| RRC ID |
74675
|
| 著者 |
Osswald M, Barros-Carvalho A, Carmo AM, Loyer N, Gracio PC, Sunkel CE, Homem CCF, Januschke J, Morais-de-Sá E.
|
| タイトル |
aPKC regulates apical constriction to prevent tissue rupture in the Drosophila follicular epithelium.
|
| ジャーナル |
Curr Biol
|
| Abstract |
Apical-basal polarity is an essential epithelial trait controlled by the evolutionarily conserved PAR-aPKC polarity network. Dysregulation of polarity proteins disrupts tissue organization during development and in disease, but the underlying mechanisms are unclear due to the broad implications of polarity loss. Here, we uncover how Drosophila aPKC maintains epithelial architecture by directly observing tissue disorganization after fast optogenetic inactivation in living adult flies and ovaries cultured ex vivo. We show that fast aPKC perturbation in the proliferative follicular epithelium produces large epithelial gaps that result from increased apical constriction, rather than loss of apical-basal polarity. Accordingly, we can modulate the incidence of epithelial gaps by increasing and decreasing actomyosin-driven contractility. We traced the origin of these large epithelial gaps to tissue rupture next to dividing cells. Live imaging shows that aPKC perturbation induces apical constriction in non-mitotic cells within minutes, producing pulling forces that ultimately detach dividing and neighboring cells. We further demonstrate that epithelial rupture requires a global increase of apical constriction, as it is prevented by the presence of non-constricting cells. Conversely, a global induction of apical tension through light-induced recruitment of RhoGEF2 to the apical side is sufficient to produce tissue rupture. Hence, our work reveals that the roles of aPKC in polarity and actomyosin regulation are separable and provides the first in vivo evidence that excessive tissue stress can break the epithelial barrier during proliferation.
|
| 巻・号 |
32(20)
|
| ページ |
4411-4427.e8
|
| 公開日 |
2022-10-24
|
| DOI |
10.1016/j.cub.2022.08.063
|
| PII |
S0960-9822(22)01385-9
|
| PMID |
36113470
|
| PMC |
PMC9632327
|
| MeSH |
Actomyosin / metabolism
Animals
Cell Polarity / physiology
Constriction
Drosophila* / metabolism
Drosophila Proteins* / metabolism
Drosophila melanogaster / metabolism
Epithelial Cells / metabolism
Epithelium / metabolism
Protein Kinase C / genetics
Protein Kinase C / metabolism
|
| IF |
9.601
|
| リソース情報 |
| ショウジョウバエ |
DGRC#115082
DGRC#104055 |
