Combinatorial patterns of graded RhoA activation and uniform F-actin depletion promote tissue curvature
Name
2020.04.15.043893v1.full.pdf
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Submitted version
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Author(s) • • • •
Denk-Lobnig, Marlis
Totz, Jan F
Heer, Natalie C
Dunkel, Jörn
Martin, Adam C
Date Issued
2021
Journal
Development
Publisher
The Company of Biologists
Citation
Denk-Lobnig, Marlis, Totz, Jan F, Heer, Natalie C, Dunkel, Jörn and Martin, Adam C. 2021. "Combinatorial patterns of graded RhoA activation and uniform F-actin depletion promote tissue curvature." Development, 148 (11).
Version
Original manuscript
Abstract
ABSTRACT
During development, gene expression regulates cell mechanics and shape to sculpt tissues. Epithelial folding proceeds through distinct cell shape changes that occur simultaneously in different regions of a tissue. Here, using quantitative imaging in Drosophila melanogaster, we investigate how patterned cell shape changes promote tissue bending during early embryogenesis. We find that the transcription factors Twist and Snail combinatorially regulate a multicellular pattern of lateral F-actin density that differs from the previously described Myosin-2 gradient. This F-actin pattern correlates with whether cells apically constrict, stretch or maintain their shape. We show that the Myosin-2 gradient and F-actin depletion do not depend on force transmission, suggesting that transcriptional activity is required to create these patterns. The Myosin-2 gradient width results from a gradient in RhoA activation that is refined through the balance between RhoGEF2 and the RhoGAP C-GAP. Our experimental results and simulations of a 3D elastic shell model show that tuning gradient width regulates tissue curvature.
During development, gene expression regulates cell mechanics and shape to sculpt tissues. Epithelial folding proceeds through distinct cell shape changes that occur simultaneously in different regions of a tissue. Here, using quantitative imaging in Drosophila melanogaster, we investigate how patterned cell shape changes promote tissue bending during early embryogenesis. We find that the transcription factors Twist and Snail combinatorially regulate a multicellular pattern of lateral F-actin density that differs from the previously described Myosin-2 gradient. This F-actin pattern correlates with whether cells apically constrict, stretch or maintain their shape. We show that the Myosin-2 gradient and F-actin depletion do not depend on force transmission, suggesting that transcriptional activity is required to create these patterns. The Myosin-2 gradient width results from a gradient in RhoA activation that is refined through the balance between RhoGEF2 and the RhoGAP C-GAP. Our experimental results and simulations of a 3D elastic shell model show that tuning gradient width regulates tissue curvature.
MIT Department
Massachusetts Institute of Technology. Department of Mathematics
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DOI of Published Version
https://doi.org/10.1242/DEV.199232