Abstracts - Society for Developmental Biology

158
Eph receptors.
Rohani Larijani, Nazanin, McGill University, Montreal, Canada; Winklbauer, Rudolf (Toronto, Canada); Fagotto,
Francois (Montreal, Canada)
The physical segregation of embryonic tissues is a fundamental process in the development of multicellular organisms. Its
perturbation leads to severe developmental defects, especially during phases of extensive cell movements, such as
gastrulation. In vertebrate embryos, this process often depends on ephrins and Eph receptors. We have previously shown
that ephrin/Eph-mediated repulsive signals generate cycles of adhesion and de-adhesion at the ectoderm/ mesoderm
boundary. This mechanism explains how the two tissues can maintain intimate contacts with each other without mixing.
The system is astonishingly complex, with both ectoderm and mesoderm expressing a variety of ephrins and Ephs, which
could in principle signal and induce repulsion between cells within each tissue. Co-expression of ephrins and Ephs within
the same cells has been also observed in the neural tissues, but how signaling is integrated under such conditions has
remained largely unresolved. We present here a simple explanation for the strict confinement of repulsion to the ectodermmesoderm
interface. We identify selective functional interactions between pairs of ephrins and Ephs, and we show that the
asymmetric expression of these pairs is sufficient to account for selective cell detachments across the boundary. Ephrin-
Eph signals also occur within the tissues, but their intensity is below the threshold required to disrupt adhesive bonds.
These results provide a paradigm for how developmental systems may integrate multiple cues to control precisely
morphogenetic processes, which may be applicable to other complex situations such as brain development.
Program/Abstract # 477
The role of Wnt9b-signaling in kidney development
Kitzler, Thomas; Iglesias, Diana; Corsini, Rachel; Saban, Jeremy; Zhang, Zhao; Goodyer, Paul, McGill University,
Montreal, Canada
Acute kidney injury is a frequent clinical complication with high mortality. Recently it has been shown that the adult
kidney retains some of the original progenitor cells. To understand how these cells may participate in the repair of nephron
damage, it is crucial to understand how progenitor cells develop into nephrons during embryonic life. As the ureteric bud
penetrates the column of mesenchymal progenitor cells, each branch tip secretes a soluble protein, WNT9b, a canonical
WNT signaling molecule, which induces nearby mesenchymal progenitor cells to cluster into a tight “cap” of cells that
differentiate into a single nephron. Only the immediate layer of renal progenitor cells responds to the WNT9b signal. This
implies that the ureteric bud may control responsiveness to its WNT9b signal. We hypothesize that this is accomplished by
release of microvesicles (MV) from the ureteric bud, carrying both, receptor and ligand. Frizzled (FRZ) proteins comprise
a family of G protein-coupled receptors that transduce WNT signals. We discovered that renal progenitor cells from
embryonic mice are responsive to WNT9b signals from co-cultured embryonic mouse ureteric bud cells, but not to cocultured
mouse fibroblasts that express WNT9b in the absence of FRZ4 and FRZ8, two main putative candidates. By RT-
PCR we found that HEK293 cells did neither express FRZ4 nor FRZ8. Co-transfection of these cells with canonical WNTreporter
and co-culture with LWNT9b cells, that have been co-transfected with FRZ4 or FRZ8, lead to an increase in
reporter activity. By immunoblotting we could demonstrate FRZs in the MV fraction of the transfected cells. This suggests
that co-transfer of Wnt9b and FRZ receptors is required for canonical WNT signaling.