# Epithelium morphogenesis: Getting the right shape by (re)orienting growth

Vincent Mirouse

► To cite this version:

Vincent Mirouse. Epithelium morphogenesis: Getting the right shape by (re)orienting growth. Current Biology, 2025, 35 (14), pp.R713-R715. 10.1016/j.cub.2025.06.021. hal-05336756

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Submitted on 29 Oct 2025

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# Epithelium morphogenesis: getting the right shape by (re)orienting growth

Vincent Mirouse

Université Clermont Auvergne, Institute of Genetics, Reproduction and Development (iGReD),
UMR CNRS 6293-INSERM U1103, Faculté de Médecine, Clermont-Ferrand, France.

Vincent.mirouse@uca.fr

**Summary:** How animal morphogenesis is coupled with growth is not yet well understood. A new study explains how the fly retina develops, showing an initial phase of tissue curvature and planar expansion, and a second phase of thickening associated with growth along the apical-basal axis.

The shape of cells and tissues often reflects functional requirements. The *Drosophila* retina exemplifies this: on the one hand, its curved shape allows photoreceptor cells to point in different directions, optimizing environmental perception. On the other hand, the thickness of the retina, driven by cell elongation along the apical-basal axis, is essential for the complex architecture of the ommatidia and the functional specialization of neuroepithelial photoreceptor cells. A new study sheds light on the morphogenesis of this structure and highlights how growth and morphogenesis are coordinated¹.

In plants, where cells are confined by rigid walls and cannot migrate or change their respective position, morphogenetic processes are intrinsically tied to the spatiotemporal control of growth ². In contrast, in animals, our understanding of morphogenesis is largely twisted by model systems where growth is not a dominant factor—either because the tissue is not undergoing growth (i.e. volume increase and not only cell divisions), or because the morphogenetic process occurs too quickly for growth to play a significant role. These biases are understandable: fast processes (minutes to a few hours) are easier to capture live under the microscope, and the absence of growth simplifies the mechanical landscape, facilitating mechanistic dissection. Nevertheless, it is increasingly clear that during animal development, growth and morphogenesis must be tightly coordinated and studied as interdependent processes.

The study by Lancaster et al. is valuable in several respects. First, it follows the development of the *Drosophila* retina during metamorphosis using intravital imaging with light-sheet microscopy. Crucially, this technique allows for live imaging over several tens of hours—a time window compatible with tissue growth, especially in a fast-developing organism like the fly. Second, the authors developed a 2D vertex model that makes predictions about the mechanical parameters driving retinal morphogenesis, which they test experimentally.

Fly retina is composed of about 750 ommatidia, each regrouping 20 cells including 8 photoreceptors cells, with an extremely stereotyped organization (Figure 1A). This pseudo-crystalline organization has fascinated developmental biologists since decades. However, the dynamics of the whole tissue during metamorphosis was less described and understood. Lancaster et al. address this gap. If considering the whole retina as a simple epithelial sheet, the overall developmental sequence described is rather straightforward (Figure 1B). The retina
initially appears as a flat epithelium composed of nearly cuboidal cells. Over the next 30 hours, two key events occur: a doubling of the planar area and a marked increase in tissue curvature, with the apical side bulging outward. Over the following 50 hours, the tissue thickens significantly (by about 5 times), which coincides with a strong reduction in basal surface area. This suggests a clear two-step process.

The authors first investigated how curvature arises during the initial phase. Understanding epithelial curvature is a classic problem in morphogenesis, relevant to processes such as invagination, folding or tube formation. Traditionally, curvature is attributed to a tension differential between the apical and basal poles of epithelial cells, often involving increased tension at one pole ³⁻⁶. What makes this case interesting is that curvature occurs simultaneously with planar expansion. Using their vertex model—manipulating apical, basal, and lateral tension as well as cell size—the authors identified parameter combinations giving a shape matching the in vivo observations. Interestingly, the model suggests that curvature arises from a relatively larger decrease in apical tension compared to basal tension. Importantly, configurations involving increased cortical tension could not support the observed planar expansion. However, experimental validation of this model remains limited. Instead, the authors provide indirect evidence for an alternative force due to the hemolymph, the circulatory fluid that bathes internal tissues. They show that if is allowed to leak, retinal shape becomes irregular, resembling mechanical buckling seen in other systems undergoing planar growth and with fixed boundaries ⁶,⁷. This implies that the mechanical bias shaping curvature may be extrinsic, due to hydrostatic pressure of the hemolymph pushing outwards. Still, the low cortical tension predicted by the model (and supported by laser ablation experiments for the basal domain) would facilitate both curvature and expansion under pressure (Figure 1B).

