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.

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 Unipolar distributions of junctional Myosin II identify cell stripe boundaries that drive cell intercalation throughout Drosophila axis extension

eLife ◽  
2016 ◽  
Vol 5 ◽  
Author(s):  
Robert J Tetley ◽  
Guy B Blanchard ◽  
Alexander G Fletcher ◽  
Richard J Adams ◽  
Bénédicte Sanson
Keyword(s):  
Myosin Ii ◽  
Interaction Model ◽  
Cell Interaction ◽  
Cell Number ◽  
Cell Polarization ◽  
Convergence And Extension ◽  
Pair Rule Gene ◽  
Cell Intercalation ◽  
Pair Rule ◽  
Cell Cell

Convergence and extension movements elongate tissues during development. Drosophila germ-band extension (GBE) is one example, which requires active cell rearrangements driven by Myosin II planar polarisation. Here, we develop novel computational methods to analyse the spatiotemporal dynamics of Myosin II during GBE, at the scale of the tissue. We show that initial Myosin II bipolar cell polarization gives way to unipolar enrichment at parasegmental boundaries and two further boundaries within each parasegment, concomitant with a doubling of cell number as the tissue elongates. These boundaries are the primary sites of cell intercalation, behaving as mechanical barriers and providing a mechanism for how cells remain ordered during GBE. Enrichment at parasegment boundaries during GBE is independent of Wingless signaling, suggesting pair-rule gene control. Our results are consistent with recent work showing that a combinatorial code of Toll-like receptors downstream of pair-rule genes contributes to Myosin II polarization via local cell-cell interactions. We propose an updated cell-cell interaction model for Myosin II polarization that we tested in a vertex-based simulation.

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.

Deformation Analyses in Cell and Developmental Biology. Part II—Mechanical Experiments on Cells

1987 ◽  
Vol 109 (1) ◽  
pp. 18-24 ◽  
Author(s):  
L. Y. Cheng
Keyword(s):  
Incompressible Material ◽  
Cell Cortex ◽  
Analysis Method ◽  
Membrane Structures ◽  
Approximate Methods ◽  
Contact Algorithm ◽  
Property Data ◽  
A Cell ◽  
Element Approach

This study employs the finite element approach developed in Part I to analyze mechanical experiments on cells. It views cells as axisymmetric membrane structures containing a body of incompressible material, and models the mechanical contact between a cell and the loading apparatus by a contact algorithm. Since the method is valid for analyzing axisymmetric shell-like bodies with arbitrary shapes, it treates various mechanical experiments on cells in a unified manner. For demonstration purposes, three commonly used mechanical experiments on cells are considered; (1) the compression experiment; (2) the suction (micropipette aspiration) experiment; and (3) the magnetic particle experiment. Based on an estimate of the mechanical property data for unfertilized sea urchin eggs, this analysis method predicts the responses for all three experiments using the same assumptions and approximations. This parallel treatment gives a broad basis for data correlation with experiments. The method also provides insights into mechanical experiments not offered by other approximate methods. For example, it gives the distributions of tensions and stretches on the cell cortex, and suggests the role of friction in the suction experiment.

scholarly journals Cell-cell adhesion regulates Merlin/NF2 interaction with the PAF complex

PLoS ONE ◽  
2021 ◽  
Vol 16 (8) ◽  
pp. e0254697
Author(s):  
Anne E. Roehrig ◽  
Kristina Klupsch ◽  
Juan A. Oses-Prieto ◽  
Selim Chaib ◽  
Stephen Henderson ◽  
...  
Keyword(s):  
Cell Adhesion ◽  
Molecular Mechanisms ◽  
Hippo Pathway ◽  
Contact Inhibition ◽  
Tumour Suppressor ◽  
Cell Cortex ◽  
Dependent Manner ◽  
A Cell ◽  
Cell Cell ◽  
Paf Complex

The PAF complex (PAFC) coordinates transcription elongation and mRNA processing and its CDC73/parafibromin subunit functions as a tumour suppressor. The NF2/Merlin tumour suppressor functions both at the cell cortex and nucleus and is a key mediator of contact inhibition but the molecular mechanisms remain unclear. In this study we have used affinity proteomics to identify novel Merlin interacting proteins and show that Merlin forms a complex with multiple proteins involved in RNA processing including the PAFC and the CHD1 chromatin remodeller. Tumour-derived inactivating mutations in both Merlin and the CDC73 PAFC subunit mutually disrupt their interaction and growth suppression by Merlin requires CDC73. Merlin interacts with the PAFC in a cell density-dependent manner and we identify a role for FAT cadherins in regulating the Merlin-PAFC interaction. Our results suggest that in addition to its function within the Hippo pathway, Merlin is part of a tumour suppressor network regulated by cell-cell adhesion which coordinates post-initiation steps of the transcription cycle of genes mediating contact inhibition.

