Cadherin Cad99C is regulated by Hedgehog signaling in Drosophila

Abstract

The subdivision of the Drosophila wing imaginal disc into anterior and posterior compartments requires a transcriptional response to Hedgehog signaling. However, the genes regulated by Hedgehog signal transduction that mediate the segregation of anterior and posterior cells have not been identified. Here, we molecularly characterize the previously predicted gene cad99C and show that it is regulated by Hedgehog signaling. Cad99C encodes a transmembrane protein with a molecular weight of approximately 184 kDa that contains 11 cadherin repeats in its extracellular domain and a conserved type I PDZ-binding site at its C-terminus. The levels of cad99C RNA and protein are low throughout the wing imaginal disc. However, in the pouch region, these levels are elevated in a strip of anterior cells along the A/P boundary where the Hedgehog signal is transduced. Ectopic expression of Hedgehog, or the Hedgehog-regulated transcription factor Cubitus interruptus, induces high-level expression of Cad99C. Conversely, blocking Hedgehog signal transduction by either inactivating Smoothened or Cubitus interruptus reduces high-level Cad99C expression. Finally, by analyzing mutant clones of cells, we show that Cad99C is not essential for cell segregation at the A/P boundary. We conclude that cad99C is a novel Hedgehog-regulated gene encoding a member of the cadherin superfamily in Drosophila.

Interplay between Rab5 and PtdIns(4,5)P2 controls early endocytosis in theDrosophilagermline

“…2D). These structures might correspond to actin bundles, as they resemble these structures that are observed, for instance, in the apical microvilli of follicle cells (D'Alterio et al, 2005;Schlichting et al, 2006) (supplementary material Fig. S1G,H).…”

“…2B). It is important to note that the electron-dense material found between the oocyte and the follicle cells does not correspond to yolk protein prior to its uptake by the oocyte but rather to vitelline bodies (v), which remain in the perivitelline space and will coalesce at the end of stage 10 to form the vitelline membrane around the oocyte (D'Alterio et al, 2005;Schlichting et al, 2006).…”

Ventral specification and perturbed boundary formation in the mouse midbrain in the absence of Hedgehog signaling

“…A loss of the spatial coherence of pattern and poorly defined tissue boundaries following HH perturbations have been previously reported in the fly wing and the vertebrate neural tube, including the chick midbrain (Dahmann and Basler, 1999;Lawrence et al, 1999;Bai et al, 2004;Agarwala et al, 2005;Bayly et al, 2007). This disruption has been attributed to the regulation of cell-affinities by HH signaling (Dahmann and Basler, 1999;Jarov et al, 2003;Schlichting et al, 2005). We, therefore, conclude that the most likely explanation for the cell scatter seen at the MHB and RP is a disruption of cell affinities, although we cannot definitively rule out the ectopic expression of RP and MHB markers in midbrain cells away from the MHB and the RP in the absence of HH signaling.…”

Myosin VIIA regulates microvillus morphogenesis and interacts with cadherin Cad99C in Drosophila oogenesis

“…Finger-like protrusions called microvilli are often found on the apical surface of epithelial cells. The microvilli of the ovarian follicular epithelium in Drosophila are a prominent example (Mahowald and Kambysellis, 1980;Trougakos et al, 2001;D'Alterio et al, 2005;Schlichting et al, 2006). Furthermore, microvilli can give rise to complex structures in sensory organs, such as rhabdomeres and bristles in insects and hair cell stereocilia in the vertebrate ear, which transduce light and mechanosensory stimuli, respectively (reviewed by DeRosier and Tilney, 2000;Frolenkov et al, 2004).…”

“…In the absence of Cad99C, the brush border develops severe defects, including shortened or collapsed and irregularly distributed microvilli. By contrast, overexpression of Cad99C led to highly elongated microvilli (D'Alterio et al, 2005;Schlichting et al, 2006). To better understand how this cadherin regulates microvillus structure and brush border organization, we looked for interaction partners.…”