Mtlinteracts with members of Egfr signaling and cell adhesion genes in the Drosophila eye

Abstract

Mtl is a member of the Rho family of small GTPases in Drosophila. It was shown that Mtl is involved in planar cell polarity (PCP) establishment, together with other members of the same family like Cdc42, Rac1, Rac2 and RhoA. However, while Rac1, Rac2 and RhoA function downstream of Dsh in Fz/PCP signaling and upstream of a JNK cassette, Mtl and Cdc42 do not. To determine the functional context of Mtl during PCP establishment in the Drosophila eye, we performed a loss-of-function screen to search for dominant modifiers of a sev>Mtl rough eye phenotype. In addition, genetic interaction assays with candidate genes were also carried out. Our results show that Mtl interacts genetically with members and effectors of Egfr signaling, with components and/or regulators of other signal transduction pathways, and with genes involved in cell adhesion and cytoskeleton organization. One of these genes is hibris (hbs), which encodes a member of the immunoglobulin superfamily in Drosophila. Phenotypic analyses and genetic interaction assays suggest that it may have a role during PCP establishment, interacting with both Egfr and Fz/PCP signaling during this process. Taken together, our results indicate that Mtl is functionally related to the Egfr pathway regulating ommatidial rotation during PCP establishment in the eye, being a positive regulator of this pathway. Since Egfr signaling is linked to cytoskeletal and cell junctional elements, it is likely that Mtl may be regulating cytoskeleton dynamics and thus cell adhesion during ommatidial rotation in the context of that pathway.

Unique and Overlapping Functions of Formins Frl and DAAM During Ommatidial Rotation and Neuronal Development in Drosophila

“…Unfortunately, eye clones of cdc42 null mutant cells cannot be recovered (Genova et al 2000;Muñoz-Descalzo et al 2007), but a hypomorphic cdc42 allele shows mild rotation defects in the eye similar in strength to loss of frl (2.9 6 3.8%), and the mild PCP phenotype of rac1 and its paralogs rac2 and mtl in triple mutant clones are enhanced in a cdc42 hypomorphic background, suggesting that these GTPases contribute to PCP signaling in a partially redundant manner (Muñoz-Descalzo et al 2007). Cdc42 also acts together with Mtl (Muñoz-Descalzo et al 2007;Muñoz-Soriano et al 2011), which is regulated by EGFR signaling that is known to control ommatidial rotation (Brown and Freeman 2003;Gaengel and Mlodzik 2003;Strutt and Strutt 2003). While we present evidence that Cdc42 regulates Frl during PCP signaling in the eye, we failed to detect genetic interactions between sep .…”

Transcriptional Activity and Nuclear Localization of Cabut, the Drosophila Ortholog of Vertebrate TGF-β-Inducible Early-Response Gene (TIEG) Proteins

“…Ovaries were dissected as described [45] and stained using the anti-CbtΔZn antibody [13]. Scanning electron microscopy analysis of adult eyes was performed following the critical point dry method using a Hitachi S4100 microscope, as previously described [46].…”

Hibris, a Drosophila Nephrin Homolog, Is Required for Presenilin-Mediated Notch and APP-like Cleavages

“…This cell adhesion function of Hbs has been implicated in embryonic myogenesis and late pupal eye patterning (Artero et al, 2001; Bao and Cagan, 2005; Dworak et al, 2001). Recently it has also been suggested that hbs acts in PCP establishment through its genetic interaction with Mtl, a member of the Rho GTPase subfamily (Munoz-Soriano et al, 2011), though the mechanism(s) by which Hbs might influence PCP have not been addressed.…”