Seminars and Symposia
IDAC Seminar, 6 April 2016
|Secretariat, Alumni Association, IDAC|
|Date||Wednesday,6 April 2016, 17:00～|
|Room||Seminar-shitsu 1, IDAC Research building 7F|
|Title||γ-secretase and LARG mediate distinct RGMa activities to control appropriate layer targeting within the optic tectum|
|Affiliation||University of Toronto|
|Person-in-charge||Wataru Shoji（Department of Project Programs・ext.795-4734）|
|Abstract||RGMa plays a pivotal role for guiding retinal ganglion cell (RGC) axons along the antero-posterior axis of the chick optic tectum. However, it is still unclear the mechanisms how two distinctive forms of RGMa, N-RGMa and C-RGMa, transduce intracellular signaling using its receptor Neogenin and roles for these peptide in retinotectal pathfinding.
We performed in vivo and in vitro experiments in chick retinotectal system. C-RGMa utilized a LARG/Rho/Rock pathway to inhibit axonal growth. N-RGMa on the other hand relied on γ -secretase cleavage of the intracellular portion of Neogenin to generate an intracellular domain (NeICD) that used LMO4 to block growth. Next Overexpression of C-RGMa and dominant-negative LARG in vivo induced overshoots in the superficial tectal layer but not in deeper tectal layers at E18, indicating that C-RGMa may act as a barrier to descending axons. In contrast both N-RGMa and NeICD overexpression resulted in aberrant axonal-paths, all of which suggests that it is a repulsive guidance molecule.
These data reveal how retinal projections are targeted to the appropriate layer in their target tissue.