My research focuses on the molecular mechanisms of growth cone turning in guidance. Growth cones have an amazing ability to detect and migrate toward extremely shallow gradients of long distance guidance cues such as netrin-1 and neurotrophin 3. These gradients can be as small as 1-2% differences in concentration (or receptor occupancy) on the leading edge versus the trailing edges of these growth cones. Therefore, the growth cone must rely on an inherent amplification mechanisms to overcome this signal to noise problem. By analogy to what is observed in Dictyostelium discoideum and neutrophils, amplification of a shallow gradient may occur by localized amplification of a receptor mediated signal (through feed forward stimulation of signaling tranduction cascades and localised recruitment of signaling factors such as akt and PIP3) and a back propagating inhibition of all other signals (possibly PTEN and global depletion of substrate by the localised amplification).
Little is known about either the initial steps of amplification or the back propagating inhibitory signal. What we do know is that based on previous work published from our lab cAMP, Ca2+ and PI3K are intimately involved with this response. Downstream of these signals are the rhoGTPases, namely rac and cdc42, which are known to be dynamic regulators of the actin cytoskeleton. Using a combination of molecular biology and real time confocal microscopy, it is my aim to define the molecular events underlying signal amplification and determine if an understanding of these events can shed light on why some guidance cues are attractive (netrin-1, BDNF and NT3) whereas others are repulsive (Semaphorin III, rMAG and EphB ligand).
Scott Wong
Poo Laboratory /
221 LSA
University of California, Berkeley
Department of Molecular and Cell Biology
142 Life Sciences Addition # 3200
Berkeley CA 94720-3200 USA
stwong@uclink.berkeley.edu
mcb.berkeley.edu/labs/poo/people/wong/
510 643 4576 tel
510 642 2544 fax