Institute of Development, Aging and Cancer, Tohoku University

Research

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
Speaker Hidekiyo Harada
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.