Abstracts - Society for Developmental Biology

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limbs. Apoptosis was also perturbed, leading to abnormal overgrowth of the developing autopod as well as ectopic soft
tissue outgrowths. SOX9 was not detected at sites of presumptive digit formation in the anterior limb, instead markers for
the interdigital mesenchyme Msx1 and Msx2 were ectopically expressed. The expression of markers for the anterior limb
however were not affected. These data suggest that the absence of anterior and distal skeletal elements in Chrdl1-
overexpressing limbs is likely due to inhibition of chondrogenic differentiation rather than a defect in patterning the
anterior limb.
Program/Abstract # 408
Hedgehog signaling acts upstream of Foxd1 to control the renal capsule
Martirosyan, John; Rosenblum, Norman (Toronto, Canada)
The renal capsule is a flattened layer of cells which invest the kidney and give rise to stromal cells in the kidney cortex.
Differentiation of capsule cells is known to be dependent on the transcription factor Foxd1. While expression of Indian
Hedgehog (IHH) and Gli1 in murine embryonic capsule cells suggest HH activity, HH functions in this domain are
undefined. We hypothesize that HH activity controls capsule morphogenesis in the embryonic kidney. Mice with loss of
HH signalling in capsule cells were generated by interbreeding Foxd1-Cre and Smoothened-loxP (Smo loxP/loxP) mice.
Compound mutant mice were characterized by decreased expression of Gli1 and Ptch1, markers of HH activity, in capsule
cells. Analysis of newborn mutant mouse kidney using histology and scanning electron microscopy demonstrated regions
on the surface of the kidney where no capsule cells were present. Furthermore, the outer cortex underlying these regions
was interrupted by tubules and mature glomeruli, which normally exist in the inner cortex. The discontinuous capsule
phenotype was observed only after E13.5 by which stage capsule cells lost expression of the markers Foxd1 and Raldh2
and demonstrated decreased proliferation by 54%. Mice with a severe loss of renal capsule died immediately after birth
while less severely affected mice survived to adulthood with normal kidney function. These results indicate that HH
signalling acts upstream of Foxd1 to control capsule cell differentiation and proliferation.
Program/Abstract # 409
Stromally expressed ß-catenin regulates branching morphogenesis and nephrogenesis during kidney development
Boivin, Felix, McMaster University, Dundas, Canada; Bridgewater, Darren (Hamilton, Canada)
Formation of the mammalian kidney is dependent upon branching morphogenesis, defined as growth and branching of the
ureteric epithelium, and nephrogenesis, the formation of nephrons from the kidney mesenchyme. Deletion of ß-catenin
from the ureteric epithelial cells or kidney mesenchyme results in severe renal dysplasia, suggesting an essential role for ß-
catenin in kidney development. We recently demonstrated ß-catenin localizes to the nuclear compartment of the renal
stroma in embryonic and mature kidneys suggesting a functional role in kidney development. We hypothesize that
stromally expressed ß-catenin plays an essential role in regulating branching morphogenesis and nephrogenesis. To support
our hypothesis we generated a mouse model whereby ß-catenin is deleted in the renal stroma. Gross anatomical and
histological analysis revealed renal hypodysplasia, pancake-like kidneys, a lack of renal capsule, ill-defined nephrogenic
zone, and reduced condensed mesenchyme. The analysis of ureteric branch patterning revealed elongated and disorganized
epithelial branches by E12.5. To provide support for a molecular mechanism we generated a mouse model that
overexpresses ß-catenin exclusively in the renal stroma. Gross anatomical and histological analysis demonstrated bilateral
renal aplasia or severe hypodysplasia, markedly increased condensed mesenchyme, absence of nephrogenic structures, and
increased renal stroma. Analysis of branch pattern revealed disorganized and reduced epithelial branching. Taken together,
these studies indicate that ß-catenin plays an essential role in the formation of the renal stroma and in the regulation of
ureteric branching and nephrogenesis.
Program/Abstract # 410
Elucidation of the role of Rasip1 and Arhgap29 in blood vessel lumen formation
Koo, Yeon, , Dallas, United States; Xu, Ke; Fu, Stephen; Chong, Diana; Skaug, Brian; Chen, Zhijian (Dallas, United
States); Davis, George (Columbia, United States); Cleaver, Ondine (Dallas, United States)
Cardiovascular function depends on patent blood vessel formation by endothelial cells (ECs). Blood vessel development
initiates via the aggregation of ECs into tubes with a central lumen that allows blood flow. However the mechanisms
underlying vascular ‘tubulogenesis’ are only beginning to be unraveled. A recent study by our lab has demonstrated the
requirement for a novel GTPase-interacting protein called Rasip1, and its binding partner the RhoGAP, Arhgap29, for
blood vessel lumen formation. Rasip1 null mice showed disrupted localization of polarity and junctional complexes, and
loss of adhesion to extracellular matrix (ECM), resulting in failure of functional blood vessel formation. Depletion of
either Rasip1 and Arhgap29 in cultured endothelial cells caused increased RhoA/Rock/Myosin II activity, suggesting that
Rasip1 and Arhgap29 may function together to suppress RhoA mediated internal contractility. In vitro studies also