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Multimodal transcriptional control of pattern formation in embryonic development

Lammers, Nicholas C. and Galstyan, Vahe and Reimer, Armando and Medin, Sean A. and Wiggins, Chris H. and Garcia, Hernan G. (2018) Multimodal transcriptional control of pattern formation in embryonic development. . (Unpublished)

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Predicting developmental outcomes from regulatory DNA sequence and transcription factor patterns remains an open challenge in physical biology. Using stripe 2 of the even-skipped gene in Drosophila embryos as a case study, we dissect the regulatory forces underpinning a key step along the developmental decision-making cascade: the generation of cytoplasmic mRNA patterns via the control of transcription in individual cells. Using live imaging and computational approaches, we found that the transcriptional burst frequency is modulated across the stripe to control the mRNA production rate. However, we discovered that bursting alone cannot quantitatively recapitulate the formation of the stripe, and that control of the window of time over which each nucleus transcribes even-skipped plays a critical role in stripe formation. Theoretical modeling revealed that these two regulatory strategies—bursting and the time window—obey different kinds of regulatory logic, suggesting that the stripe is shaped by the interplay of two distinct underlying molecular processes.

Item Type:Report or Paper (Discussion Paper)
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URLURL TypeDescription Paper
Lammers, Nicholas C.0000-0001-6832-6152
Galstyan, Vahe0000-0001-7073-9175
Additional Information:The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license. bioRxiv preprint first posted online May. 31, 2018. We thank Thomas Gregor and Lev Barinov for discussion about an initial implementation of the mHMM approach, Florian Jug for help with the spot segmentation using machine learning, and Elizabeth Eck, Maryam Kazemzadeh-Atou1 and Jonathan Liu for the P2 data used in the absolute MS2 calibration and for the Bicoid-GFP data used in the logistic regression. We are also grateful to Jack Bateman, Jane Kondev, Rob Phillips, Allyson Sgro, Donald Rio and Richard Harland for comments and discussion on the manuscript. HGG was supported by the Burroughs Wellcome Fund Career Award at the Scientific Interface, the Sloan Research Foundation, the Human Frontiers Science Program, the Searle Scholars Program, the Shurl & Kay Curci Foundation, the Hellman Foundation, the NIH Director’s New Innovator Award (DP2 OD024541-01), and an NSF CAREER Award (1652236). NL was supported by NIH Genomics and Computational Biology training grant 5T32HG000047-18. CW was supported by the NIH/NIC (U54 CA193313), CUNY (RFCUNY 40D14-A), and the NSF (IIS-1344668).
Funding AgencyGrant Number
Burroughs Wellcome FundUNSPECIFIED
Alfred P. Sloan FoundationUNSPECIFIED
Human Frontier Science ProgramUNSPECIFIED
Searle Scholars ProgramUNSPECIFIED
Shurl and Kay Curci FoundationUNSPECIFIED
Hellman FoundationUNSPECIFIED
NIHDP2 OD024541-01
NIH Predoctoral Fellowship5T32HG000047-18
NIHU54 CA193313
Columbia UniversityRFCUNY 40D14-A
Record Number:CaltechAUTHORS:20190412-102028041
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Official Citation:Multimodal transcriptional control of pattern formation in embryonic development. Nicholas C Lammers, Vahe Galstyan, Armando Reimer, Sean A Medin, Chris H Wiggins, Hernan G Garcia. bioRxiv 335919; doi:
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:94689
Deposited By: Tony Diaz
Deposited On:12 Apr 2019 22:24
Last Modified:12 Apr 2019 22:24

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