scholarly journals RhoGAP RGA-8 supports morphogenesis in C. elegans by polarizing epithelia

Biology Open ◽  
2020 ◽  
Vol 9 (11) ◽  
pp. bio056911
Author(s):  
Hamidah Raduwan ◽  
Shashikala Sasidharan ◽  
Luigy Cordova Burgos ◽  
Andre G. Wallace ◽  
Martha C. Soto
Keyword(s):  
Caenorhabditis Elegans ◽  
Cell Shape ◽  
Molecular Data ◽  
Membrane Recruitment ◽  
C Elegans ◽  
Cell Embryo ◽  
Embryonic Morphogenesis ◽  
The One ◽  
Muscle Myosin ◽  
Shape Changes

ABSTRACTCDC-42 regulation of non-muscle myosin/NMY-2 is required for polarity maintenance in the one-cell embryo of Caenorhabditis elegans. CDC-42 and NMY-2 regulate polarity throughout embryogenesis, but their contribution to later events of morphogenesis are less understood. We have shown that epidermal enclosure requires the GTPase CED-10/Rac1 and WAVE/Scar complex, its effector, to promote protrusions that drive enclosure through the branch actin regulator Arp2/3. Our analysis here of RGA-8, a homolog of SH3BP1/Rich1/ARHGAP17/Nadrin, with BAR and RhoGAP motifs, suggests it regulates CDC-42, so that actin and myosin/NMY-2 promote ventral enclosure during embryonic morphogenesis. Genetic and molecular data suggest RGA-8 regulates CDC-42, and phenocopies the CDC-42 pathway regulators WASP-1/WSP-1 and the F-BAR proteins TOCA-1 and TOCA-2. Live imaging shows RGA-8 and WSP-1 enrich myosin and regulate F-actin in migrating epidermal cells during ventral enclosure. Loss of RGA-8 alters membrane recruitment of active CDC-42. We propose TOCA proteins and RGA-8 use BAR domains to localize and regenerate CDC-42 activity, thus regulating F-actin levels, through the branched actin regulator WSP-1, and myosin enrichment. RhoGAP RGA-8 thus polarizes epithelia, to promote cell migrations and cell shape changes of embryonic morphogenesis.

scholarly journals RhoGAP RGA-8 supports morphogenesis in C. elegans by polarizing epithelia through CDC-42

2019 ◽  
Author(s):  
Hamidah Raduwan ◽  
Shashikala Sasidharan ◽  
Luigy Cordova Burgos ◽  
Andre G. Wallace ◽  
Martha C. Soto
Keyword(s):  
Cell Shape ◽  
Control Cell ◽  
Molecular Data ◽  
Regulatory Motifs ◽  
C Elegans ◽  
Cell Embryo ◽  
Embryonic Morphogenesis ◽  
The One ◽  
Muscle Myosin ◽  
Shape Changes

AbstractCDC-42 regulation of non-muscle myosin/NMY-2 is required for polarity maintenance in the one-cell embryo of C. elegans. CDC-42 and NMY-2 regulate polarity throughout embryogenesis, but their contribution to later events of morphogenesis are less understood. We have shown that epidermal enclosure requires the GTPase CED-10/Rac1 and WAVE/Scar complex, its effector, to promote protrusions that drive enclosure through the branch actin regulator Arp2/3. Our analysis here of RGA-8, a homolog of SH3BP1/Rich1/ARHGAP17/Nadrin, with BAR and RhoGAP motifs, suggests it regulates CDC-42, so that NMY-2 promotes two events of epidermal morphogenesis: ventral enclosure and elongation. Genetic and molecular data suggest RGA-8 regulates CDC-42, and the CDC-42 effectors WSP-1 and MRCK-1, in parallel to F-BAR proteins TOCA-1 and TOCA-2. The RGA-8-CDC-42-WSP-1 pathway enriches myosin in migrating epidermal cells during ventral enclosure. We propose TOCA proteins and RGA-8 use BAR domains to localize and regenerate CDC-42 activity, thus regulating F-actin levels, through the branched actin regulator WSP-1, and myosin polarity through the myosin kinase MRCK-1. Regulated CDC-42 thus polarizes epithelia, to control cell migrations and cell shape changes of embryonic morphogenesis.SummaryRGA-8, a protein with membrane binding and actin regulatory motifs, promotes embryonic morphogenesis by localizing active CDC-42 in developing epithelia, thus controlling actin and actin motors during cell movements.

