This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Tubulogenesis, the morphogenesis of biological tubes, is required for the development and function of the gut, neural tube, and other organs and is evolutionarily conserved. A useful model for the study of tubulogenesis is dorsal appendage (DA) formation in the Drosophila egg chamber during oogenesis. The DAs are specialized eggshell structures that facilitate embryonic gas exchange. They are made by two patches of ~75 follicle cells, each composed of roof and floor cells that reorganize from a flat epithelium into tubes, extend anteriorly, form paddle-shaped structures at the anterior tips of the tubes, and secrete chorion into the tube lumens. During anterior extension of the DA tubes, roof and floor cells extend filopodia-like extensions towards their substrate;the squamous stretch follicle cells (SCs). Likewise, the SCs project cellular extensions toward the migrating DA-forming cells. In bullwinkle (bwk) mutants, patterning of the DA primordium occurs normally but the egg chamber forms moose-antler shaped DAs. A modifier screen identified shark, a tyrosine kinase, as a strong enhancer of the bwk phenotype. shark is required in the SCs for proper DA morphogenesis. The nature of the signal from the SCs to the DA forming cells is unknown. Knowledge of the genetic and signaling interactions and how they affect the behavior of the cells that form DA tubes will potentially shed light on human developmental processes such as neural tube defects and add to a growing body of knowledge that will lead to the prevention of birth defects in humans.
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