Using an eye phenotype assay that had been successful previously (see FBhh0001071), a gain-of-function mutation of Dmel\Raf has been characterized in combination with overexpression of Dmel\RhoGEF2. Co-expression in somatic clones within the eye-antennal disc results in clonal tissue overgrowth through an extended larval stage; large undifferentiated clonal masses are observed in the basal sections of the posterior region of the eye disc.
Rho family guanine nucleotide exchange factors (RhoGEFs) comprise a large and diverse family that mediate activation of Rho GTPases in many different developmental contexts. Dmel\RhoGEF2 is orthologous to three human genes, ARHGEF11, ARHGEF12, ARHGEF1. Classical amorphic and hypomorphic alleles, RNAi-targeting constructs, and alleles caused by insertional mutagenesis have been generated for Dmel\RhoGEF2. Animals homozygous for loss-of-functions mutations of RhoGEF2 die during the embryonic stage. These disease model experiments make use of a transgenic overexpression genotype in somatic clones.
None of three human genes orthologous to Dmel\RhoGEF2, ARHGEF11, ARHGEF12, or ARHGEF1, has been introduced into flies. Multiple constructs of the human Hsap\RAF1 have been introduced into flies, but have not been used in the context of this human disease model; see the human disease model report 'cancer, multiple, RAF1-related' (FBhh0000558).
Animals homozygous for amorphic mutations of Dmel\Raf exhibit lethality in the late larval stage; imaginal discs are undeveloped. Embryos lacking all Dmel\Raf activity (derived from homozygous null germline clones in the mother and not rescued by paternal contribution) die in early embryogenesis. Many genetic and physical interactions of Dmel\Raf have been described; see below and in the Raf gene report.
[updated Jul. 2019 by FlyBase; FBrf0222196]