Our discovery of cytonemes, specialized filopodia that orient toward cells that express signaling proteins, suggest a novel mechanism to move signaling proteins between producing and target cells. This model postulates that signaling proteins move between cells in a manner similar to the way neurotransmitters move at neuronal synapses, that fundamentally, neurons and non-neuronal cells communicate in similar ways. Recent work from my lab now provides direct and convincing experimental evidence that cytonemes ferry signaling proteins between producing and receiving cells, strongly supporting the cytoneme model. Our work also identified several unexpected properties of cytonemes that have significant implications for mechanisms of signal transduction. The work proposed in this application will develop new tools for imaging cytonemes and will build upon our previous findings to determine the roles, composition and functions of these remarkable organelles.

Public Health Relevance

When cells in a developing animal grow to form tissues and organs, they often do so in response to gradients of chemical signals, yet the precise mechanisms by which these molecular messages move and are received is not known. Our work has provided strong evidence that thin finger-like protrusions from cells known as cytonemes play a key role in this process. Research proposed in this application will explore the structure and function of cytonemes and will have important implications for cell-cell signaling in all animals and in many contexts.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM030637-30
Application #
8600684
Study Section
Development - 1 Study Section (DEV1)
Program Officer
Hoodbhoy, Tanya
Project Start
1982-03-01
Project End
2015-12-31
Budget Start
2014-01-01
Budget End
2014-12-31
Support Year
30
Fiscal Year
2014
Total Cost
$372,651
Indirect Cost
$126,314
Name
University of California San Francisco
Department
Biochemistry
Type
Schools of Medicine
DUNS #
094878337
City
San Francisco
State
CA
Country
United States
Zip Code
94143
Chen, Weitao; Huang, Hai; Hatori, Ryo et al. (2017) Essential basal cytonemes take up Hedgehog in the Drosophila wing imaginal disc. Development 144:3134-3144
Kornberg, Thomas B (2017) Distributing signaling proteins in space and time: the province of cytonemes. Curr Opin Genet Dev 45:22-27
Kornberg, Thomas B (2017) Scripting a place in time. Dev Biol :
Huang, Hai; Kornberg, Thomas B (2016) Cells must express components of the planar cell polarity system and extracellular matrix to support cytonemes. Elife 5:
Roy, Sougata; Kornberg, Thomas B (2015) Paracrine signaling mediated at cell-cell contacts. Bioessays 37:25-33
Yu, Dan; Baird, Michelle A; Allen, John R et al. (2015) A naturally monomeric infrared fluorescent protein for protein labeling in vivo. Nat Methods 12:763-5
Huang, Hai; Kornberg, Thomas B (2015) Myoblast cytonemes mediate Wg signaling from the wing imaginal disc and Delta-Notch signaling to the air sac primordium. Elife 4:e06114
Rao, Prashanth R; Lin, Li; Huang, Hai et al. (2015) Developmental compartments in the larval trachea of Drosophila. Elife 4:
Kornberg, Thomas B; Roy, Sougata (2014) Communicating by touch--neurons are not alone. Trends Cell Biol 24:370-6
Yu, Dan; Gustafson, William Clay; Han, Chun et al. (2014) An improved monomeric infrared fluorescent protein for neuronal and tumour brain imaging. Nat Commun 5:3626

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