Heterophilic cell–cell adhesion of atypical cadherins Fat and Dachsous regulate epithelial cell size dynamics duringDrosophilathorax morphogenesis

Abstract

Epithelial morphogenesis is marked by dynamic changes in cell sizes until the final adult organ is formed. Using a combination of quantitative, mathematical simulation and genetic techniques, this paper reveals a novel mechanism of epithelial cell size regulation based on heterophilic cell–cell adhesion between two atypical cadherins, Ft and Ds.

Evolution of mechanisms controlling epithelial morphogenesis across animals: new insights from dissociation - reaggregation experiments in the sponge Oscarella lobularis.

“…In vertebrates, C-type lectin domain proteins are known to facilitate the Ca 2+ -dependent cell-matrix and cell-cell interactions (Rodriguez-Teja et al, 2015). In the same way, Fat 4 and Cadherin 23 proteins were shown to regulate cell-cell adhesion and to be involved in dynamic changes leading to epithelial fluid-like attributes in bilaterians (Apostolopoulou and Ligon, 2012; Kumar et al, 2019).…”

DegeneratingDrosophilaLarval Epidermal Cells Drive Thorax Closure

“…In Drosophila, thorax closure sets in at an early stage of pupal development-often referred to as 'pre-pupal' stage (0-12 hrs after puparium formation (APF) (Fristrom and Fristrom, 1993))-that lasts from 4.30 to 6.00 hrs APF at 25 C (Kumar et al, 2020;Martín-Blanco et al, 2000;Usui and Simpson, 2000;Zeitlinger and Bohmann, 1999). Leading-edge (LE) cells of the contralateral HEs-which are seen in close apposition with the underlying LEC layer (Martín-Blanco et al, 2000;Pastor-Pareja et al, 2004;Usui and Simpson, 2000)-display upregulated expression of a JNK reporter, puc-lacZ ( Figure 1A, A'), besides actin-enriched filopodial and lamellipodial protrusions (red and blue arrows, respectively, Figure 1A').…”

“…0 hrs APF pupae were carefully selected and dissected at desired time points, as described previously (Kumar et al, 2020). In brief, dissection was performed and fixed in 4% PF in 1X…”

“…Thorax closure ensues (Fristrom and Fristrom, 1993) when these two opposing contralateral HEs migrate, replacing the LEC layer and zip at the future midline of the adult body: a culmination of an elegant process of epithelial tissue closure (see Figure S1A) (Agnès et al, 1999;Kumar et al, 2020;Martín-Blanco et al, 2000;Usui and Simpson, 2000;Zeitlinger and Bohmann, 1999).…”

“…vertex models have been utilized extensively to study epithelial mechanics in several developmental contexts, such as oriented cell divisions(Mao et al, 2011), density-independent phase transitions(Bi et al, 2015), epithelial topology(Aegerter-Wilmsen et al, 2010), cell flows during epithelial morphogenesis(Aigouy et al, 2010), cell size oscillations(Lin et al, 2017) or cell-cell adhesion mediated cell size dynamics(Kumar et al, 2020). In our vertex model, the mechanical response of the cells (LECs as well as HEs) is characterized by an energy function (Figure 5A) comprising of contributions from cell elasticity arising due to impermeability, or absence of leakiness of cell membrane, actomyosin-driven cell contractility and cadherin or integrin (at the interface of LEC layer and HE) mediated cell-cell adhesion(Farhadifar et al, 2007;Kumar et al, 2020). For overdamped cellular dynamics, the velocities of vertices are taken as proportional to the forces which are calculated from derivative of the energy functional relative to the vertex positions (Figure 5A, see Materials and methods).The numerical simulation of the vertex model of LEC and HE recapitulates the experimental observations, as shown (first panel in Video 7,Figure 5B).…”