scholarly journals Abl suppresses cell extrusion and intercalation during epithelium folding

2016 ◽  
Vol 27 (18) ◽  
pp. 2822-2832 ◽  
Author(s):  
Jeanne N. Jodoin ◽  
Adam C. Martin
Keyword(s):  
Cell Shape ◽  
Epithelial To Mesenchymal Transition ◽  
Adherens Junction ◽  
Apical Constriction ◽  
Mesenchymal Transition ◽  
Abl Tyrosine Kinase ◽  
Cell Intercalation ◽  
Shape Changes ◽  
Insight Into ◽  
Cell Extrusion

Tissue morphogenesis requires control over cell shape changes and rearrangements. In the Drosophila mesoderm, linked epithelial cells apically constrict, without cell extrusion or intercalation, to fold the epithelium into a tube that will then undergo epithelial-to-mesenchymal transition (EMT). Apical constriction drives tissue folding or cell extrusion in different contexts, but the mechanisms that dictate the specific outcomes are poorly understood. Using live imaging, we found that Abelson (Abl) tyrosine kinase depletion causes apically constricting cells to undergo aberrant basal cell extrusion and cell intercalation. abl depletion disrupted apical–basal polarity and adherens junction organization in mesoderm cells, suggesting that extruding cells undergo premature EMT. The polarity loss was associated with abnormal basolateral contractile actomyosin and Enabled (Ena) accumulation. Depletion of the Abl effector Enabled (Ena) in abl-depleted embryos suppressed the abl phenotype, consistent with cell extrusion resulting from misregulated ena. Our work provides new insight into how Abl loss and Ena misregulation promote cell extrusion and EMT.

scholarly journals Neuralized regulates a travelling wave of Epithelium-to-Neural Stem Cell morphogenesis in Drosophila

2020 ◽  
Author(s):  
Chloé Shard ◽  
Juan Luna-Escalante ◽  
François Schweisguth
Keyword(s):  
Stem Cells ◽  
Ubiquitin Ligase ◽  
Epithelial To Mesenchymal Transition ◽  
Optic Lobe ◽  
E3 Ubiquitin Ligase ◽  
Tissue Level ◽  
Travelling Wave ◽  
Cell Morphogenesis ◽  
Apical Constriction ◽  
Mesenchymal Transition

AbstractMany tissues are produced during development by specialized progenitor cells emanating from epithelia via an Epithelial-to-Mesenchymal Transition (EMT). Most studies have so far focused on cases involving single or isolated groups of cells. Here we describe an EMT-like process that requires tissue level coordination. This EMT-like process occurs along a continuous front in the Drosophila optic lobe neuroepithelium to produce neural stem cells (NSCs). We find that emerging NSCs remain epithelial and apically constrict before dividing asymmetrically to produce neurons. Apical constriction is associated with contractile myosin pulses and requires the E3 ubiquitin ligase Neuralized and RhoGEF3. Neuralized down-regulates the apical protein Crumbs via its interaction with Stardust. Disrupting the regulation of Crumbs by Neuralized led to defects in apical constriction and junctional myosin accumulation, and to imprecision in the integration of emerging NSCs into the transition front. Neuralized therefore appears to mechanically couple NSC fate acquisition with cell-cell rearrangement to promote smooth progression of the differentiation front.

scholarly journals Apical Constriction Reversal upon Mitotic Entry Underlies Different Morphogenetic Outcomes of Cell Division

2019 ◽  
Author(s):  
Clint S. Ko ◽  
Prateek Kalakuntla ◽  
Adam C. Martin
Keyword(s):  
Cell Division ◽  
Cell Shape ◽  
Mitotic Cell ◽  
Signal Interference ◽  
Apical Constriction ◽  
Mitotic Entry ◽  
Cell Divisions ◽  
Cell Shape Changes ◽  
Shape Changes ◽  
Mitotic Cells

