000 ◽  
Vol 355 (1399) ◽  
pp. 897-922 ◽  
Author(s):  
Ray Keller ◽  
Lance Davidson ◽  
Anna Edlund ◽  
Tamira Elul ◽  
Max Ezin ◽  
...  
Keyword(s):  
Essential Elements ◽  
Floor Plate ◽  
Cell Cortex ◽  
Convergent Extension ◽  
Mesoderm Cell ◽  
Mesodermal Cell ◽  
Cell Traction ◽  
Convergence And Extension ◽  
A Cell ◽  
Cell Intercalation

The cells of many embryonic tissues actively narrow in one dimension (convergence) and lengthen in the perpendicular dimension (extension). Convergence and extension are ubiquitous and important tissue movements in metazoan morphogenesis. In vertebrates, the dorsal axial and paraxial mesodermal tissues, the notochordal and somitic mesoderm, converge and extend. In amphibians as well as a number of other organisms where these movements appear, they occur by mediolateral cell intercalation, the rearrangement of cells along the mediolateral axis to produce an array that is narrower in this axis and longer in the anteroposterior axis. In amphibians, mesodermal cell intercalation is driven by bipolar, mediolaterally directed protrusive activity, which appears to exert traction on adjacent cells and pulls the cells between one another. In addition, the notochordal–somitic boundary functions in convergence and extension by ‘capturing’ notochordal cells as they contact the boundary, thus elongating the boundary. The prospective neural tissue also actively converges and extends parallel with the mesoderm. In contrast to the mesoderm, cell intercalation in the neural plate normally occurs by monopolar protrusive activity directed medially, towards the midline notoplate–floor–plate region. In contrast, the notoplate–floor–plate region appears to converge and extend by adhering to and being towed by or perhaps migrating on the underlying notochord. Converging and extending mesoderm stiffens by a factor of three or four and exerts up to 0.6 μN force. Therefore, active, force–producing convergent extension, the mechanism of cell intercalation, requires a mechanism to actively pull cells between one another while maintaining a tissue stiffness sufficient to push with a substantial force. Based on the evidence thus far, a cell–cell traction model of intercalation is described. The essential elements of such a morphogenic machine appear to be (i) bipolar, mediolaterally orientated or monopolar, medially directed protrusive activity; (ii) this protrusive activity results in mediolaterally orientated or medially directed traction of cells on one another; (iii) tractive protrusions are confined to the ends of the cells; (iv) a mechanically stable cell cortex over the bulk of the cell body which serves as a movable substratum for the orientated or directed cell traction. The implications of this model for cell adhesion, regulation of cell motility and cell polarity, and cell and tissue biomechanics are discussed.

Microtubule disruption reveals that Spemann's organizer is subdivided into two domains by the vegetal alignment zone

Development ◽  
1997 ◽  
Vol 124 (4) ◽  
pp. 895-906 ◽  
Author(s):  
M.C. Lane ◽  
R. Keller
Keyword(s):  
Marginal Zone ◽  
Axis Formation ◽  
Convergent Extension ◽  
Microtubule Depolymerization ◽  
Microtubule Disruption ◽  
Spemann's Organizer ◽  
And Function ◽  
Cell Intercalation ◽  
Somitic Mesoderm ◽  
Anterior Posterior

Mediolateral cell intercalation is proposed to drive morphogenesis of the primary embryonic axis in Xenopus. Mediolateral intercalation begins in a group of cells called the vegetal alignment zone, a subpopulation of cells in Spemann's organizer, and spreads through much of the marginal zone. To understand the functions of the vegetal alignment zone during gastrulation and axis formation, we have inhibited its formation by disrupting microtubules with nocodazole in early gastrula embryos. In such embryos, mediolateral intercalation, involution and convergent extension of the marginal zone do not occur. Although cell motility continues, and the anterior notochordal and somitic mesoderm differentiate in the pre-involution marginal zone, posterior notochordal and somitic mesoderm do not differentiate. In contrast, microtubule depolymerization in midgastrula embryos, after the vegetal alignment zone has formed, does not inhibit mediolateral cell intercalation, involution and convergent extension, or differentiation of posterior notochord and somites. We conclude that microtubules are required only for orienting and polarizing at stage 101/2 the first cells that undergo mediolateral intercalation and form the vegetal alignment zone, and not for subsequent morphogenesis. These results demonstrate that microtubules are required to form the vegetal alignment zone, and that both microtubules and the vegetal alignment zone play critical roles in the inductive and morphogenetic activities of Spemann's organizer. In addition, our results suggest that Spemann's organizer contains multiple organizers, which act in succession and change their location and function during gastrulation to generate the anterior/posterior axis in Xenopus.

