Endogenous retroviruses and neighboring genes are coordinately repressed by LSD1/KDM1A.

Endogenous retroviruses (ERVs) constitute a substantial portion of mammalian genomes, and their retrotransposition activity helped to drive genetic variation, yet their expression is tightly regulated to prevent unchecked amplification. We generated a series of mouse mutants and embryonic stem (ES) cell lines carrying "deletable" and "rescuable" alleles of the lysine-specific demethylase LSD1/KDM1A. In the absence of KDM1A, the murine endogenous retrovirus MuERV-L/MERVL becomes overexpressed and embryonic development arrests at gastrulation.

Multi-photon imaging.

Multi-photon microscopy, now in its twentieth year, has developed into one of the most robust and powerful techniques for live cell and in vivo fluorescence imaging. Although its theoretical framework is nearly a century old, it has only become a practical tool for biological research with the development of ultrafast lasers and scanning microscopy techniques. In this unit, we outline the basic principles of multi-photon microscopy, paying special attention to technical considerations for biological applications.

Human host factors required for influenza virus replication.

Influenza A virus is an RNA virus that encodes up to 11 proteins and this small coding capacity demands that the virus use the host cellular machinery for many aspects of its life cycle. Knowledge of these host cell requirements not only informs us of the molecular pathways exploited by the virus but also provides further targets that could be pursued for antiviral drug development. Here we use an integrative systems approach, based on genome-wide RNA interference screening, to identify 295 cellular cofactors required for early-stage influenza virus replication.

Segregation of axial motor and sensory pathways via heterotypic trans-axonal signaling.

Execution of motor behaviors relies on circuitries effectively integrating immediate sensory feedback to efferent pathways controlling muscle activity. It remains unclear how, during neuromuscular circuit assembly, sensory and motor projections become incorporated into tightly coordinated, yet functionally separate pathways. We report that, within axial nerves, establishment of discrete afferent and efferent pathways depends on coordinate signaling between coextending sensory and motor projections.

Instructive role of aPKCzeta subcellular localization in the assembly of adherens junctions in neural progenitors.

In the neurogenic phase of CNS development, the proliferating progenitors are found medially within the neuroepithelium. The adherens junctions on the apical membrane of proliferating neural progenitors allow for cell-cell adhesion and medial stratification. In contrast, differentiating neuronal precursors delaminate and migrate laterally, establishing the laminar layers.

Coexpressed EphA receptors and ephrin-A ligands mediate opposing actions on growth cone navigation from distinct membrane domains.

Contact-dependent signaling between membrane-linked ligands and receptors such as the ephrins and Eph receptor tyrosine kinases controls a wide range of developmental and pathological processes. Paradoxically, many cell types coexpress both ligands and receptors, raising the question of how specific signaling readouts are achieved under these conditions. Here, we studied the signaling activities exerted by coexpressed EphA receptors and GPI-linked ephrin-A ligands in spinal motor neuron growth cones.