第1115回生物科学セミナー
Ipsi-laterality in Bi-laterality
Takashi Mikawa, Ph.D.（Science and Medicine University of California）
2016年10月05日(水) 14:55-16:40 理学部2号館 講堂
The majority of phyla have a bilateral symmetry of body plan organization. The bilateral symmetry
is one of the first patterning events in embryogenesis. During gastrulation and throughout life,
embryonic cells are permanently constrained to the original side, either the left or the right, without
crossing the midline. This ‘ipsilateral’ cell sorting is conserved amongst species; and yet, the
underlying mechanism of this fundamental morphogenetic program remains largely unexplained,
particularly in the amniote. Here we show that the primitive streak (PS), the signaling center and
conduit of amniote gastrulation, displays an array of active Caspase-3 (Cas-3) and apoptotic cell
death markers along the PS midline. Surprisingly, inhibition of Cas-3 action, either with molecular or
pharmacological antagonists, converted gastrulation, from ipsilateral to contralateral, allowing
epiblast cells to cross the midline into the contralateral side, both cell autonomously and
non-autonomously. These results lead to the model wherein the ipsilateral cell sorting in the
amniote is regulated by an active process, in part by Cas-3 activation-mediated programmed cell
death along the midline. Our data also suggest that the Cas-3 dependent cell death is a component
of a physical or cell biological barrier that prevents gastrulating cells from crossing the PS midline or
from invasion to the contralateral side of the amniote embryo. (Supported in part by NIH HL122375
and HHMI Gilliam Fellowship).
