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Optogenetic Control of the BMP Signaling Pathway.


ABSTRACT: Bone morphogenetic proteins (BMPs) are members of the transforming growth factor ? (TGF?) superfamily and have crucial roles during development; including mesodermal patterning and specification of renal, hepatic, and skeletal tissues. In vitro developmental models currently rely upon costly and unreliable recombinant BMP proteins that do not enable dynamic or precise activation of the BMP signaling pathway. Here, we report the development of an optogenetic BMP signaling system (optoBMP) that enables rapid induction of the canonical BMP signaling pathway driven by illumination with blue light. We demonstrate the utility of the optoBMP system in multiple human cell lines to initiate signal transduction through phosphorylation and nuclear translocation of SMAD1/5, leading to upregulation of BMP target genes including Inhibitors of DNA binding ID2 and ID4. Furthermore, we demonstrate how the optoBMP system can be used to fine-tune activation of the BMP signaling pathway through variable light stimulation. Optogenetic control of BMP signaling will enable dynamic and high-throughput intervention across a variety of applications in cellular and developmental systems.

SUBMITTER: Humphreys PA 

PROVIDER: S-EPMC7927147 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature

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Optogenetic Control of the BMP Signaling Pathway.

Humphreys Paul A PA   Woods Steven S   Smith Christopher A CA   Bates Nicola N   Cain Stuart A SA   Lucas Robert R   Kimber Susan J SJ  

ACS synthetic biology 20201021 11


Bone morphogenetic proteins (BMPs) are members of the transforming growth factor β (TGFβ) superfamily and have crucial roles during development; including mesodermal patterning and specification of renal, hepatic, and skeletal tissues. <i>In vitro</i> developmental models currently rely upon costly and unreliable recombinant BMP proteins that do not enable dynamic or precise activation of the BMP signaling pathway. Here, we report the development of an optogenetic BMP signaling system (optoBMP)  ...[more]

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