AbstractDuring development, coordinated cell shape changes and cell divisions sculpt tissues. While these individual cell behaviors have been extensively studied, how cell shape changes and cell divisions that occur concurrently in epithelia influence tissue shape is less understood. We addressed this question in two contexts of the early Drosophila embryo: premature cell division during mesoderm invagination, and native ectodermal cell divisions with ectopic activation of apical contractility. Using quantitative live-cell imaging, we demonstrated that mitotic entry reverses apical contractility by interfering with medioapical RhoA signaling. While premature mitotic entry inhibits mesoderm invagination, which relies on apical constriction, mitotic entry in an artificially contractile ectoderm induced ectopic tissue invaginations. Ectopic invaginations resulted from medioapical myosin loss in neighboring mitotic cells. This myosin loss enabled non-mitotic cells to apically constrict through mitotic cell stretching. Thus, the spatial pattern of mitotic entry can differentially regulate tissue shape through signal interference between apical contractility and mitosis.

scholarly journals Using Bcr-Abl to Examine Mechanisms by Which Abl Kinase Regulates Morphogenesis in Drosophila

2008 ◽  
Vol 19 (1) ◽  
pp. 378-393 ◽  
Author(s):  
Traci L. Stevens ◽  
Edward M. Rogers ◽  
Laura M. Koontz ◽  
Donald T. Fox ◽  
Catarina C.F. Homem ◽  
...  
Keyword(s):  
Cell Shape ◽  
Normal Development ◽  
Wild Type ◽  
Nonreceptor Tyrosine Kinase ◽  
Abl Kinase ◽  
Embryonic Morphogenesis ◽  
Dose Dependent ◽  
Shape Changes ◽  
Insight Into

Signaling by the nonreceptor tyrosine kinase Abelson (Abl) plays key roles in normal development, whereas its inappropriate activation helps trigger the development of several forms of leukemia. Abl is best known for its roles in axon guidance, but Abl and its relatives also help regulate embryonic morphogenesis in epithelial tissues. Here, we explore the role of regulation of Abl kinase activity during development. We first compare the subcellular localization of Abl protein and of active Abl, by using a phosphospecific antibody, providing a catalog of places where Abl is activated. Next, we explore the consequences for morphogenesis of overexpressing wild-type Abl or expressing the activated form found in leukemia, Bcr-Abl. We find dose-dependent effects of elevating Abl activity on morphogenetic movements such as head involution and dorsal closure, on cell shape changes, on cell protrusive behavior, and on the organization of the actin cytoskeleton. Most of the effects of Abl activation parallel those caused by reduction in function of its target Enabled. Abl activation leads to changes in Enabled phosphorylation and localization, suggesting a mechanism of action. These data provide new insight into how regulated Abl activity helps direct normal development and into possible biological functions of Bcr-Abl.

scholarly journals Integration of contractile forces during tissue invagination

2010 ◽  
Vol 188 (5) ◽  
pp. 735-749 ◽  
Author(s):  
Adam C. Martin ◽  
Michael Gelbart ◽  
Rodrigo Fernandez-Gonzalez ◽  
Matthias Kaschube ◽  
Eric F. Wieschaus
Keyword(s):  
Cell Shape ◽  
Control Cell ◽  
Adherens Junction ◽  
Tissue Level ◽  
Epithelial Morphogenesis ◽  
Apical Constriction ◽  
Contractile Forces ◽  
Actomyosin Cytoskeleton ◽  
Cellular Forces ◽  
Anterior Posterior

Contractile forces generated by the actomyosin cytoskeleton within individual cells collectively generate tissue-level force during epithelial morphogenesis. During Drosophila mesoderm invagination, pulsed actomyosin meshwork contractions and a ratchet-like stabilization of cell shape drive apical constriction. Here, we investigate how contractile forces are integrated across the tissue. Reducing adherens junction (AJ) levels or ablating actomyosin meshworks causes tissue-wide epithelial tears, which release tension that is predominantly oriented along the anterior–posterior (a-p) embryonic axis. Epithelial tears allow cells normally elongated along the a-p axis to constrict isotropically, which suggests that apical constriction generates anisotropic epithelial tension that feeds back to control cell shape. Epithelial tension requires the transcription factor Twist, which stabilizes apical myosin II, promoting the formation of a supracellular actomyosin meshwork in which radial actomyosin fibers are joined end-to-end at spot AJs. Thus, pulsed actomyosin contractions require a supracellular, tensile meshwork to transmit cellular forces to the tissue level during morphogenesis.