The authors then turned to the second phase: tissue thickening. Modeling again pointed to an increase in cell size—i.e., cell growth—as a prerequisite. Two scenarios could account for apical-basal elongation and the final shape of the retina: either a decrease in lateral tension or an increase in basal tension. Evidence from other systems, such as the zebrafish retina, suggests lateral tension modulation often plays a role in controlling cell height ⁸,⁹. However, in this study, several lines of evidence support the importance of basal tension (Figure 1B). First, in silico modeling produced more realistic kinetics when basal tension was increased. Second, laser ablation experiments revealed significantly higher basal cortical tension during the thickening phase than during the curvature phase. Finally, time- and tissue-specific genetic perturbations further supported this conclusion. Targeting Myosin II (the key driver of cortical tension) or integrins (which mediate adhesion to the basal extracellular matrix) led to reduced basal tension and a corresponding reduction in retinal thickening.

Together, these findings provide a coherent model for retinal morphogenesis. The two observed phases—planar expansion with curvature and apical-basal thickening—appear to require opposite mechanical regimes, particularly at the basal domain. This suggests they must occur sequentially. The question then arises: what drives the transition between the two?
As shown here and in prior work from the same team, the transition coincides with a striking reorganization of the basal cytoskeleton<sup>10</sup>. Of note, in ommatidia, not all the cells are equivalent, though they are considered as so in authors' models, and this assertion is also true for their basal domain. Each ommatidium assembles a star-shaped network of F-actin. This process involves a complex cascade: the Dystroglycan-Dystrophin complex is recruited, followed by remodeling of the basement membrane and polarized recruitment of integrins. The resulting networks resemble stress fibers and, laser ablation reveals that they are under high tension. Moreover, star branches, made of these stress fibers, appear interconnected between ommatidia, suggesting that they form a supracellular, isotropic, contractile meshwork. This reorganization thus marks a mechanical switch: from a compliant, pressure-sensitive tissue to a contractile, tension-bearing structure. Interestingly, such supracellular basal networks, either isotropic or anisotropic, are now emerging as a common feature of epithelial tissues and may serve as key organizers of tissue-scale morphogenesis<sup>11,12</sup>.

In conclusion, this study offers new insights into how growth and morphogenesis are coordinated during animal development. A future challenge will be to more precisely characterize the growth component itself. Is growth continuous throughout, merely spatially redirected between phases? Or does its rate and regulation shift, possibly in feedback with the forces shaping the tissue?

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12. Amlan, B., Matis, S., Wang, X., Shao-Zhen, L., Marc, K., Elsa, B., Sylvie, R., Brice, L., Claire, C., Dominique, B., et al. (2025). A multicellular actin star network underpins epithelial organization and connectivity. Preprint at bioRxiv,
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Figure 1: Coupling of morphogenesis and growth during fly retina development

A) Scheme of a mature *Drosophila* ommatidia, illustrating its complex organization, and its elongated and conical shape. Each color illustrates a different cell type. B) Summary of the two phases on adult fly retina during metamorphosis. Retina can be simplified as a simple uniform epithelial sheet. A first phase corresponds to a planar expansion and a curvature increase, likely induced by internal hydrostatic pressure and permitted by a low cortical tension allowing deformation. The second phase is driven by a strong increase of basal tension that contracts the basal domains and orients growth that, in turn, induces cell elongation along apical-basal axis and thus tissue thickening.