scholarly journals Microtubules enter centre stage for morphogenesis

2020 ◽  
Vol 375 (1809) ◽  
pp. 20190557 ◽  
Author(s):  
Katja Röper

Cell shape changes are key to observable changes at the tissue level during morphogenesis and organ formation. The major driver of cell shape changes in turn is the actin cytoskeleton, both in the form of protrusive linear or branched dynamic networks and in the form of contractile actomyosin. Over the last 20 years, actomyosin has emerged as the major cytoskeletal system that deforms cells in epithelial sheets during morphogenesis. By contrast, the second major cytoskeletal system, microtubules, have so far mostly been assumed to serve ‘house-keeping' functions, such as directed transport or cell division, during morphogenetic events. Here, I will reflect on a subset of studies over the last 10 years that have clearly shown a major direct role for the microtubule cytoskeleton in epithelial morphogenesis, suggesting that our focus will need to be widened to give more attention and credit to this cytoskeletal system in playing an active morphogenetic role. This article is part of a discussion meeting issue ‘Contemporary morphogenesis'.

2019 ◽  
Author(s):  
Clint S. Ko ◽  
Prateek Kalakuntla ◽  
Adam C. Martin

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.


2006 ◽  
Vol 174 (4) ◽  
pp. 485-490 ◽  
Author(s):  
Chris Janetopoulos ◽  
Peter Devreotes

To perform the vital functions of motility and division, cells must undergo dramatic shifts in cell polarity. Recent evidence suggests that polarized distributions of phosphatidylinositol 4,5-bisphosphate and phosphatidylinositol 3,4,5-trisphosphate, which are clearly important for regulating cell morphology during migration, also play an important role during the final event in cell division, which is cytokinesis. Thus, there is a critical interplay between the membrane phosphoinositides and the cytoskeletal cortex that regulates the complex series of cell shape changes that accompany these two processes.


eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Agnik Dasgupta ◽  
Matthias Merkel ◽  
Madeline J Clark ◽  
Andrew E Jacob ◽  
Jonathan Edward Dawson ◽  
...  

How epithelial cell behaviors are coordinately regulated to sculpt tissue architecture is a fundamental question in biology. Kupffer’s vesicle (KV), a transient organ with a fluid-filled lumen, provides a simple system to investigate the interplay between intrinsic cellular mechanisms and external forces during epithelial morphogenesis. Using 3-dimensional (3D) analyses of single cells we identify asymmetric cell volume changes along the anteroposterior axis of KV that coincide with asymmetric cell shape changes. Blocking ion flux prevents these cell volume changes and cell shape changes. Vertex simulations suggest cell shape changes do not depend on lumen expansion. Consistent with this prediction, asymmetric changes in KV cell volume and shape occur normally when KV lumen growth fails due to leaky cell adhesions. These results indicate ion flux mediates cell volume changes that contribute to asymmetric cell shape changes in KV, and that these changes in epithelial morphology are separable from lumen-generated forces.


2017 ◽  
Author(s):  
Agnik Dasgupta ◽  
Matthias Merkel ◽  
Andrew E. Jacob ◽  
Jonathan Dawson ◽  
M. Lisa Manning ◽  
...  

ABSTRACTHow epithelial cell behaviors are coordinately regulated to sculpt tissue architecture is a fundamental question in biology. Kupffer's vesicle (KV), a transient organ with a fluid - filled lumen, provides a simple system to investigate the interplay between intrinsic cellular mechanisms and external forces during epithelial morphogenesis. Using 3 - dimensional (3D) analyses of single cells we identify asymmetric cell volume changes along the anteroposterior axis of KV that coincide with asymmetric cell shape changes. Blocking ion flux prevents these cell volume changes and cell shape changes. Vertex simulations suggest cell shape changes do not depend on lumen expansion. Consistent with this prediction, asymmetric changes in KV cell volume and shape occur normally when KV lumen growth fails due to leaky cell adhesions. These results indicate ion flux mediates asymmetric cell volume changes that contribute to asymmetric cell shape changes in KV, and that these changes in epithelial morphology are separable from lumen - generated forces.


2020 ◽  
Author(s):  
Joel Dokmegang ◽  
Moi Hoon Yap ◽  
Liangxiu Han ◽  
Matteo Cavaliere ◽  
René Doursat

AbstractUnderstanding the processes by which the mammalian embryo implants in the maternal uterus is a long-standing challenge in embryology. New insights into this morphogenetic event could be of great importance in helping, for example, to reduce human infertility. During implantation the blastocyst, composed of epiblast and trophectoderm, undergoes significant remodelling from an oval ball to an egg cylinder. A main feature of this transformation is symmetry breaking and reshaping of the epiblast into a “cup”. Based on previous studies, we hypothesise that this event is the result of mechanical constraints originating from the trophectoderm, which is also significantly transformed during this process. In order to investigate this hypothesis we propose MG#, an original computational model of biomechanics able to reproduce key cell shape changes and tissue level behaviours in silico. With this model, we simulate epiblast and trophectoderm morphogenesis during implantation. First, our results uphold experimental findings that repulsion at the apical surface of the epiblast is sufficient to drive lumenogenesis. Then, we provide new theoretical evidence that trophectoderm morphogenesis indeed dictates the cup shape of the epiblast and fosters its movement towards the uterine tissue. Together, these results offer mechanical insights into mouse implantation and highlight the usefulness of agent-based modelling methods in the study of embryogenesis.Author summaryComputational modelling is increasingly used in the context of biological development. Here we propose a novel agent-based model of biological cell and tissue mechanics to investigate important morphological changes during mouse embryo implantation. Our model is able to replicate key biological cell shape changes and tissue-level behaviour. Simulating mouse implantation with this model, we bring theoretical support to previous experimental observations that lumenogenesis in the epiblast is driven by repulsion, and provide theoretical evidence that changes in epiblast shape during implantation are regulated by trophectoderm development.


2021 ◽  
Vol 11 (4) ◽  
Author(s):  
Molly C Jud ◽  
Josh Lowry ◽  
Thalia Padilla ◽  
Erin Clifford ◽  
Yuqi Yang ◽  
...  

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.


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