scholarly journals Squeezing an Egg into a Worm: C. elegans Embryonic Morphogenesis

2003 ◽  
Vol 3 ◽  
pp. 1370-1381 ◽  
Author(s):  
A. J. Piekny ◽  
P. E. Mains
Keyword(s):  
Caenorhabditis Elegans ◽  
Epidermal Cells ◽  
Ventral Midline ◽  
Single Row ◽  
C Elegans ◽  
Epithelial Sheet ◽  
Embryonic Morphogenesis ◽  
Shape Changes

We review key morphogenetic events that occur during Caenorhabditis elegans (www.wormbase.org/) embryogenesis. Morphogenesis transforms tissues from one shape into another through cell migrations and shape changes, often utilizing highly conserved actin-based contractile systems. Three major morphogenetic events occur during C. elegans embryogenesis: (1) dorsal intercalation, during which two rows of dorsal epidermal cells intercalate to form a single row; (2) ventral enclosure, where the dorsally located sheet of epidermal cells stretches to the ventral midline, encasing the embryo within a single epithelial sheet; and (3) elongation, during which actin-mediated contractions within the epithelial sheet lengthens the embryo. Here, we describe the known molecular players involved in each of these processes.

scholarly journals A Genetic Screen for Temperature-sensitive Morphogenesis-defective Caenorhabditis elegans Mutants

2020 ◽  
Author(s):  
Molly Christine Jud ◽  
Josh Lowry ◽  
Thalia Padilla ◽  
Erin Clifford ◽  
Yuqi Yang ◽  
...  
Keyword(s):  
Caenorhabditis Elegans ◽  
Epidermal Cell ◽  
Cell Shape ◽  
The Body ◽  
Forward Genetics ◽  
Temperature Sensitive ◽  
Embryonic Lethal ◽  
Embryonic Morphogenesis ◽  
Cell Shape Changes ◽  
Shape Changes

ABSTRACTMorphogenesis involves coordinated cell migrations and cell shape changes that generate tissues and organs, and organize the body plan. Cell adhesion and the cytoskeleton are important for executing morphogenesis, but their regulation remains poorly understood. As genes required for embryonic morphogenesis may have earlier roles in development, temperature-sensitive embryonic-lethal mutations are useful tools for investigating this process. From a collection of ∼200 such Caenorhabditis elegans mutants, we have identified 17 that have highly penetrant embryonic morphogenesis defects after upshifts from the permissive to the restrictive temperature, just prior to the cell shape changes that mediate elongation of the ovoid embryo into a vermiform larva. Using whole genome sequencing, we identified the causal mutations in seven affected genes. These include three genes that have roles in producing the extracellular matrix, which is known to affect the morphogenesis of epithelial tissues in multicellular organisms. The rib-1 and rib-2 genes encode glycosyltransferases, and the emb-9 gene encodes a collagen subunit. We also used live imaging to characterize epidermal cell shape dynamics in one mutant, or1219ts, and observed cell elongation defects during dorsal intercalation and ventral enclosure that may be responsible for the body elongation defects. These results indicate that our screen has identified factors that influence morphogenesis and provides a platform for advancing our understanding of this fundamental biological process.SUMMARYWe performed a systematic, forward genetics screen for temperature-sensitive embryonic-lethal (TS-EL) Caenorhabditis elegans mutants that are specifically defective in embryonic morphogenesis. By taking advantage of temperature-upshifts, we identified several essential genes influencing morphogenesis. We also demonstrated that one mutant has defects in epidermal cell shape changes that likely account for the failure in morphogenesis. The TS-EL mutants we identified will be useful tools for advancing our understanding of the gene networks controlling cell shape changes and movements during morphogenesis.

scholarly journals A genetic screen for temperature-sensitive morphogenesis-defectiveCaenorhabditis elegansmutants

