Publications by authors named "Christopher M Meighan"

Integrins are involved in a vast number of cell behaviors due to their roles in adhesion and signaling. The regulation of integrin expression is of particular interest as a mechanism to drive developmental events and for the role of altered integrin expression profiles in cancer. Dynamic regulation of the expression of integrin receptors is required for the migration of the distal tip cell (DTC) during gonadogenesis in Caenorhabditis elegans.

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Integrin signaling relies on multiple, distinct pathways to impact a diverse set of cell behaviors. The Rho family of GTPases are well-established downstream signaling partners of integrins that regulate cell shape, polarity, and migration. The nematode C.

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Integrin signaling impacts many developmental processes. The complexity of these signals increases when multiple, unique integrin heterodimers are expressed during a single developmental event. Since integrin heterodimers have different signaling capabilities, the signals originating at each integrin type must be separated in the cell.

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Integrin receptors for extracellular matrix (ECM) are critical determinants of biological processes. Regulation of integrin expression is one way for cells to respond to changes in the ECM, to integrate intracellular signals, and to obtain appropriate adhesion for cell motility, proliferation, and differentiation. Transcriptional and post-translational mechanisms for changing the integrin repertoire at the cell surface have recently been described.

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Integrin receptors for extracellular matrix are critical for cell motility, but the signals that determine when to stop are not known. Analysis of distal tip cell (DTC) migration during gonadogenesis in Caenorhabditis elegans has revealed the importance of transcription factor vab-3/Pax6 in regulating the alpha integrin genes, ina-1 and pat-2. Utilizing vab-3 mutants, we show that the down-regulation of ina-1 is necessary for DTC migration cessation and the up-regulation of pat-2 is required for directionality.

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Gonad morphogenesis in Caenorhabditis elegans requires two secreted proteases. Recent studies show that alterations of the extracellular matrix component fibulin-1 rescue gonadogenesis in the absence of these proteases. This finding is a critical step toward understanding the role of extracellular matrix in organogenesis.

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Initiation of excretory system development in all vertebrates requires (1) delamination of the pronephric and pronephric duct rudiments from intermediate mesoderm at the ventral border of anterior somites, and (2) extension of the pronephric duct to the cloaca. Pronephric duct extension is the central event in nephric system development; the pronephric duct differentiates into the tubule that carries nephric filtrate out of the body and induces terminal differentiation of adult kidneys. Early studies concluded that pronephric ducts formed by means of in situ segregation of pronephric duct tissue from lateral mesoderm ventral to the forming somites; more recent studies highlight caudal migration of the pronephric duct as the major morphogenetic mechanism.

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