Die biologische Rolle und der Wirkungsmechanismus von R-sponding2
Final Report Abstract
Rspo3 constitutive knock out mice and Rspo3 Morphants in Xenopus show defects in the craniofacial region. Detailed analysis notably in Xenopus revealed that this defect is due to a novel role of Rspo3 in non-canonical Wnt signalling. Nevertheless, mice mutants also show a definitive defect in dorsal root ganglia, which is likely a direct effect of Rspo3 on NC. Yet, constitutive knockout cannot be efficiently used for this analysis, as these embryos die at E10 because of placental defects. Unfortunately, the normal development of Rspo3 conditional Nestin-Cre mutant mice makes this mouse model unsuitable for study of Rspo3 function in the embryonic brain. Similarly in Xenopus, our results do not exclude a possibility of a role in NC, but they indicate that Rspo3 has multiple functions in head development, notably on mesoderm. Because CNS development is closely affected by the surrounding tissues, this complicates the analysis of neural tissues at each stage in Xenopus. Thus for similar reasons in both frog and mouse, we rather focussed on the role of Rspo3 in mesoderm development, where we discovered a novel function of the gene in Wnt PCP signalling and its role in two developmental processes, gastrulation and head cartilage development. This led to a study on its own. In passing, this work also generated the first useful Wnt/PCP luciferase reporter.
Publications
- (2008) The Wnt signaling regulator R-spondin3 acts upstream of VEGF to control the switch between angioblastic and hematopoietic cell fate determination. Development 135:3655-3664
Kazanskaya, O., Ohkawara, B., Heroult, M., Maltry, N., Augustin, H.G., and Niehrs, C.
- (2010). An ATF2-based luciferase reporter to monitor noncanonical Wnt signaling in xenopus embryos. Dev Dyn. 240,188-194
Ohkawara B. and Niehrs C.
