The mechanisms of how growth cones integrate simultaneous guidance instructions or how they modify responsiveness to sequential cues along their trajectories have not been well understood. Our preliminary study revealed a novel gene-expression-based switch mechanism. Our previous work showed that planar cell polarity (PCP) signaling is essential for their proper anterior-posterior (A-P) guidance after midline crossing. We now found that Sonic Hedgehog (Shh) induces a subset of PCP genes in commissural neurons during midline crossing. We propose that this novel regulatory loop between Shh and PCP signaling may also be essential in many other cases of axon guidance or in developmental processes other than axon guidance. In this exploratory R21 grant, we propose to understand the mechanisms of how Shh-Smo signaling activates the PCP gene expression.

Public Health Relevance

The mechanisms of how growth cones integrate simultaneous guidance instructions or how they modify responsiveness to sequential cues along their trajectories have not been well understood. In this exploratory R21 grant, we propose to understand the mechanisms of how Shh-Smo signaling activates gene expression in regulating axon responsiveness.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Exploratory/Developmental Grants (R21)
Project #
5R21NS095615-02
Application #
9215701
Study Section
Special Emphasis Panel (ZRG1-MDCN-T (02)M)
Program Officer
Riddle, Robert D
Project Start
2016-03-01
Project End
2018-02-28
Budget Start
2017-03-01
Budget End
2018-02-28
Support Year
2
Fiscal Year
2017
Total Cost
$174,375
Indirect Cost
$61,875
Name
University of California San Diego
Department
Biology
Type
Schools of Arts and Sciences
DUNS #
804355790
City
La Jolla
State
CA
Country
United States
Zip Code
92093