How Notch establishes longitudinal axon connections between successive segments of the Drosophila CNS.

Development of the segmented central nerve cords of vertebrates and invertebrates requires connecting successive neuromeres. Here, we show both how a pathway is constructed to guide pioneer axons between segments of the Drosophila CNS, and how motility of the pioneers along that pathway is promoted. First, canonical Notch signaling in specialized glial cells causes nearby differentiating neurons to extrude a mesh of fine projections, and shapes that mesh into a continuous carpet that bridges from segment to segment, hugging the glial surface.

Noncanonical Notch function in motor axon guidance is mediated by Rac GTPase and the GEF1 domain of Trio.

The receptor Notch interacts with the Abl tyrosine kinase signaling pathway to control axon growth and guidance in Drosophila motor neurons. In part, this is mediated by binding to Trio, a guanine nucleotide exchange factor (GEF) for Rho GTPases. We show here that one of the two GEF domains of Trio, the Rac-specific GEF1, is essential for Trio-dependent motor axon guidance and for the genetic suppression of Notch function in motor axon patterning, but the Rho-specific GEF2 domain is not.

Disabled is a bona fide component of the Abl signaling network.

Abl is an essential regulator of cell migration and morphogenesis in both vertebrates and invertebrates. It has long been speculated that the adaptor protein Disabled (Dab), which is a key regulator of neuronal migration in the vertebrate brain, might be a component of this signaling pathway, but this idea has been controversial. We now demonstrate that null mutations of Drosophila Dab result in phenotypes that mimic Abl mutant phenotypes, both in axon guidance and epithelial morphogenesis.

The receptor protein tyrosine phosphatase PTP69D antagonizes Abl tyrosine kinase to guide axons in Drosophila.

During Drosophila embryogenesis, both the cytoplasmic Abelson tyrosine kinase (Abl) and the membrane bound tyrosine phosphatase PTP69D are required for proper guidance of CNS and motor axons. We provide evidence that PTP69D modulates signaling by Abl and its antagonist, Ena. An Abl loss-of function mutation dominantly suppresses most Ptp69D mutant phenotypes including larval/pupal lethality and CNS and motor axon defects, while increased Abl and decreased Ena expression dramatically increase the expressivity of Ptp69D axonal defects.

Heat shock protein 27 is associated with irinotecan resistance in human colorectal cancer cells.

Heat shock protein (Hsp) in tumor cells has been proposed to enhance their resistance to chemotherapeutic agents. In the present study, we investigated the influence of Hsp expression on the irinotecan resistance of human colorectal cancer cells. Among eight Hsp genes tested in this study, we confirmed that the expression of Hsp27 correlated with irinotecan resistance in colorectal cancer cells.