Receptor tyrosine kinases (RTKs) mediate distinct biological responses by stimulating similar intracellular signaling pathways. Whether the specificity of the response is determined by qualitative or quantitative differences in signaling output is not known. We addressed this question in vivo by replacing the multifunctional docking sites of Met, the receptor for hepatocyte growth factor, with ...

In Arabidopsis (Arabidopsis thaliana), ethylene responses are mediated by a family of five receptors that have both overlapping and nonoverlapping roles. In this study, we used loss-of-function mutants for each receptor isoform to determine the role of individual isoforms in seed germination under salt stress. From this analysis, we found subfunctionalization of the receptors in the control of ...

We have used rats and mice with mutations in myosin-Va to evaluate the range and function of IP3-mediated Ca2+ signaling in dendritic spines. In these mutants, the endoplasmic reticulum and its attendant IP3 receptors do not enter the postsynaptic spines of parallel fiber synapses on cerebellar Purkinje cells. Long-term synaptic depression (LTD) is absent at the parallel fiber synapses of the m...

Numb and Numblike, conserved homologs of Drosophila Numb, have been implicated in cortical neurogenesis; however, analysis of their involvement in later stages of cortical development has been hampered by early lethality of double mutants in previous studies. Using Emx1(IREScre) to induce more restricted inactivation of Numb in the dorsal forebrain of numblike null mice beginning at E9.5, we ha...

Autism spectrum disorders (ASDs) are complex and heterogeneous developmental disabilities affecting an ever-increasing number of children worldwide. The diverse manifestations and complex, largely genetic aetiology of ASDs pose a major challenge to the identification of unifying neuropathological features. Here we describe the neurodevelopmental defects in mice that carry deleterious alleles of...

The pathways leading from aberrant Prion protein (PrP) metabolism to neurodegeneration are poorly understood. Some familial PrP mutants generate increased (Ctm)PrP, a transmembrane isoform associated with disease. In other disease situations, a potentially toxic cytosolic form (termed cyPrP) might be produced. However, the mechanisms by which (Ctm)PrP or cyPrP cause selective neuronal dysfuncti...

Plexin-B2 deletion leads to aberrant lamination of cerebellar granule neurons (CGNs) and Purkinje cells. Although in the cerebellum is only expressed by proliferating CGN precursors outer external layer (oEGL), its function development still elusive. Here, we used 3D imaging, vivo electroporation live-imaging techniques study novel cerebellum-specific Plxnb2 conditional knockout mice. We show t...

Transformation of mechanical energy into electrical signals in mechanosensory neurons is essential for mechanosensation and nociception. This transformation occurs via sensory transduction channels that are activated by external force. Recent genetic and electrophysiological studies in Caenorhabditis elegans have directly shown that the degenerin/epithelial sodium channel (DEG/ENaC) ion channel...