scholarly journals Cadherins in early neural development

2021 ◽  
Author(s):  
Karolina Punovuori ◽  
Mattias Malaguti ◽  
Sally Lowell
Keyword(s):  
Adhesion Molecules ◽  
Cell Fate ◽  
Neural Development ◽  
Ex Vivo ◽  
Directed Differentiation ◽  
Culture Dish ◽  
Cell Identity ◽  
Cell Fate Decisions ◽  
Neural Tissues ◽  
And Function

AbstractDuring early neural development, changes in signalling inform the expression of transcription factors that in turn instruct changes in cell identity. At the same time, switches in adhesion molecule expression result in cellular rearrangements that define the morphology of the emerging neural tube. It is becoming increasingly clear that these two processes influence each other; adhesion molecules do not simply operate downstream of or in parallel with changes in cell identity but rather actively feed into cell fate decisions. Why are differentiation and adhesion so tightly linked? It is now over 60 years since Conrad Waddington noted the remarkable "Constancy of the Wild Type” (Waddington in Nature 183: 1654–1655, 1959) yet we still do not fully understand the mechanisms that make development so reproducible. Conversely, we do not understand why directed differentiation of cells in a dish is sometimes unpredictable and difficult to control. It has long been suggested that cells make decisions as 'local cooperatives' rather than as individuals (Gurdon in Nature 336: 772–774, 1988; Lander in Cell 144: 955–969, 2011). Given that the cadherin family of adhesion molecules can simultaneously influence morphogenesis and signalling, it is tempting to speculate that they may help coordinate cell fate decisions between neighbouring cells in the embryo to ensure fidelity of patterning, and that the uncoupling of these processes in a culture dish might underlie some of the problems with controlling cell fate decisions ex-vivo. Here we review the expression and function of cadherins during early neural development and discuss how and why they might modulate signalling and differentiation as neural tissues are formed.

XIPOU 2 is a potential regulator of Spemann's Organizer

Development ◽  
1997 ◽  
Vol 124 (6) ◽  
pp. 1179-1189 ◽  
Author(s):  
S.E. Witta ◽  
S.M. Sato
Keyword(s):  
Gene Expression ◽  
Wnt Pathway ◽  
Marginal Zone ◽  
Branchial Arch ◽  
Class Iii ◽  
Domain Family ◽  
Potent Inducer ◽  
Pou Domain ◽  
Spemann's Organizer ◽  
Dorsal Mesoderm

XIPOU 2, a member of the class III POU-domain family, is expressed initially at mid-blastula transition (MBT) and during gastrulation in the entire marginal zone mesoderm, including Spemann's Organizer (the Organizer). To identify potential targets of XIPOU 2, the interaction of XIPOU 2 with other genes co-expressed in the Organizer was examined by microinjecting XIPOU 2's mRNA into the lineage of cells that contributes to the Organizer, head mesenchyme and prechordal plate. XIPOU 2 suppresses the expression of a number of dorsal mesoderm-specific genes, including gsc, Xlim-1, Xotx2, noggin and chordin, but not Xnot. As a consequence of the suppression of dorsal mesoderm gene expression, bone morphogenetic factor-4 (Bmp-4), a potent inducer of ventral mesoderm, is activated in the Organizer. Gsc is a potential target of XIPOU 2. XIPOU 2 is capable of binding a class III POU protein binding site (CATTAAT) that is located within the gsc promoter, in the activin-inducible (distal) element. Furthermore, XIPOU 2 suppresses the activation of the gsc promoter by activin signaling. At the neurula and tailbud stages, dorsoanterior structures are affected: embryos displayed micropthalmia and the loss of the first branchial arch, as detected by the expression of pax-6, Xotx2 and en-2. By examining events downstream from the Wnt and chordin pathways, we determined that XIPOU 2, when overexpressed, acts specifically in the Organizer, downstream from GSK-3beta of the Wnt pathway and upstream from chordin. The interference in dorsalizing events caused by XIPOU 2 was rescued by chordin. Thus, in addition to its direct neuralizing ability, in a different context, XIPOU 2 has the potential to antagonize dorsalizing events in the Organizer.

