scholarly journals broad controls leg imaginal disc morphogenesis in Drosophila via regulation of cell shape changes and remodeling of extracellular matrix

2019 ◽  
Author(s):  
Clinton Rice ◽  
Stuart Macdonald ◽  
Xiaochen Wang ◽  
Robert E Ward
Keyword(s):  
Extracellular Matrix ◽  
Transcription Factor ◽  
Drosophila Melanogaster ◽  
Cell Shape ◽  
Imaginal Disc ◽  
Molecular Mechanisms ◽  
Matrix Remodeling ◽  
Ecm Remodeling ◽  
Cell Shape Changes ◽  
Shape Changes

AbstractImaginal disc morphogenesis during metamorphosis in Drosophila melanogaster provides an excellent model to uncover molecular mechanisms by which hormonal signals effect physical changes during development. The broad (br) Z2 isoform encodes a transcription factor required for disc morphogenesis in response to 20-hydroxyecdysone, yet how it accomplishes this remains largely unknown. Here, we show that amorphic br5 mutant discs fail to remodel their basal extracellular matrix (ECM) after puparium formation and do not undergo necessary cell shape changes. RNA sequencing of wild type and mutant leg discs identified 717 genes differentially regulated by br; functional studies reveal that several are required for adult leg formation, particularly those involved in remodeling the ECM. Additionally, br Z2 expression is abruptly shut down at the onset of metamorphosis, and expressing it beyond this time results in failure of leg development during the late prepupal and pupal stages. Taken together, our results suggest that br Z2 is required to drive ECM remodeling, change cell shape, and maintain metabolic activity through the mid prepupal stage, but must be switched off to allow expression of pupation genes.Summary StatementThe Drosophila melanogaster ecdysone-responding transcription factor broad controls morphogenetic processes in leg imaginal discs during metamorphosis through regulation of genes involved in extracellular matrix remodeling, metabolism, and cell shape changes and rearrangements.

scholarly journals The Broad Transcription Factor Links Hormonal Signaling, Gene Expression, and Cellular Morphogenesis Events During Drosophila Imaginal Disc Development

Genetics ◽  
2020 ◽  
Vol 216 (4) ◽  
pp. 1137-1152
Author(s):  
Clinton Rice ◽  
Stuart J. Macdonald ◽  
Xiaochen Wang ◽  
Robert E. Ward
Keyword(s):  
Transcription Factor ◽  
Cell Shape ◽  
Imaginal Disc ◽  
Molecular Mechanisms ◽  
Ecm Remodeling ◽  
Functional Studies ◽  
Link Type ◽  
Leg Development ◽  
Puparium Formation ◽  
Physical Changes

Imaginal disc morphogenesis during metamorphosis in Drosophila melanogaster provides an excellent model to uncover molecular mechanisms by which hormonal signals effect physical changes during development. The broad (br) Z2 isoform encodes a transcription factor required for disc morphogenesis in response to 20-hydroxyecdysone, yet how it accomplishes this remains largely unknown. Here, we use functional studies of amorphic br5 mutants and a transcriptional target approach to identify processes driven by br and its regulatory targets in leg imaginal discs. br5 mutants fail to properly remodel their basal extracellular matrix (ECM) between 4 and 7 hr after puparium formation. Additionally, br5 mutant discs do not undergo the cell shape changes necessary for leg elongation and fail to elongate normally when exposed to the protease trypsin. RNA-sequencing of wild-type and br5 mutant leg discs identified 717 genes differentially regulated by br, including a large number of genes involved in glycolysis, and genes that encode proteins that interact with the ECM. RNA interference-based functional studies reveal that several of these genes are required for adult leg formation, particularly those involved in remodeling the ECM. Additionally, br Z2 expression is abruptly shut down at the onset of metamorphosis, and expressing it beyond this time results in failure of leg development during the late prepupal and pupal stages. Taken together, our results suggest that br Z2 is required to drive ECM remodeling, change cell shape, and maintain metabolic activity through the midprepupal stage, but must be switched off to allow expression of pupation genes.

scholarly journals Integrin binding and cell spreading on extracellular matrix act at different points in the cell cycle to promote hepatocyte growth.

