Regulation of repulsion versus adhesion by different splice forms of an Eph receptor

Eph tyrosine kinase receptors and their membrane-bound ephrin ligands mediate cell interactions and participate in several developmental processes. Ligand binding to an Eph receptor results in tyrosine phosphorylation of the kinase domain, and repulsion of axonal growth cones and migrating cells. Here we report that a subpopulation of ephrin-A5 null mice display neural tube defects resembling anencephaly in man. This is caused by the failure of the neural folds to fuse in the dorsal midline, suggesting that ephrin-A5, in addition to its involvement in cell repulsion, can participate in cell adhesion. During neurulation, ephrin-A5 is co-expressed with its cognate receptor EphA7 in cells at the edges of the dorsal neural folds. Three different EphA7 splice variants, a full-length form and two truncated versions lacking kinase domains, are expressed in the neural folds. Co-expression of an endogenously expressed truncated form of EphA7 suppresses tyrosine phosphorylation of the full-length EphA7 receptor and shifts the cellular response from repulsion to adhesion in vitro. We conclude that alternative usage of different splice forms of a tyrosine kinase receptor can mediate cellular adhesion or repulsion during embryonic development.     

Mutations in T-cell antigen receptor genes alpha and beta block thymocyte development at different stages.

Analysis of mice carrying mutant T-cell antigen receptor (TCR) genes indicates that TCR-beta gene rearrangement or expression is critical for the differentiation of CD4-CD8- thymocytes to CD4+CD8+ thymocytes, as well as for the expansion of the pool of CD4+CD8+ cells. TCR-alpha is irrelevant in these developmental processes. The development of gamma delta T cells does not depend on either TCR-alpha or TCR-beta.     

Origin and fate of Lake Vostok water frozen to the base of the East Antarctic ice sheet

The subglacial Lake Vostok may be a unique reservoir of genetic material and it may contain organisms with distinct adaptations, but it has yet to be explored directly. The lake and the overlying ice sheet are closely linked, as the ice-sheet thickness drives the lake circulation, while melting and freezing at the ice-sheet base will control the flux of water, biota and sediment through the lake. Here we present a reconstruction of the ice flow trajectories for the Vostok core site, using ice-penetrating radar data and Global Positioning System (GPS) measurements of surface ice velocity. We find that the ice sheet has a significant along-lake flow component, persistent since the Last Glacial Maximum. The rates at which ice is frozen (accreted) to the base of the ice sheet are greatest at the shorelines, and the accreted ice layer is subsequently transported out of the lake. Using these new flow field and velocity measurements, we estimate the time for ice to traverse Lake Vostok to be 16,000-20,000 years. We infer that most Vostok ice analysed to date was accreted to the ice sheet close to the western shoreline, and is therefore not representative of open lake conditions. From the amount of accreted lake water we estimate to be exported along the southern shoreline, the lake water residence time is about 13,300 years.     

Effects of beta-hydroxybutyrate on rat embryos grown in culture

In order to investigate further the relationship between maternal diabetes and fetal malformation, rat embryos were grown in vitro in the presence of beta-hydroxybutyrate, one of the ketone bodies produced by diabetics. At 10 mM, beta-hydroxybutyrate produced minor abnormalities and at 20 mM it produced major abnormalities in rat embryos.