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
Kornberg, Thomas B (2014) Cytonemes and the dispersion of morphogens. Wiley Interdiscip Rev Dev Biol 3:445-63
Kornberg, Thomas B; Roy, Sougata (2014) Communicating by touch--neurons are not alone. Trends Cell Biol 24:370-6
Roy, Sougata; Huang, Hai; Liu, Songmei et al. (2014) Cytoneme-mediated contact-dependent transport of the Drosophila decapentaplegic signaling protein. Science 343:1244624
Guerrero, Isabel; Kornberg, Thomas B (2014) Hedgehog and its circuitous journey from producing to target cells. Semin Cell Dev Biol 33:52-62
Kornberg, Thomas B (2014) The contrasting roles of primary cilia and cytonemes in Hh signaling. Dev Biol 394:1-5
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
Ibrahim, Daniel M; Biehs, Brian; Kornberg, Thomas B et al. (2013) Microarray comparison of anterior and posterior Drosophila wing imaginal disc cells identifies novel wing genes. G3 (Bethesda) 3:1353-62
Roy, Sougata; Hsiung, Frank; Kornberg, Thomas B (2011) Specificity of Drosophila cytonemes for distinct signaling pathways. Science 332:354-8
Guha, Arjun; Lin, Li; Kornberg, Thomas B (2009) Regulation of Drosophila matrix metalloprotease Mmp2 is essential for wing imaginal disc:trachea association and air sac tubulogenesis. Dev Biol :
Kornberg, Thomas B; Guha, Arjun (2007) Understanding morphogen gradients: a problem of dispersion and containment. Curr Opin Genet Dev 17:264-71

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