TY - JOUR
T1 - Temporal integration of inductive cues on the way to gastrulation
AU - McFann, Sarah
AU - Dutta, Sayantan
AU - Toettcher, Jared E.
AU - Shvartsman, Stanislav Y.
N1 - Funding Information:
figures, and the Flatiron Institute and the Lewis Sigler Institute for providing computing resources. This work was supported by the Hertz Fellowship and the NSF Graduate Research Fellowship Program (S.M.), NSF Faculty Early Career Development (CAREER) Award 1750663 (J.E.T.), and NIH Grant GM141843 (S.Y.S.).
Funding Information:
We thank the members of the Toettcher group, the Shvartsman group, J. Raimundo, E. Wieschaus, T. Sch?pbach, M. Levine, and B. Shilo for helpful conversations and suggestions. We thank G. Laevsky from the Princeton Nikon Imaging Facility for assistance with microscopy, A. Finkelstein for advice on tessellating curved surfaces, L. Reading-Ikkanda for designing figures, and the Flatiron Institute and the Lewis Sigler Institute for providing computing resources. This work was supported by the Hertz Fellowship and the NSF Graduate Research Fellowship Program (S.M.), NSF Faculty Early Career Development (CAREER) Award 1750663 (J.E.T.), and NIH Grant GM141843 (S.Y.S.).
Publisher Copyright:
© 2021 National Academy of Sciences. All rights reserved.
PY - 2021/6/8
Y1 - 2021/6/8
N2 - Markers for the endoderm and mesoderm germ layers are commonly expressed together in the early embryo, potentially reflecting cells' ability to explore potential fates before fully committing. It remains unclear when commitment to a single-germ layer is reached and how it is impacted by external signals. Here, we address this important question in Drosophila, a convenient model system in which mesodermal and endodermal fates are associated with distinct cellular movements during gastrulation. Systematically applying endoderm-inducing extracellular signal-regulated kinase (ERK) signals to the ventral medial embryo-which normally only receives a mesoderm-inducing cue-reveals a critical time window during which mesodermal cell movements and gene expression are suppressed by proendoderm signaling. We identify the ERK target gene huckebein (hkb) as the main cause of the ventral furrow suppression and use computational modeling to show that Hkb repression of the mesoderm-associated gene snail is sufficient to account for a broad range of transcriptional and morphogenetic effects. Our approach, pairing precise signaling perturbations with observation of transcriptional dynamics and cell movements, provides a general framework for dissecting the complexities of combinatorial tissue patterning.
AB - Markers for the endoderm and mesoderm germ layers are commonly expressed together in the early embryo, potentially reflecting cells' ability to explore potential fates before fully committing. It remains unclear when commitment to a single-germ layer is reached and how it is impacted by external signals. Here, we address this important question in Drosophila, a convenient model system in which mesodermal and endodermal fates are associated with distinct cellular movements during gastrulation. Systematically applying endoderm-inducing extracellular signal-regulated kinase (ERK) signals to the ventral medial embryo-which normally only receives a mesoderm-inducing cue-reveals a critical time window during which mesodermal cell movements and gene expression are suppressed by proendoderm signaling. We identify the ERK target gene huckebein (hkb) as the main cause of the ventral furrow suppression and use computational modeling to show that Hkb repression of the mesoderm-associated gene snail is sufficient to account for a broad range of transcriptional and morphogenetic effects. Our approach, pairing precise signaling perturbations with observation of transcriptional dynamics and cell movements, provides a general framework for dissecting the complexities of combinatorial tissue patterning.
KW - Developmental signaling
KW - Germ layer specification
KW - Morphogenesis
KW - Optogenetics
KW - Transcriptional dynamics
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U2 - 10.1073/pnas.2102691118
DO - 10.1073/pnas.2102691118
M3 - Article
C2 - 34083443
AN - SCOPUS:85107381083
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 - 23
M1 - e2102691118
ER -