Abstracts - Society for Developmental Biology

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ureteric insertion into the bladder. Furthermore, mesenchyme-specific expression of GLI3R controls UB induction. Our
findings identify multiple and distinct lineage-specific roles for GLI3R in early urinary tract development.
Program/Abstract # 462
Stromal signals regulate differentiation of the kidney progenitor population.
Carroll, Thomas J., UT Southwestern Med Ctr Internal Medicine and Molecular Biology, Dallas, United States
Kidney development in mammals requires reciprocal interactions between the ureteric bud and the adjacent metanephric
mesenchyme. Signals from the mesenchyme promote branching morphogenesis of the bud epithelium, while reciprocal
signals from this bud epithelium are necessary for the survival and renewal of a progenitor population within the
mesenchyme. A signal(s) from the bud also induces a sub-population of the progenitors to undergo a mesenchymal-toepithelial
transition (MET) and differentiate into epithelia that will give rise to the kidney nephrons. We identified Wnt9b
as signal that is necessary for both progenitor renewal and differentiation. Here, we address the mechanism whereby the
same molecule induces two seemingly contradictory processes. We show that signals from overlying stromal fibroblasts
modify the progenitor cells’ response to Wnt9b, determining whether they will proliferate or differentiate. This stromal
signal is mediated, at least in part, by the atypical cadherin Fat4. Utilizing these two opposing signals, differentiation and
growth of nephron progenitors is balanced, assuring proper organ size and function.
Program/Abstract # 463
ß-catenin controls branching morphogenesis via the Gdnf Ret Signaling axis during kidney development
Sarin, Sanjay, Hamilton, Canada; Li, Aihua; Bridgewater, Darren (Hamilton, Canada)
During kidney development, branching morphogenesis gives rise to the collecting duct system through growth, elongation
and branching of the ureteric epithelium. The ureteric epithelial induces the metanephric mesenchyme (MM) to undergo
nephrogenesis, the formation of nephrons. A failure in these two embryonic processes leads to renal dysplasia, the major
cause of childhood renal failure. β-catenin is normally expressed in the MM and over-expressed in renal dysplasia
suggesting an important role in kidney development. We generated a mouse model with β-catenin deficiency exclusively in
the metanephric mesenchyme. Mutants demonstrated renal hypoplasia by E13.5 and reduced ureteric branching. In-situ
hybridization of E11.5 kidneys revealed a marked reduction in Gdnf expression, but no changes in Ret or Wnt11,
molecules required for ureteric branching. To support β-catenin controls branching morphogenesis via regulating Gdnf
expression we generated a model of β-catenin over-expression exclusively in the metanephric mesenchyme. Mutants
displayed severe renal dysplasia and the formation of 4-6 ectopic kidneys. Analysis revealed marked abnormalities in
ureteric budding and branching. In situ hybridization of E11.5 kidneys demonstrated increased Gdnf, Ret and Wnt11
expression. A ChIP assay revealed that β-catenin directly bound to a TCF consensus binding site in the Gdnf 5’
untranslated region. Molecular cloning of this 4.9kb fragment upstream of a luciferase gene revealed β-catenin regulates
gene transcription from this site. Taken together, these data establish that β-catenin has an essential role in the metanephric
messenchyme to guide ureteric budding and branching through the regulation of the Gdnf signaling axis.
Program/Abstract # 464
Integrin-linked kinase (ILK) controls ureteric bud (UB) gene expression via p38MAPK-dependent and -
independent mechanisms
Smeeton, Joanna M.; Rosenblum, Norman, SickKids Toronto, Canada
In mammals, the renal collecting system is derived via growth, branching, and remodeling of the UB, a process termed
renal branching morphogenesis (RBM). The intracellular signaling pathways that control RBM are largely undefined.
Previously, we demonstrated that ILK controls UB branching via p38MAPK in vitro and is required for RBM in vivo
(Leung-Hagestejn et al, Mol Cell Biol, 2005; Smeeton et al, Development, 2010). To identify genetic targets of Ilk that
regulate RBM, we used whole transcriptome analysis of E12.5 kidneys from mutant mice with Ilk-deficiency in the UB and
from controls. Microarray analysis identified 227 differentially expressed mRNA transcripts (p