Collapsin response mediator protein 2, CRMP2, has been identified as an intracellular signaling mediator for Semaphorin 3A (Sema3A). CRMP2 plays a key role in axon guidance, dendritic morphogenesis, and cell polarization. It has been also implicated in a variety of neurological and psychiatric disorders. However, the in vivo functions of CRMP2 remain unknown. We generated CRMP2 gene-deficient (crmp2 À/À ) mice. The crmp2 À/À mice showed irregular development of dendritic spines in cortical neurons. The density of dendritic spines was reduced in the cortical layer V pyramidal neurons of crmp2 À/À mice as well as in those of sema3A À/À and crmp1 À/À mice. However, no abnormality was found in dendritic patterning in crmp2 À/À compared to wild-type (WT) neurons. The level of CRMP1 was increased in crmp2, but the level of CRMP2 was not altered in crmp1 À/À compared to WT cortical brain lysates.Dendritic spine density and branching were reduced in double-heterozygous sema3A +/À ;crmp2 +/À and sema3A +/À ;crmp1 +/À mice. The phenotypic defects had no genetic interaction between crmp1 and crmp2. These findings suggest that both CRMP1 and CRMP2 mediate Sema3A signaling to regulate dendritic spine maturation and patterning, but through overlapping and distinct signaling pathways.

Free dihomo-γ-linolenic acid (DGLA), a polyunsaturated free fatty acid (FFA), can potentially be used to produce eicosanoid pharmaceuticals, such as prostaglandin E1. Previously, we constructed an Aspergillus oryzae mutant strain, named DGLA3, which produced free DGLA at an increased yield by faaA gene disruption and co-overexpression of one elongase and two desaturase genes. In this study, we achieved further increase. Since FFA production is increased by enhancing the pentose phosphate pathway, we overexpressed a predicted transketolase gene composing the pathway in DGLA3, which consequently increased the free DGLA yield by 1.9-fold to 403 mg/L. Additionally, we disrupted the α-1,3-glucan synthase gene agsB involved in cell-wall biosynthesis, which further increased it by 1.3-fold to 533 mg/L. Overall, the yield increased by 2.5-fold. Free DGLA productivity and biomass increased similarly, but residual glucose concentration decreased. Increased hyphal dispersion appeared to cause additional glucose consumption, resulting in an increase in biomass and yield.