bozozok and squint act in parallel to specify dorsal mesoderm and anterior neuroectoderm in zebrafish

Development ◽  
2000 ◽  
Vol 127 (12) ◽  
pp. 2583-2592 ◽  
Author(s):  
H.I. Sirotkin ◽  
S.T. Dougan ◽  
A.F. Schier ◽  
W.S. Talbot
Keyword(s):  
Neural Development ◽  
Mutational Analysis ◽  
Homeobox Gene ◽  
Beta Catenin ◽  
Neural Patterning ◽  
Blastula Stage ◽  
Mesoderm Development ◽  
Dorsal Mesoderm ◽  
Family Gene ◽  
Bmp Antagonists

In vertebrate embryos, maternal (beta)-catenin protein activates the expression of zygotic genes that establish the dorsal axial structures. Among the zygotically acting genes with key roles in the specification of dorsal axial structures are the homeobox gene bozozok (boz) and the nodal-related (TGF-(beta) family) gene squint (sqt). Both genes are expressed in the dorsal yolk syncytial layer, a source of dorsal mesoderm inducing signals, and mutational analysis has indicated that boz and sqt are required for dorsal mesoderm development. Here we examine the regulatory interactions among boz, sqt and a second nodal-related gene, cyclops (cyc). Three lines of evidence indicate that boz and sqt act in parallel to specify dorsal mesoderm and anterior neuroectoderm. First, boz requires sqt function to induce high levels of ectopic dorsal mesoderm, consistent with sqt acting either downstream or in parallel to boz. Second, sqt mRNA is expressed in blastula stage boz mutants, indicating that boz is not essential for activation of sqt transcription, and conversely, boz mRNA is expressed in blastula stage sqt mutants. Third, boz;sqt double mutants have a much more severe phenotype than boz and sqt single mutants. Double mutants consistently lack the anterior neural tube and axial mesoderm, and ventral fates are markedly expanded. Expression of chordin and noggin1 is greatly reduced in boz;sqt mutants, indicating that the boz and sqt pathways have overlapping roles in activating secreted BMP antagonists. In striking contrast to boz;sqt double mutants, anterior neural fates are specified in boz;sqt;cyc triple mutants. This indicates that cyc represses anterior neural development, and that boz and sqt counteract this repressive function. Our results support a model in which boz and sqt act in parallel to induce dorsalizing BMP-antagonists and to counteract the repressive function of cyc in neural patterning.

The origins of primitive blood in Xenopus: implications for axial patterning

Development ◽  
1999 ◽  
Vol 126 (3) ◽  
pp. 423-434 ◽  
Author(s):  
M.C. Lane ◽  
W.C. Smith
Keyword(s):  
Xenopus Laevis ◽  
Marginal Zone ◽  
Cell Stage ◽  
Axial Patterning ◽  
Xenopus Embryos ◽  
Spemann's Organizer ◽  
Dorsal Mesoderm

The marginal zone in Xenopus laevis is proposed to be patterned with dorsal mesoderm situated near the upper blastoporal lip and ventral mesoderm near the lower blastoporal lip. We determined the origins of the ventralmost mesoderm, primitive blood, and show it arises from all vegetal blastomeres at the 32-cell stage, including blastomere C1, a progenitor of Spemann's organizer. This demonstrates that cells located at the upper blastoporal lip become ventral mesoderm, not solely dorsal mesoderm as previously believed. Reassessment of extant fate maps shows dorsal mesoderm and dorsal endoderm descend from the animal region of the marginal zone, whereas ventral mesoderm descends from the vegetal region of the marginal zone, and ventral endoderm descends from cells located vegetal of the bottle cells. Thus, the orientation of the dorsal-ventral axis of the mesoderm and endoderm is rotated 90(degrees) from its current portrayal in fate maps. This reassessment leads us to propose revisions in the nomenclature of the marginal zone and the orientation of the axes in pre-gastrula Xenopus embryos.

