Eph regulates dorsoventral asymmetry of the notochord plate and convergent extension-mediated notochord formation.
BACKGROUND
The notochord is a signaling center required for the patterning of the vertebrate embryonic midline, however, the molecular and cellular mechanisms involved in the formation of this essential embryonic tissue remain unclear. The urochordate Ciona intestinalis develops a simple notochord from 40 specific postmitotic mesodermal cells. The precursors intercalate mediolaterally and establish a single array of disk-shaped notochord cells along the midline. However, the role that notochord precursor polarization, particularly along the dorsoventral axis, plays in this morphogenetic process remains poorly understood.


RESULTS
Here we show that the notochord preferentially accumulates an apical cell polarity marker, aPKC, ventrally and a basement membrane marker, laminin, dorsally. This asymmetric accumulation of apicobasal cell polarity markers along the embryonic dorsoventral axis was sustained in notochord precursors during convergence and extension. Further, of several members of the Eph gene family implicated in cellular and tissue morphogenesis, only Ci-Eph4 was predominantly expressed in the notochord throughout cell intercalation. Introduction of a dominant-negative Ci-Eph4 to notochord precursors diminished asymmetric accumulation of apicobasal cell polarity markers, leading to defective intercalation. In contrast, misexpression of a dominant-negative mutant of a planar cell polarity gene Dishevelled preserved asymmetric accumulation of aPKC and laminin in notochord precursors, although their intercalation was incomplete.


CONCLUSIONS
Our data support a model in which in ascidian embryos Eph-dependent dorsoventral polarity of notochord precursors plays a crucial role in mediolateral cell intercalation and is required for proper notochord morphogenesis.
Cardiovascular Research Institute, University of California San Francisco, San Francisco, California, United States of America.
Izumi
I
Oda-Ishii
Yasuo
Y
Ishii
Takashi
T
Mikawa
D000818:Animals; D019521:Body Patterning / Q000502:physiology*; D002938:Ciona intestinalis / Q000196:embryology*; D009672:Notochord / Q000196:embryology*; D036081:Receptors, Eph Family / Q000235:genetics*
D036081:Receptors, Eph Family