TY - JOUR
T1 - CYK-1/Formin activation in cortical RhoA signaling centers promotes organismal left-right symmetry breaking
AU - Middelkoop, Teije C.
AU - Garcia-Baucells, Julia
AU - Quintero-Cadena, Porfirio
AU - Pimpale, Lokesh G.
AU - Yazdi, Shahrzad
AU - Sternberg, Paul W.
AU - Gross, Peter
AU - Grill, Stephan W.
N1 - Publisher Copyright:
© 2021 National Academy of Sciences. All rights reserved.
PY - 2021/5/18
Y1 - 2021/5/18
N2 - Proper left-right symmetry breaking is essential for animal development, and in many cases, this process is actomyosin-dependent. In Caenorhabditis elegans embryos active torque generation in the actomyosin layer promotes left-right symmetry breaking by driving chiral counterrotating cortical flows. While both Formins and Myosins have been implicated in left-right symmetry breaking and both can rotate actin filaments in vitro, it remains unclear whether active torques in the actomyosin cortex are generated by Formins, Myosins, or both. We combined the strength of C. elegans genetics with quantitative imaging and thin film, chiral active fluid theory to show that, while Non-Muscle Myosin II activity drives cortical actomyosin flows, it is permissive for chiral counterrotation and dispensable for chiral symmetry breaking of cortical flows. Instead, we find that CYK-1/Formin activation in RhoA foci is instructive for chiral counterrotation and promotes in-plane, active torque generation in the actomyosin cortex. Notably, we observe that artificially generated large active RhoA patches undergo rotations with consistent handedness in a CYK-1/Formin-dependent manner. Altogether, we conclude that CYK-1/Formin-dependent active torque generation facilitates chiral symmetry breaking of actomyosin flows and drives organismal left-right symmetry breaking in the nematode worm.
AB - Proper left-right symmetry breaking is essential for animal development, and in many cases, this process is actomyosin-dependent. In Caenorhabditis elegans embryos active torque generation in the actomyosin layer promotes left-right symmetry breaking by driving chiral counterrotating cortical flows. While both Formins and Myosins have been implicated in left-right symmetry breaking and both can rotate actin filaments in vitro, it remains unclear whether active torques in the actomyosin cortex are generated by Formins, Myosins, or both. We combined the strength of C. elegans genetics with quantitative imaging and thin film, chiral active fluid theory to show that, while Non-Muscle Myosin II activity drives cortical actomyosin flows, it is permissive for chiral counterrotation and dispensable for chiral symmetry breaking of cortical flows. Instead, we find that CYK-1/Formin activation in RhoA foci is instructive for chiral counterrotation and promotes in-plane, active torque generation in the actomyosin cortex. Notably, we observe that artificially generated large active RhoA patches undergo rotations with consistent handedness in a CYK-1/Formin-dependent manner. Altogether, we conclude that CYK-1/Formin-dependent active torque generation facilitates chiral symmetry breaking of actomyosin flows and drives organismal left-right symmetry breaking in the nematode worm.
KW - left-right asymmetry
KW - |Formin
KW - RhoA signaling
KW - C
KW - elegans
KW - LEFT-RIGHT ASYMMETRY
KW - ACTIN-FILAMENT
KW - UNCONVENTIONAL MYOSIN
KW - FORMIN MDIA1
KW - C. ELEGANS
KW - F-ACTIN
KW - HANDEDNESS
KW - CHIRALITY
KW - POLARITY
KW - MOVEMENT
KW - C. elegans
KW - Left-right asymmetry
KW - Formin
UR - http://www.scopus.com/inward/record.url?scp=85105771641&partnerID=8YFLogxK
U2 - 10.1073/pnas.2021814118
DO - 10.1073/pnas.2021814118
M3 - Article
SN - 0027-8424
VL - 118
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 20
M1 - e2021814118
ER -