TY - JOUR
T1 - Heterophilic cell–cell adhesion of atypical cadherins Fat and Dachsous regulate epithelial cell size dynamics during Drosophila thorax morphogenesis
AU - Kumar, Amit
AU - Rizvi, Mohd Suhail
AU - Athilingam, Thamarailingam
AU - Parihar, Saurabh Singh
AU - Sinha, Pradip
N1 - Publisher Copyright:
© 2020 Kumar, Rizvi, Athilingam, et al.
PY - 2020/3
Y1 - 2020/3
N2 - Spatiotemporal changes in epithelial cell sizes—or epithelial cell size dynamics (ECD)—during morphogenesis entail interplay between two opposing forces: cell contraction via actomyosin cytoskeleton and cell expansion via cell–cell adhesion. Cell–cell adhesion–based ECD, however, has not yet been clearly demonstrated. For instance, changing levels of homophilic E-cadherin-based cell–cell adhesion induce cell sorting, but not ECD. Here we show that cell-expansive forces of heterophilic cell–cell adhesion regulate ECD: higher cell–cell adhesion results in cell size enlargement. Thus, ECD during morphogenesis in the heminotal epithelia of Drosophila pupae leading to thorax closure corresponds with spatiotemporal gradients of two heterophilic atypical cadherins—Fat (Ft) and Dachsous (Ds)—and the levels of Ft–Ds heterodimers formed concomitantly. Our mathematical modeling and genetic tests validate this mechanism of dynamic heterophilic cell–cell adhesion–based regulation of ECD. Conservation of these atypical cadherins suggests a wider prevalence of heterophilic cell–cell adhesion–based ECD regulation during animal morphogenesis.
AB - Spatiotemporal changes in epithelial cell sizes—or epithelial cell size dynamics (ECD)—during morphogenesis entail interplay between two opposing forces: cell contraction via actomyosin cytoskeleton and cell expansion via cell–cell adhesion. Cell–cell adhesion–based ECD, however, has not yet been clearly demonstrated. For instance, changing levels of homophilic E-cadherin-based cell–cell adhesion induce cell sorting, but not ECD. Here we show that cell-expansive forces of heterophilic cell–cell adhesion regulate ECD: higher cell–cell adhesion results in cell size enlargement. Thus, ECD during morphogenesis in the heminotal epithelia of Drosophila pupae leading to thorax closure corresponds with spatiotemporal gradients of two heterophilic atypical cadherins—Fat (Ft) and Dachsous (Ds)—and the levels of Ft–Ds heterodimers formed concomitantly. Our mathematical modeling and genetic tests validate this mechanism of dynamic heterophilic cell–cell adhesion–based regulation of ECD. Conservation of these atypical cadherins suggests a wider prevalence of heterophilic cell–cell adhesion–based ECD regulation during animal morphogenesis.
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U2 - 10.1091/MBC.E19-08-0468
DO - 10.1091/MBC.E19-08-0468
M3 - Article
C2 - 31877063
AN - SCOPUS:85082143386
SN - 1059-1524
VL - 31
SP - 546
EP - 560
JO - Molecular biology of the cell
JF - Molecular biology of the cell
IS - 7
ER -