scholarly journals Cell intercalation driven by SMAD3 underlies secondary neural tube formation

2020 ◽  
Author(s):  
Elena Gonzalez-Gobartt ◽  
José Blanco-Ameijeiras ◽  
Susana Usieto ◽  
Guillaume Allio ◽  
Bertrand Benazeraf ◽  
...  
Keyword(s):  
Neural Tube ◽  
Epithelial To Mesenchymal Transition ◽  
De Novo ◽  
Tube Formation ◽  
List Type ◽  
Lumen Formation ◽  
Mesenchymal Transition ◽  
Cell Intercalation ◽  
Neural Tube Formation

SUMMARYBody axis elongation is a hallmark of the vertebrate embryo, involving the architectural remodelling of the tailbud. Although it is clear how bi-potential neuro-mesodermal progenitors (NMPs) contribute to embryo elongation, the dynamic events that lead to de novo lumen formation and that culminate in the formation of a 3-Dimensional, secondary neural tube from NMPs, are poorly understood. Here, we used in vivo imaging of the chicken embryo to show that cell intercalation downstream of TGF-beta/SMAD3 signalling is required for secondary neural tube formation. Our analysis describes the initial events in embryo elongation including lineage restriction, the epithelial-to-mesenchymal transition of NMPs, and the initiation of lumen formation. Importantly, we show that the resolution of a single, centrally positioned continuous lumen, which occurs through the intercalation of central cells, requires SMAD3 activity. We anticipate that these findings will be relevant to understand caudal, skin-covered neural tube defects, amongst the most frequent birth defects detected in humans.HIGHLIGHTS.- Initiation of the lumen formation follows the acquisition of neural identity and epithelial polarization..- Programmed cell death is not required for lumen resolution..- Resolution of a single central lumen requires cell intercalation, driven by Smad3 activity.- The outcome of central cell division preceding cell intercalation, varies along the cranio-caudal axis.

How do sea urchins invaginate? Using biomechanics to distinguish between mechanisms of primary invagination

Development ◽  
1995 ◽  
Vol 121 (7) ◽  
pp. 2005-2018 ◽  
Author(s):  
L.A. Davidson ◽  
M.A. Koehl ◽  
R. Keller ◽  
G.F. Oster
Keyword(s):  
Mechanical Properties ◽  
Extracellular Matrix ◽  
Finite Element ◽  
Cell Shape ◽  
Sea Urchins ◽  
Specific Cell ◽  
Apical Constriction ◽  
Epithelial Sheet ◽  
Shape Changes ◽  
Design Experiments

The forces that drive sea urchin primary invagination remain mysterious. To solve this mystery we have developed a set of finite element simulations that test five hypothesized mechanisms. Our models show that each of these mechanisms can generate an invagination; however, the mechanical properties of an epithelial sheet required for proper invagination are different for each mechanism. For example, we find that the gel swelling hypothesis of Lane et al. (Lane, M. C., Koehl, M. A. R., Wilt, F. and Keller, R. (1993) Development 117, 1049–1060) requires the embryo to possess a mechanically stiff apical extracellular matrix and highly deformable cells, whereas a hypothesis based on apical constriction of the epithelial cells requires a more compliant extracellular matrix. For each mechanism, we have mapped out a range of embryo designs that work. Additionally, the simulations predict specific cell shape changes accompanying each mechanism. This allows us to design experiments that can distinguish between different mechanisms, all of which can, in principle, drive primary invagination.

