Development of neural circuitry depends on the integration of signaling pathways to coordinate specification, proliferation and differentiation of cell types in the right number, in the right place, at the right time. Zinc finger protein 423 (Zfp423), a 30-zinc finger transcription factor, forms alternate complexes with components of several developmental signaling pathways, suggesting it as a point of signal integration during brain development. We previously showed that mice lacking Zfp423 have reduced proliferation of cerebellar precursor cells, resulting in complete loss of vermis and variable hypoplasia of cerebellar hemispheres. Here, we show that Zfp423(-/-) hemisphere malformations are shaped by both genetic and non-genetic factors, producing distinct phenotype distributions in different inbred genetic backgrounds. In genetic mapping studies, we identify four additive modifier loci (Amzn1-4) and seven synthetically interacting loci (Smzn1.1-3.1) that together explain approximately one-third of the phenotypic variance. Strain-specific sequence polymorphism and expression data provide a reduced list of functional variant candidate genes at each modifier locus. Environmental covariates add only modest explanatory power, suggesting an additional stochastic component. These results provide a comprehensive analysis of sources of phenotype variation in a model of hindbrain malformation.

Phosphatidylinositol transfer proteins (PITPs) mediate lipid signaling and membrane trafficking in eukaryotic cells. Loss-of-function mutations of the gene encoding PITPa in mice result in a range of dosagesensitive phenotypes, including neurological dysfunction, neurodegeneration, and premature death. We have previously reported genetic suppression of a strong hypomorphic allele, vibrator, by a wild-derived variant of Nxf1, which increases the level of PITPa made from vibrator alleles and suppresses each of the neurological and survival phenotypes. Here we report discovery and genetic mapping of additional vibrator modifiers, Mvb2 and Mvb3, from a different strain background that suppresses juvenile lethality without suppressing visible phenotypes or gene expression. Genotype-specific survival analysis predicts molecular heterosis at Mvb3. These results indicate a mechanism of suppression that bypasses a quantitative requirement for PITPa function.

. He has mainly worked in the field of photonic components. With about 400 publications and conference papers as well as about ten patents, he has made contributions to research on III-V semiconductor laser diodes, passive guided wave and grating devices, and to the design and fabrication of photonic ICs. He leads the Photonics Research Group, Ghent University-INTEC (associated lab of IMEC), which focuses on new concepts for optoelectronic components for optical communication, optical interconnect, and optical sensing. This includes the design, fabrication, and characterization of new devices fabricated in the clean room facility at Ghent University or in collaboration with third parties. He has been involved in a number of European research projects and has been the Coordinator of several of them. He currently coordinates the European Network of Excellence ePIXnet on photonic integrated components and circuits. At Ghent University, he is teaching courses relating to optoelectronics, photonics, and optical fiber communication for electrical engineering and applied physics engineering students. He has been chairing the electrical engineering educational committee of the Faculty of Applied Sciences (1996Sciences ( -2000 and currently chairs the Faculty's Research Committee. He has served as a member of the program committee of the ESSDERC