Clinical irradiation of the brain induces hippocampus-dependent cognitive impairments in some but not all individuals, suggesting the involvement of genetic risk factors. Deficiency of apolipoprotein E (APOE), which is important for the metabolism and redistribution of lipoproteins and cholesterol, increases behavioral impairments after irradiation, supporting a protective role for APOE against radiation-induced cognitive injury. Compared to APOE3, APOE4 increases while APOE2 decreases the risk of developing age-related cognitive decline and Alzheimer's disease, particularly in women. To determine the potential effects of APOE isoform and sex on radiation-induced cognitive impairments, we irradiated 2-month-old male and female APOE2, APOE3 and APOE4 mice and assessed their cognitive performance 3 months later. When hippocampus-dependent spatial learning and memory were assessed in the water maze, sham-irradiated female APOE2, APOE3 and APOE4 and irradiated female APOE2 mice showed spatial memory retention, but irradiated female APOE3 and APOE4 mice did not. Compared to sham-irradiated female APOE4 mice, irradiated female APOE4 mice also required more trials to reach criterion in the hippocampus-dependent passive avoidance test. Radiation had no effects on water maze or passive avoidance learning and memory of male APOE2, APOE3 or APOE4 mice, indicating that the effects of radiation on cognitive performance are dependent on sex- and APOE isoform.

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Similar to chick, mouse, and Xenopus, a number of intercellular signaling pathways are required for zebrafish segmentation. However, the spatial scales over which these signaling pathways operate in zebrafish remain largely unknown. During zebrafish segmentation, waves of her1 transcription (a) initiate within the tailbud region, (b) propagate anteriorly through presomitic mesoderm (PSM), and (c) terminate in the anlage of newly-forming somites. These observations raise the question of whether the tailbud region serves as a "pacemaker" or "organizing center" for the initiation of propagating her1 expression waves. Microsurgical manipulations reveal that the anteriorly waves of her1 transcription are not perturbed by removal of the zebrafish tailbud. Furthermore, expression patterns of deltaD, paraxial protocadherin C (papc), and myoD within recently formed somites also appear to be relatively unperturbed by either removal of the tailbud, or by removal of lateral plate mesoderm. Although dynamic gene networks rapidly specify mesenchymal or epithelial cellular identities within forming somites, this specification is plastic. Time-lapse analysis has shown that the cellular progeny of mitotically-active epithelial border cells within newly formed somites can adopt different cellular identities than their precursor cells. Overall, these results indicate that sustained long-range intercellular communication with the tailbud, anterior somites, or lateral plate mesoderm is not necessary for segmentation or somitogenesis to proceed within the PSM. The basic segmentation and somitogenesis processes in zebrafish presomitic mesoderm appear to be largely regionally autonomous and governed by local morphogenetic cell behaviors.