Conditional Expression of Wnt4 during Chondrogenesis Leads to Dwarfism in Mice

Wnts are expressed in the forming long bones, suggesting roles in skeletogenesis. To examine the action of Wnts in skeleton formation, we developed a genetic system to conditionally express Wnt4 in chondrogenic tissues of the mouse. A mouse Wnt4 cDNA was introduced into the ubiquitously expressed Rosa26 (R26) locus by gene targeting in embryonic stem (ES) cells. The expression of Wnt4 from the R26 locus was blocked by a neomycin selection cassette flanked by loxP sites (floxneo) that was positioned between the Rosa26 promoter and the Wnt4 cDNA, creating the allele designated R26(floxneoWnt4). Wnt4 expression was activated during chondrogenesis using Col2a1-Cre transgenic mice that express Cre recombinase in differentiating chondrocytes. R26(floxneoWnt4); Col2a1-Cre double heterozygous mice exhibited a growth deficiency, beginning approximately 7 to 10 days after birth, that resulted in dwarfism. In addition, they also had craniofacial abnormalities, and delayed ossification of the lumbar vertebrae and pelvic bones. Histological analysis revealed a disruption in the organization of the growth plates and a delay in the onset of the primary and secondary ossification centers. Molecular studies showed that Wnt4 overexpression caused decreased proliferation and altered maturation of chondrocytes. In addition, R26(floxneoWnt4); Col2a1-Cre mice had decreased expression of vascular endothelial growth factor (VEGF). These studies demonstrate that Wnt4 overexpression leads to dwarfism in mice. The data indicate that Wnt4 levels must be regulated in chondrocytes for normal growth plate development and skeletogenesis. Decreased VEGF expression suggests that defects in vascularization may contribute to the dwarf phenotype

Luminescence of InGaN MQWs grown on misorientated GaN substrates

Optoelectronic devices based on InGaN have already been commercialised, however, the Indium content is limited to around 5%. With higher Indium concentration the quantum efficiency decreases, which is thought to be due to increasing inhomogeneity. In this work it is shown that the growth of InGaN on misorientated GaN substrates forces these Indium fluctuations on a nanometre scale. Temperature dependent luminescence measurements provide information about the homogeneity of the band structure. Energy selective excitation confirms the existence of localisation centres and indicates their energetic depth. Time-resolved measurements define the lifetime of localized excitons, which provides information about radiative and nonradiative processes as well as tunnelling mechanisms between the localization centres. Indium fluctuations at the nm and μm scale are measured using cathodoluminescence (CL) and Micro Photoluminescence (μPL) respectively. © 2010 IEEE