2021 ◽  
Vol 11 (4) ◽  
Author(s):  
Molly C Jud ◽  
Josh Lowry ◽  
Thalia Padilla ◽  
Erin Clifford ◽  
Yuqi Yang ◽  
...  
Keyword(s):  
Cell Shape ◽  
The Body ◽  
Temperature Sensitive ◽  
Restrictive Temperature ◽  
Fundamental Biological Process ◽  
Embryonic Morphogenesis ◽  
Cell Shape Changes ◽  
Development Temperature ◽  
Multicellular Organisms ◽  
Shape Changes

AbstractMorphogenesis involves coordinated cell migrations and cell shape changes that generate tissues and organs, and organize the body plan. Cell adhesion and the cytoskeleton are important for executing morphogenesis, but their regulation remains poorly understood. As genes required for embryonic morphogenesis may have earlier roles in development, temperature-sensitive embryonic-lethal mutations are useful tools for investigating this process. From a collection of ∼200 such Caenorhabditis elegans mutants, we have identified 17 that have highly penetrant embryonic morphogenesis defects after upshifts from the permissive to the restrictive temperature, just prior to the cell shape changes that mediate elongation of the ovoid embryo into a vermiform larva. Using whole genome sequencing, we identified the causal mutations in seven affected genes. These include three genes that have roles in producing the extracellular matrix, which is known to affect the morphogenesis of epithelial tissues in multicellular organisms: the rib-1 and rib-2 genes encode glycosyltransferases, and the emb-9 gene encodes a collagen subunit. We also used live imaging to characterize epidermal cell shape dynamics in one mutant, or1219ts, and observed cell elongation defects during dorsal intercalation and ventral enclosure that may be responsible for the body elongation defects. These results indicate that our screen has identified factors that influence morphogenesis and provides a platform for advancing our understanding of this fundamental biological process.

scholarly journals Coordinated morphogenesis through tension-induced planar polarity

2017 ◽  
Author(s):  
Ghislain Gillard ◽  
Ophélie Nicolle ◽  
Thibault Brugières ◽  
Sylvain Prigent ◽  
Mathieu Pinot ◽  
...  
Keyword(s):  
Cell Shape ◽  
Muscle Contractions ◽  
Developmental Origins ◽  
Planar Polarity ◽  
C Elegans ◽  
Embryonic Tissues ◽  
Cell Shape Changes ◽  
Shape Changes

AbstractTissues from different developmental origins must interact to achieve coordinated morphogenesis at the level of a whole organism. C. elegans embryonic elongation is controlled by actomyosin dynamics which trigger cell shape changes in the epidermis and by muscle contractions, but how the two processes are coordinated is not known. We found that a tissue-wide tension generated by muscle contractions and relayed by tendon-like hemidesmosomes in the dorso-ventral epidermis is required to establish a planar polarity of the apical PAR module in the lateral epidermis. This planar polarized PAR module then controls actin planar organization, thus determining the orientation of cell shape changes and the elongation axis of the whole embryo. This trans-tissular mechanotransduction pathway thus contributes to coordinate the morphogenesis of three embryonic tissues.

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 Centrosome Aurora A gradient ensures a single PAR-2 polarity axis by regulating RhoGEF ECT-2 localization in C. elegans embryos

2018 ◽  
Author(s):  
Sukriti Kapoor ◽  
Sachin Kotak
Keyword(s):  
Spatial Information ◽  
Aurora A Kinase ◽  
Aurora A ◽  
Posterior Cortex ◽  
C Elegans ◽  
Local Inhibition ◽  
Cell Embryo ◽  
Polarity Establishment ◽  
The One ◽  
Cortical Contractility

AbstractThe proper establishment of the cell polarity is essential for development and morphogenesis. In the Caenorhabditis elegans one-cell embryo, a centrosome localized signal provides spatial information that is responsible for generating a single polarity axis. It is hypothesized that such a signal causes local inhibition of cortical actomyosin network in the vicinity of the centrosome. This pivotal event initiates symmetry breaking to direct partitioning of the partition defective proteins (PARs) in the one-cell embryo. However, the molecular nature of the centrosome regulated signal that impinges on the posterior cortex to bring upon cortical anisotropy in the actomyosin network and to promote polarity establishment remains elusive. Here, we discover that Aurora A kinase (AIR-1 in C. elegans) is essential for proper cortical contractility in the one-cell embryo. Loss of AIR-1 causes pronounced cortical contractions on the entire embryo surface during polarity establishment phase, and this creates more than one PAR-2 polarity axis. Moreover, we show that in the absence of AIR-1, centrosome positioning becomes dispensable in dictating the PAR-2 polarity axis. Interestingly, we identify that Rho Guanine Exchange Factor (GEF) ECT-2 acts downstream to AIR-1 to control excess contractility and notably AIR-1 loss affects ECT-2 cortical localization and thereby polarity establishment. Overall, our study unravels a novel insight whereby an evolutionarily conserved kinase Aurora A inhibits promiscuous PAR-2 domain formation and ensures singularity in the polarity establishment axis.