1994 ◽  
Vol 5 (9) ◽  
pp. 967-975 ◽  
Author(s):  
L K Hansen ◽  
D J Mooney ◽  
J P Vacanti ◽  
D E Ingber
Keyword(s):  
Cell Cycle ◽  
Extracellular Matrix ◽  
Cell Shape ◽  
Time Course ◽  
Cell Spreading ◽  
S Phase ◽  
Similar Time ◽  
Cell Shape Changes ◽  
Hepatocyte Growth ◽  
Shape Changes

This study was undertaken to determine the importance of integrin binding and cell shape changes in the control of cell-cycle progression by extracellular matrix (ECM). Primary rat hepatocytes were cultured on ECM-coated dishes in serum-free medium with saturating amounts of growth factors (epidermal growth factor and insulin). Integrin binding and cell spreading were promoted in parallel by plating cells on dishes coated with fibronectin (FN). Integrin binding was separated from cell shape changes by culturing cells on dishes coated with a synthetic arg-gly-asp (RGD)-peptide that acts as an integrin ligand but does not support hepatocyte extension. Expression of early (junB) and late (ras) growth response genes and DNA synthesis were measured to determine whether these substrata induce G0-synchronized hepatocytes to reenter the growth cycle. Cells plated on FN exhibited transient increases in junB and ras gene expression (within 2 and 8 h after plating, respectively) and synchronous entry into S phase. Induction of junB and ras was observed over a similar time course in cells on RGD-coated dishes, however, these round cells did not enter S phase. The possibility that round cells on RGD were blocked in mid to late G1 was confirmed by the finding that when trypsinized and replated onto FN-coated dishes after 30 h of culture, they required a similar time (12-15 h) to reenter S phase as cells that had been spread and allowed to progress through G1 on FN. We have previously shown that hepatocytes remain viable and maintain high levels of liver-specific functions when cultured on these RGD-coated dishes. Thus, these results suggest that ECM acts at two different points in the cell cycle to regulate hepatocyte growth: first, by activating the G0/G1 transition via integrin binding and second, by promoting the G1/S phase transition and switching off the default differentiation program through mechanisms related to cell spreading.

scholarly journals Orchestrating morphogenesis: building the body plan by cell shape changes and movements

Development ◽  
2020 ◽  
Vol 147 (17) ◽  
pp. dev191049 ◽  
Author(s):  
Kia Z. Perez-Vale ◽  
Mark Peifer
Keyword(s):  
Cell Shape ◽  
Molecular Mechanisms ◽  
Fruit Fly ◽  
Body Plan ◽  
The Body ◽  
Collective Cell Migration ◽  
Convergent Extension ◽  
Apical Constriction ◽  
Cell Shape Changes ◽  
Shape Changes

ABSTRACTDuring embryonic development, a simple ball of cells re-shapes itself into the elaborate body plan of an animal. This requires dramatic cell shape changes and cell movements, powered by the contractile force generated by actin and myosin linked to the plasma membrane at cell-cell and cell-matrix junctions. Here, we review three morphogenetic events common to most animals: apical constriction, convergent extension and collective cell migration. Using the fruit fly Drosophila as an example, we discuss recent work that has revealed exciting new insights into the molecular mechanisms that allow cells to change shape and move without tearing tissues apart. We also point out parallel events at work in other animals, which suggest that the mechanisms underlying these morphogenetic processes are conserved.

scholarly journals The plastic cell: mechanical deformation of cells and tissues

Open Biology ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 210006
Author(s):  
Kelly Molnar ◽  
Michel Labouesse
Keyword(s):  
Cell Shape ◽  
Molecular Mechanisms ◽  
Magnetic Beads ◽  
Embryonic Cell ◽  
Permanent Cell ◽  
Experimental Approaches ◽  
Cell Shape Changes ◽  
Actin Remodelling ◽  
Fine Tune ◽  
Shape Changes

Epithelial cells possess the ability to change their shape in response to mechanical stress by remodelling their junctions and their cytoskeleton. This property lies at the heart of tissue morphogenesis in embryos. A key feature of embryonic cell shape changes is that they result from repeated mechanical inputs that make them partially irreversible at each step. Past work on cell rheology has rarely addressed how changes can become irreversible in a complex tissue. Here, we review new and exciting findings dissecting some of the physical principles and molecular mechanisms accounting for irreversible cell shape changes. We discuss concepts of mechanical ratchets and tension thresholds required to induce permanent cell deformations akin to mechanical plasticity. Work in different systems has highlighted the importance of actin remodelling and of E-cadherin endocytosis. We also list some novel experimental approaches to fine-tune mechanical tension, using optogenetics, magnetic beads or stretching of suspended epithelial tissues. Finally, we discuss some mathematical models that have been used to describe the quantitative aspects of accounting for mechanical cell plasticity and offer perspectives on this rapidly evolving field.

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.

Sign in / Sign up

Export Citation Format

Share Document