scholarly journals CRB3A Controls the Morphology and Cohesion of Cancer Cells through Ehm2/p114RhoGEF-Dependent Signaling

2015 ◽  
Vol 35 (19) ◽  
pp. 3423-3435 ◽  
Author(s):  
Elise Loie ◽  
Lucie E. Charrier ◽  
Kévin Sollier ◽  
Jean-Yves Masson ◽  
Patrick Laprise
Keyword(s):  
Epithelial Cell ◽  
Cancer Cells ◽  
Hela Cells ◽  
Cell Shape ◽  
Molecular Mechanisms ◽  
Epithelial To Mesenchymal Transition ◽  
Transmembrane Protein ◽  
Cell Polarization ◽  
Cell Periphery ◽  
Mesenchymal Transition

The transmembrane protein CRB3A controls epithelial cell polarization. Elucidating the molecular mechanisms of CRB3A function is essential as this protein prevents the epithelial-to-mesenchymal transition (EMT), which contributes to tumor progression. To investigate the functional impact of altered CRB3A expression in cancer cells, we expressed CRB3A in HeLa cells, which are devoid of endogenous CRB3A. While control HeLa cells display a patchy F-actin distribution, CRB3A-expressing cells form a circumferential actomyosin belt. This reorganization of the cytoskeleton is accompanied by a transition from an ameboid cell shape to an epithelial-cell-like morphology. In addition, CRB3A increases the cohesion of HeLa cells. To perform these functions, CRB3A recruits p114RhoGEF and its activator Ehm2 to the cell periphery using both functional motifs of its cytoplasmic tail and increases RhoA activation levels. ROCK1 and ROCK2 (ROCK1/2), which are critical effectors of RhoA, are also essential to modulate the cytoskeleton and cell shape downstream of CRB3A. Overall, our study highlights novel roles for CRB3A and deciphers the signaling pathway conferring to CRB3A the ability to fulfill these functions. Thereby, our data will facilitate further investigation of CRB3A functions and increase our understanding of the cellular defects associated with the loss of CRB3A expression in cancer cells.

scholarly journals DIPA-family coiled-coils bind conserved isoform-specific head domain of p120-catenin family: potential roles in hydrocephalus and heterotopia

2014 ◽  
Vol 25 (17) ◽  
pp. 2592-2603 ◽  
Author(s):  
Nicholas O. Markham ◽  
Caleb A. Doll ◽  
Michael R. Dohn ◽  
Rachel K. Miller ◽  
Huapeng Yu ◽  
...  
Keyword(s):  
Epithelial To Mesenchymal Transition ◽  
Specific Binding ◽  
Protein A ◽  
Family Members ◽  
Adherens Junction ◽  
Dependent Manner ◽  
Interacting Protein ◽  
P120 Catenin ◽  
Mesenchymal Transition ◽  
Head Domain

p120-catenin (p120) modulates adherens junction (AJ) dynamics by controlling the stability of classical cadherins. Among all p120 isoforms, p120-3A and p120-1A are the most prevalent. Both stabilize cadherins, but p120-3A is preferred in epithelia, whereas p120-1A takes precedence in neurons, fibroblasts, and macrophages. During epithelial-to-mesenchymal transition, E- to N-cadherin switching coincides with p120-3A to -1A alternative splicing. These isoforms differ by a 101–amino acid “head domain” comprising the p120-1A N-terminus. Although its exact role is unknown, the head domain likely mediates developmental and cancer-associated events linked to p120-1A expression (e.g., motility, invasion, metastasis). Here we identified delta-interacting protein A (DIPA) as the first head domain–specific binding partner and candidate mediator of isoform 1A activity. DIPA colocalizes with AJs in a p120-1A- but not 3A-dependent manner. Moreover, all DIPA family members (Ccdc85a, Ccdc85b/DIPA, and Ccdc85c) interact reciprocally with p120 family members (p120, δ-catenin, p0071, and ARVCF), suggesting significant functional overlap. During zebrafish neural tube development, both knockdown and overexpression of DIPA phenocopy N-cadherin mutations, an effect bearing functional ties to a reported mouse hydrocephalus phenotype associated with Ccdc85c. These studies identify a novel, highly conserved interaction between two protein families that may participate either individually or collectively in N-cadherin–mediated development.

