Optogenetic control of developmental signaling pathways

How a complex multicellular organism forms from a single cell is a question that defies simplistic understanding. Yet, embryonic developmental programs use a surprisingly small set of signaling pathways to pattern the embryonic tissue into germ layers from which the various tissues and organs emerge. A hallmark of embryonic development is that these recurring developmental signaling pathways are carefully orchestrated in space and time to facilitate proper development. Understanding the spatiotemporal intricacies of these pathways necessitates tools which enable their perturbation in precisely defined spatiotemporal patterns. Optogenetics uses light-induced conformational changes to enable or disable protein-protein interactions, thereby permitting control of signal transduction at the flip of a switch. Consequently, light is emerging as a powerful tool to study embryonic development owing to its rapid, reversible and residue-free application, which empowers the researcher with excellent spatial and temporal control of signaling. Here, I first review recent accomplishments in optical microscopy and optogenetics which highlight the dual roles of light in visualizing as well as perturbing cellular microenvironments and processes. Second, I present an optogenetic approach to control the mitogen-activated protein kinase (MAPK) pathway which we successfully applied in both neuroblasts and frog embryos. Third, I demonstrate an optogenetic approach to control the Wnt signaling pathway in mammalian cells and frog embryos. Finally, I propose and provide working proof for a generalizable optogenetic platform to control those developmental signaling pathways, the activities of which involve the homo-association of plasma membrane-localized receptor tyrosine kinases.

Name thesis:degree_name

Ph.D.

Level thesis:degree_level

Dissertation

Discipline thesis:degree_discipline

Biochemistry

Grantor

University of Illinois at Urbana-Champaign

Year dc:date

2020

Author dc:creator

• Krishnamurthy, Vishnu Vardhan

Contributors dc:contributor

• Zhang, Kai
• Fratti, Rutilio A
• Ceman, Stephanie
• Kalsotra, Auinash

• Developmental signaling
• Optogenetics
• CRY2-CIBN
• Raf1
• LRP6
• Wnt
• FGFR
• TrkA
• TrkB
• RTK
• Xenopus

Statement dc:rights

• Copyright 2019 Vishnu Krishnamurthy

Language dc:language

en

Handle dc:identifier

http://hdl.handle.net/2142/106445

OAI identifier oai:identifier

oai:www.ideals.illinois.edu:2142/106445