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.

The molecular basis of ciliopathies and cyst formation

2015 ◽  
Author(s):  
Wolfgang Kühn ◽  
Gerd Walz
Keyword(s):  
Planar Cell Polarity ◽  
Critical Role ◽  
Mammalian Target Of Rapamycin ◽  
Renal Cysts ◽  
Cyst Formation ◽  
Cystic Kidney Disease ◽  
Cystic Kidney ◽  
Convergent Extension ◽  
Diverse Range ◽  
Cell Intercalation

Abnormalities of the cilium, termed ‘ciliopathies’, are the prime suspect in the pathogenesis of renal cyst formation because the gene products of cystic disease-causing genes localize to them, or near them. However, we only partially understand how cilia maintain the geometry of kidney tubules, and how abnormal cilia lead to renal cysts, and the diverse range of diseases attributed to them. Some non-cystic diseases share pathology of the same structures. Although still incompletely understood, cilia appear to orient cells in response to extracellular cues to maintain the overall geometry of a tissue, thereby intersecting with the planar cell polarity (PCP) pathway and the actin cytoskeleton. The PCP pathway controls two morphogenetic programmes, oriented cell division (OCD) and convergent extension (CE) through cell intercalation that both seem to play a critical role in cyst formation. The two-hit theory of cystogenesis, by which loss of the second normal allele causes tubular epithelial cells to form kidney cysts, has been largely borne out. Additional hits and influences may better explain the rate of cyst formation and inter-individual differences in disease progression. Ciliary defects appear to converge on overlapping signalling modules, including mammalian target of rapamycin and cAMP pathways, which can be targeted to treat human cystic kidney disease irrespective of the underlying gene mutation.

scholarly journals Molecular and Functional Characterization of Elovl4 Genes in Sparus aurata and Solea senegalensis Pointing to a Critical Role in Very Long-Chain (>C24) Fatty Acid Synthesis during Early Neural Development of Fish

2020 ◽  
Vol 21 (10) ◽  
pp. 3514 ◽  
Author(s):  
Sofia Morais ◽  
Miguel Torres ◽  
Francisco Hontoria ◽  
Óscar Monroig ◽  
Inma Varó ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Neural Development ◽  
Sparus Aurata ◽  
Critical Role ◽  
Functional Characterization ◽  
Acid Synthesis ◽  
Solea Senegalensis ◽  
Preferential Expression ◽  
Neural Tissues ◽  
Long Chain

Very long-chain fatty acids (VLC-FA) play critical roles in neural tissues during the early development of vertebrates. However, studies on VLC-FA in fish are scarce. The biosynthesis of VLC-FA is mediated by elongation of very long-chain fatty acid 4 (Elovl4) proteins and, consequently, the complement and activity of these enzymes determines the capacity that a given species has for satisfying its physiological demands, in particular for the correct development of neurophysiological functions. The present study aimed to characterize and localize the expression of elovl4 genes from Sparus aurata and Solea senegalensis, as well as to determine the function of their encoded proteins. The results confirmed that both fish possess two distinct elovl4 genes, named elovl4a and elovl4b. Functional assays demonstrated that both Elovl4 isoforms had the capability to elongate long-chain (C20–24), both saturated (SFA) and polyunsaturated (PUFA), fatty acid precursors to VLC-FA. In spite of their overlapping activity, Elovl4a was more active in VLC-SFA elongation, while Elovl4b had a preponderant elongation activity towards n-3 PUFA substrates, particularly in S. aurata, being additionally the only isoform that is capable of elongating docosahexaenoic acid (DHA). A preferential expression of elovl4 genes was measured in neural tissues, being elovl4a and elovl4b mRNAs mostly found in brain and eyes, respectively.

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