scholarly journals Hyperactivation of the folded gastrulation pathway induces specific cell shape changes

Development ◽  
1998 ◽  
Vol 125 (4) ◽  
pp. 589-597 ◽  
Author(s):  
P. Morize ◽  
A.E. Christiansen ◽  
M. Costa ◽  
S. Parks ◽  
E. Wieschaus
Keyword(s):  
Cell Shape ◽  
Inducible Promoter ◽  
Specific Cell ◽  
Apical Surface ◽  
Apical Constriction ◽  
Cellular Effects ◽  
Ventral Furrow ◽  
Cell Shape Changes ◽  
Shape Changes

During Drosophila gastrulation, mesodermal precursors are brought into the interior of the embryo by formation of the ventral furrow. The first steps of ventral furrow formation involve a flattening of the apical surface of the presumptive mesodermal cells and a constriction of their apical diameters. In embryos mutant for folded gastrulation (fog), these cell shape changes occur but the timing and synchrony of the constrictions are abnormal. A similar phenotype is seen in a maternal effect mutant, concertina (cta). fog encodes a putative secreted protein whereas cta encodes an (alpha)-subunit of a heterotrimeric G protein. We have proposed that localized expression of the fog signaling protein induces apical constriction by interacting with a receptor whose downstream cellular effects are mediated by the cta G(alpha)protein. <P> In order to test this model, we have ectopically expressed fog at the blastoderm stage using an inducible promoter. In addition, we have examined the constitutive activation of cta protein by blocking GTP hydrolysis using both in vitro synthesized mutant alleles and cholera toxin treatment. Activation of the fog/cta pathway by any of these procedures results in ectopic cell shape changes in the gastrula. Uniform fog expression rescues the gastrulation defects of fog null embryos but not cta mutant embryos, arguing that cta functions downstream of fog expression. The normal location of the ventral furrow in embryos with uniformly expressed fog suggests the existence of a fog-independent pathway determining mesoderm-specific cell behaviors and invagination. Epistasis experiments indicate that this pathway requires snail but not twist expression.

scholarly journals Microtubules stabilize intercellular contractile force transmission during tissue folding

2019 ◽  
Author(s):  
Clint S. Ko ◽  
Vardges Tserunyan ◽  
Adam C. Martin
Keyword(s):  
Cell Shape ◽  
Adherens Junctions ◽  
Adherens Junction ◽  
Contractile Force ◽  
Force Transmission ◽  
Microtubule Network ◽  
Apical Constriction ◽  
Actomyosin Contractility ◽  
Actomyosin Contraction ◽  
Stable Connection

AbstractDuring development, forces transmitted between cells are critical for sculpting epithelial tissues. Actomyosin contractility in the middle of the cell apex (medioapical) can change cell shape (e.g., apical constriction), but can also result in force transmission between cells via attachments to adherens junctions. How actomyosin networks maintain attachments to adherens junctions under tension is poorly understood. Here, we discovered that microtubules stabilize actomyosin intercellular attachments in epithelia during Drosophila mesoderm invagination. First, we used live imaging to show a novel arrangement of the microtubule cytoskeleton during apical constriction: medioapical, non-centrosomal Patronin (CAMSAP) foci formed by actomyosin contraction organizes an apical microtubule network. Microtubules were required for mesoderm invagination but were not necessary for apical contractility or adherens junction assembly. Instead, microtubules promoted the stable connection between medioapical actomyosin and adherens junctions. These results define a role for coordination between actin and microtubule cytoskeletal systems in intercellular force transmission and tissue morphogenesis.

Sign in / Sign up

Export Citation Format

Share Document