Morphological polarity of intercalating deep mesodermal cells in the organzer of Xenopus laevis gastrulae

1989 ◽  
Vol 47 ◽  
pp. 840-841
Author(s):  
Ray Keller ◽  
John Shih ◽  
Paul Wilson
Keyword(s):  
Xenopus Laevis ◽  
Time Lapse ◽  
Light Level ◽  
Cell Labelling ◽  
Fluorescent Compound ◽  
Morphogenetic Movements ◽  
Tissue Interactions ◽  
Convergence And Extension ◽  
Morphological Polarity ◽  
Cell Intercalation

The dorsal lip of the blastopore constitutes the “organizer” of the amphibian body plan, both in terms of its tissue interactions and its morphogenetic movements of convergence and extension during gastrulation. This tissue autonomously narrows (converges) and lengthens (extends) during early development, functioning prominently in the morphogenetic movements of both gastrulation and neurulation Xenopus laevis. High resolution time-lapse recording of cell behavior in cultured explants and cell labelling studies have shown that the movements of convergence and extension are produced by radial intercalation of cells, in which several layers rearrange to produce fewer layers of greater area, and by mediolateral intercalation of cells, in which several rows of cells rearrange to produce a narrower, longer array. By labelling individual cells with the fluorescent compound, DiI, and making low light level recordings, we found that cells of the notochord intercalate mediolaterally using polarized protrusive activity at their internal medial or lateral ends. Thus polarized protrusive activity appears to play a major role in mediolateral cell intercalation after the boundary between the notochord and somites forms in the late gastrula stage.We examine further the morphology of the deep mesodermal cells with scanning electron microscopy at earlier stages, to search for morphological manifestations of a similar polarity of protrusive activity. The dorsal deep mesodermal cells of early gastrulae were exposed by rapidly pulling the. epithelial endoderm off the deep cells with forceps, in Danilchik's solution, and fixing the embryo within 15 seconds in 2% glutaraldehyde in 0.1 M sodium cacodylate buffer (pH 7.4) as described previously. The dorsal deep cells adjacent to the epithelium are elongate and aligned parallel to one another and to the circumference of the glastopore (Fig. 1). The medial and lateral ends bear broad, lamelliform protrusions (large pointers, Fig. 1, 2) whereas the anterior and posterior ends bear numerous small filiform protrusions (small pointers, Fig. 1, 2). This characteristic morphology is found only in the dorsal marginal zone, which undergoes convergence and extension by mediolateral intercalation.

The function and mechanism of convergent extension during gastrulation of Xenopus laevis

Development ◽  
1985 ◽  
Vol 89 (Supplement) ◽  
pp. 185-209
Author(s):  
R. E. Keller ◽  
Michael Danilchik ◽  
Robert Gimlich ◽  
John Shih
Keyword(s):  
Marginal Zone ◽  
Cell Formation ◽  
Cell Lineage ◽  
Time Lapse ◽  
Convergent Extension ◽  
A Cell ◽  
Tissue Recombination ◽  
Migration Of Cells ◽  
Time Lapse Video

The processes thought to function in Xenopus gastrulation include bottle cell formation, migration of cells on the roof of the blastocoel, and autonomous convergent extension of the circumblastoporal region. A review of recent and classical results shows that only the last accounts for the bulk of the tissue displacement of gastrulation, including spreading of the marginal zone toward the blastopore, involution of the marginal zone, and closure of the blastopore. Microsurgical manipulation and explantation studies, analysed by time-lapse video and cine microscopy, shows that the dorsal circumblastoporal region contains two regions which show either autonomous or semiautonomous convergent extension. The dorsal involuting marginal zone (IMZ) undergoes convergence (narrowing) and extension (lengthening) after its involution, beginning at the midgastrula stage and continuing through neurulation, such that it simultaneously extends posteriorly across the yolk plug and narrows the blastoporal circumference. Concurrently, the corresponding region of the overlying non-involuting marginal zone (NIMZ) begins a complementary convergent extension, but at a greater rate, which spreads vegetally to occupy surface area vacated by the IMZ. Tissue recombination experiments show that the deep cells of the dorsal IMZ bring about convergent extension. Labelling of small populations of these cells with a cell lineage tracer shows that convergent extension involves intercalation of deep cells to form a longer, narrower array. Direct time-lapse video and cine micrography of deep cells in cultured explants show that convergent extension involves radial and circumferential intercalation. Removal of the entire blastocoel roof of the early gastrula, including all or part of the NIMZ, shows that convergent extension of the IMZ alone can bring about its involution and blastopore closure. The role of convergent extension in gastrulation of other amphibians and other metazoans and its significance to related problems in early development are discussed.

Cell rearrangement and segmentation in Xenopus: direct observation of cultured explants

Development ◽  
1989 ◽  
Vol 105 (1) ◽  
pp. 155-166 ◽  
Author(s):  
P.A. Wilson ◽  
G. Oster ◽  
R. Keller
Keyword(s):  
Explant Culture ◽  
Dorsal Side ◽  
Convergent Extension ◽  
Cell Behaviour ◽  
Cell Rearrangement ◽  
Radial Cell ◽  
Cell Intercalation ◽  
First Time ◽  
The Relationship ◽  
Somitic Mesoderm

We make use of a novel system of explant culture and high resolution video-film recording to analyse for the first time the cell behaviour underlying convergent extension and segmentation in the somitic mesoderm of Xenopus. We find that a sequence of activities sweeps through the somitic mesoderm from anterior to posterior during gastrulation and neurulation, beginning with radial cell intercalation or thinning, continuing with mediolateral intercalation and cell elongation, and culminating in segmentation and somite rotation. Radial intercalation at the posterior tip lengthens the tissue, while mediolateral intercalation farther anterior converges it toward the midline. This extension of the somitic mesoderm helps to elongate the dorsal side of intact neurulae. By separating tissues, we demonstrate that cell rearrangement is independent of the notochord, but radial intercalation - and thus the bulk of extension - requires the presence of an epithelium, either endodermal or ectodermal. Segmentation, on the other hand, can proceed in somitic mesoderm isolated at the end of gastrulation. Finally, we discuss the relationship between cell rearrangement and segmentation.

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