scholarly journals A Putative Catenin–Cadherin System Mediates Morphogenesis of the Caenorhabditis elegans Embryo

1998 ◽  
Vol 141 (1) ◽  
pp. 297-308 ◽  
Author(s):  
Michael Costa ◽  
William Raich ◽  
Cristina Agbunag ◽  
Ben Leung ◽  
Jeff Hardin ◽  
...  
Keyword(s):  
Cell Adhesion ◽  
Caenorhabditis Elegans ◽  
Cell Shape ◽  
Shape Change ◽  
Adherens Junctions ◽  
The Body ◽  
C Elegans ◽  
Cell Shape Change ◽  
Filament Bundles ◽  
Cell Adhesion Proteins

During morphogenesis of the Caenorhabditis elegans embryo, hypodermal (or epidermal) cells migrate to enclose the embryo in an epithelium and, subsequently, change shape coordinately to elongate the body (Priess, J.R., and D.I. Hirsh. 1986. Dev. Biol. 117:156– 173; Williams-Masson, E.M., A.N. Malik, and J. Hardin. 1997. Development [Camb.]. 124:2889–2901). We have isolated mutants defective in morphogenesis that identify three genes required for both cell migration during body enclosure and cell shape change during body elongation. Analyses of hmp-1, hmp-2, and hmr-1 mutants suggest that products of these genes anchor contractile actin filament bundles at the adherens junctions between hypodermal cells and, thereby, transmit the force of bundle contraction into cell shape change. The protein products of all three genes localize to hypodermal adherens junctions in embryos. The sequences of the predicted HMP-1, HMP-2, and HMR-1 proteins are related to the cell adhesion proteins α-catenin, β-catenin/Armadillo, and classical cadherin, respectively. This putative catenin–cadherin system is not essential for general cell adhesion in the C. elegans embryo, but rather mediates specific aspects of morphogenetic cell shape change and cytoskeletal organization.

scholarly journals Cdc42 regulates junctional actin but not cell polarization in the Caenorhabditis elegans epidermis

2017 ◽  
Vol 216 (11) ◽  
pp. 3729-3744 ◽  
Author(s):  
Yuliya Zilberman ◽  
Joshua Abrams ◽  
Dorian C. Anderson ◽  
Jeremy Nance
Keyword(s):  
Caenorhabditis Elegans ◽  
Epidermal Cell ◽  
Cell Shape ◽  
Time Lapse ◽  
Cell Polarization ◽  
Epithelial Morphogenesis ◽  
Actin Organization ◽  
Protein Levels ◽  
Guanosine Triphosphatase ◽  
Shape Changes

During morphogenesis, adherens junctions (AJs) remodel to allow changes in cell shape and position while preserving adhesion. Here, we examine the function of Rho guanosine triphosphatase CDC-42 in AJ formation and regulation during Caenorhabditis elegans embryo elongation, a process driven by asymmetric epidermal cell shape changes. cdc-42 mutant embryos arrest during elongation with epidermal ruptures. Unexpectedly, we find using time-lapse fluorescence imaging that cdc-42 is not required for epidermal cell polarization or junction assembly, but rather is needed for proper junctional actin regulation during elongation. We show that the RhoGAP PAC-1/ARHGAP21 inhibits CDC-42 activity at AJs, and loss of PAC-1 or the interacting linker protein PICC-1/CCDC85A-C blocks elongation in embryos with compromised AJ function. pac-1 embryos exhibit dynamic accumulations of junctional F-actin and an increase in AJ protein levels. Our findings identify a previously unrecognized molecular mechanism for inhibiting junctional CDC-42 to control actin organization and AJ protein levels during epithelial morphogenesis.

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