“…To date, a number of theoretical frameworks have been proposed to model lumen growth, focusing either on the early phase of lumen nucleation (see Glossary, Box 1) and coalescence (Dasgupta et al, 2018;Duclut et al, 2019;Dumortier et al, 2019), or on the later phase when the singly resolved lumen undergoes size oscillations (Ruiz-Herrero et al, 2017). A general assumption of these models is that lumen growth is governed by water intake resulting from inward ion transport (for example by sodium-potassium pumps).…”
Section: Lumen Formationmentioning
confidence: 99%
“…However, given recent evidence that the secretion of cytoplasmic vesicles into intercellular space also contributes to microlumina formation (Ryan et al, 2019;Vasquez et al, 2019 preprint), such a mechanism should also be incorporated into future theoretical models. Interestingly, recent theoretical work has shown that ion flows in the fluid can lead to the build up of an electric field across the tissue, the shape of which can, in turn, influence lumen nucleation dynamics and size (Duclut et al, 2019), although this warrants further experimental investigation. Finally, to understand the role of lumen in tissue patterning, future theoretical frameworks must incorporate various feedback interactions between luminal signalling, tissue mechanics and cell fate across multiple spatial and temporal scales.…”
Many developmental processes involve the emergence of intercellular fluid-filled lumina. This process of luminogenesis results in a build up of hydrostatic pressure and signalling molecules in the lumen. However, the potential roles of lumina in cellular functions, tissue morphogenesis and patterning have yet to be fully explored. In this Review, we discuss recent findings that describe how pressurized fluid expansion can provide both mechanical and biochemical cues to influence cell proliferation, migration and differentiation. We also review emerging techniques that allow for precise quantification of fluid pressure in vivo and in situ. Finally, we discuss the intricate interplay between luminogenesis, tissue mechanics and signalling, which provide a new dimension for understanding the principles governing tissue self-organization in embryonic development.
“…To date, a number of theoretical frameworks have been proposed to model lumen growth, focusing either on the early phase of lumen nucleation (see Glossary, Box 1) and coalescence (Dasgupta et al, 2018;Duclut et al, 2019;Dumortier et al, 2019), or on the later phase when the singly resolved lumen undergoes size oscillations (Ruiz-Herrero et al, 2017). A general assumption of these models is that lumen growth is governed by water intake resulting from inward ion transport (for example by sodium-potassium pumps).…”
Section: Lumen Formationmentioning
confidence: 99%
“…However, given recent evidence that the secretion of cytoplasmic vesicles into intercellular space also contributes to microlumina formation (Ryan et al, 2019;Vasquez et al, 2019 preprint), such a mechanism should also be incorporated into future theoretical models. Interestingly, recent theoretical work has shown that ion flows in the fluid can lead to the build up of an electric field across the tissue, the shape of which can, in turn, influence lumen nucleation dynamics and size (Duclut et al, 2019), although this warrants further experimental investigation. Finally, to understand the role of lumen in tissue patterning, future theoretical frameworks must incorporate various feedback interactions between luminal signalling, tissue mechanics and cell fate across multiple spatial and temporal scales.…”
Many developmental processes involve the emergence of intercellular fluid-filled lumina. This process of luminogenesis results in a build up of hydrostatic pressure and signalling molecules in the lumen. However, the potential roles of lumina in cellular functions, tissue morphogenesis and patterning have yet to be fully explored. In this Review, we discuss recent findings that describe how pressurized fluid expansion can provide both mechanical and biochemical cues to influence cell proliferation, migration and differentiation. We also review emerging techniques that allow for precise quantification of fluid pressure in vivo and in situ. Finally, we discuss the intricate interplay between luminogenesis, tissue mechanics and signalling, which provide a new dimension for understanding the principles governing tissue self-organization in embryonic development.
“…Lumina expand either isotropically, yielding spherical structures (acini and alveoli in vivo, cysts and organoids in vitro), or anisotropically, generating a variety of epithelial tube shapes across tissues (e.g., lungs, intestine, kidney, and liver). The anisotropic expansion of lumina is more difficult to explain than the isotropic one because it results from specific combinations of molecular pathways and physical forces ( Datta et al, 2011 ; Navis and Nelson, 2016 ; Jewett and Prekeris, 2018 ; Dasgupta et al, 2018 ; Stopka et al, 2019 ; Duclut et al, 2019 ). Physical forces can act on the tissue or cellular level.…”
Lumen morphogenesis results from the interplay between molecular pathways and mechanical forces. In several organs, epithelial cells share their apical surfaces to form a tubular lumen. In the liver, however, hepatocytes share the apical surface only between adjacent cells and form narrow lumina that grow anisotropically, generating a 3D network of bile canaliculi (BC). Here, by studying lumenogenesis in differentiating mouse hepatoblasts in vitro, we discovered that adjacent hepatocytes assemble a pattern of specific extensions of the apical membrane traversing the lumen and ensuring its anisotropic expansion. These previously unrecognized structures form a pattern, reminiscent of the bulkheads of boats, also present in the developing and adult liver. Silencing of Rab35 resulted in loss of apical bulkheads and lumen anisotropy, leading to cyst formation. Strikingly, we could reengineer hepatocyte polarity in embryonic liver tissue, converting BC into epithelial tubes. Our results suggest that apical bulkheads are cell-intrinsic anisotropic mechanical elements that determine the elongation of BC during liver tissue morphogenesis.
“…One possible explanation for such a pattern would be pulse trains (e.g., muscle clonus [ Hidler and Rymer, 2000 ]), which can indeed be observed in organoid contractions, such as the highlighted region of Figure 3 B. Physical fluidic models of lumen contractility have been proposed ( Duclut et al., 2019 ; Ruiz-Herrero et al., 2017 ) but are not sufficient to predict pulse train or other temporally correlated behavior, suggesting that the contractility phenomenon is biomechanical. Figure 3 Mammary organoids grown in microcontainers exhibit contractility (A) Filmstrips show single contractions of three organoids.…”
Summary
A long-standing constraint on organoid culture is the need to add exogenous substances to provide hydrogel matrix, which limits the study of fully human or fully native organoids. This paper introduces an approach to culture reconstituted mammary organoids without the impediment of exogenous matrix. We enclose organoids in nanoliter-scale, topologically enclosed, fluid compartments surrounded by agar. Organoids cultured in these “microcontainers” appear to secrete enough extracellular matrix to yield a self-sufficient microenvironment without exogenous supplements. In microcontainers, mammary organoids exhibit contractility and a high-level, physiological, myoepithelial (MEP) behavior that has not been previously reported in reconstituted organoids. The presence of contractility suggests that microcontainers elicit MEP functional differentiation, an important milestone. Microcontainers yield thousands of substantially identical and individually trackable organoids within a single culture vessel, enabling longitudinal studies and statistically powerful experiments, such as the evaluation of small effect sizes. Microcontainers open new doors for researchers who rely on organoid models.
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