Igf1R/InsR function is required for axon extension and corpus callosum formation.

One of the earliest steps during the development of the nervous system is the establishment of neuronal polarity and the formation of an axon. The intrinsic mechanisms that promote axon formation have been extensively analyzed. However, much less is known about the extrinsic signals that initiate axon formation. One of the candidates for these signals is Insulin-like growth factor 1 (Igf1) that acts through the Igf1 (Igf1R) and insulin receptors (InsR). Since Igf1R and InsR may act redundantly we analyzed conditional cortex-specific knockout mice that are deficient for both Igf1r and Insr to determine if they regulate the development of the cortex and the formation of axons in vivo. Our results show that Igf1R/InsR function is required for the normal development of the embryonic hippocampus and cingulate cortex while the lateral cortex does not show apparent defects in the Igf1r;Insr knockout. In the cingulate cortex, the number of intermediate progenitors and deep layer neurons is reduced and the corpus callosum is absent at E17. However, cortical organization and axon formation are not impaired in knockout embryos. In culture, cortical and hippocampal neurons from Igf1r;Insr knockout embryos extend an axon but the length of this axon is severely reduced. Our results indicate that Igf1R/InsR function is required for brain development in a region-specific manner and promotes axon growth but is not essential for neuronal polarization and migration in the developing brain

Automatic performance optimization of the discrete Fourier transform on distributed memory computers

Abstract. This paper introduces a formal framework for automatically generating performance optimized implementations of the discrete Fourier transform (DFT) for distributed memory computers. The framework is implemented as part of the program generation and optimization system SPIRAL. DFT algorithms are represented as mathematical formulas in SPIRAL’s internal language SPL. Using a tagging mechanism and formula rewriting, we extend SPIRAL to automatically generate parallelized formulas. Using the same mechanism, we enable the generation of rescaling DFT algorithms, which redistribute the data in intermediate steps to fewer processors to reduce communication overhead. It is a novel feature of these methods that the redistribution steps are merged with the communication steps of the algorithm to avoid additional communication overhead. Among the possible alternative algorithms, SPIRAL’s search mechanism now determines the fastest for a given platform, effectively generating adapted code without human intervention. Experiments with DFT MPI programs generated by SPIRAL show performance gains of up to 30 % due to rescaling. Further, our generated programs compare favorably with FFTW-MPI 2.1.5.

The rodent Four-jointed ortholog Fjx1 regulates dendrite extension

AbstractThe extrinsic and intrinsic factors that regulate the size and complexity of dendritic arborizations are still poorly understood. Here we identify Fjx1, the rodent ortholog of the Drososphila planar cell polarity (PCP) protein Four-jointed (Fj), as a new inhibitory factor that regulates dendrite extension. The Drosophila gene four-jointed (fj) has been suggested to provide directional information in wing discs, but the mechanism how it acts is only poorly understood and the function of its mammalian homolog Fjx1 remains to be investigated. We analyzed the phenotype of a null mutation for mouse Fjx1. Homozygous Fjx1 mutants show an abnormal morphology of dendritic arbors in the hippocampus. In cultured hippocampal neurons from Fjx1 mutant mice, loss of Fjx1 resulted in an increase in dendrite extension and branching. Addition of Fjx1 to cultures of dissociated hippocampal neurons had the opposite effect and reduced the length of dendrites and decreased dendritic branching. Rescue experiments with cultured neurons showed that Fjx1 can act both cell-autonomously and non-autonomously. Our results identify Fjx1 as a new inhibitory factor that regulates dendrite extension