Cell behaviour of Drosophila fat cadherin mutations in wing development

Abstract

We have studied several cell behaviour parameters of mutant alleles of fat (ft) in Drosophila imaginal wing disc development. Mutant imaginal discs continue growing in larvae delayed in pupariation and can reach sizes of several times those of wild-type. Their growth is, however, basically allometric. Homozygous ft cells grow faster than their twin cells in clones and generate larger territories, albeit delimited by normal clonal restrictions. Moreover, ft cells in clones tend to grow towards wing proximal regions. These behaviours can be related with failures in cell adhesiveness and cell recognition. Double mutant combinations with alleles of other genes, e.g. of the Epidermal growth factor receptor (DER) pathway, modify ft clonal phenotypes, indicating that adhesiveness is modulated by intercellular signalling. Mutant ft cells show, in addition, smaller cell sizes during proliferation and abnormal cuticular differentiation, which reflect cell membrane and cytoskeleton anomalies, which are not modulated by the DER pathway.

Cell packing influences planar cell polarity signaling

“…However, we observe no fat dependent alteration of E-cadherin expression as has been observed in the wing imaginal disk (31), and Crumbs localization and levels appear normal in fat clones (not shown), implying that there is no obvious defect in junctional complex formation. One possible explanation is the excess proliferation that occurs within fat clones, as suggested by previous results (32), and this is consistent with the observation that suppression of hyperproliferation by overexpressing Warts partially suppresses the polarity disruption phenotype (33). fat clones in 18-h APF pupal wings often have higher cell density than surrounding tissue (data not shown).…”

Regulation of leg size and shape: Involvement of the Dachsous‐fat signaling pathway

“…6). This is consistent with the fact that Drosophila mutant phenotypes of both ft and ds have short and thick adult legs, despite the fact that ft and ds have distinct expression patterns in Drosophila imaginal discs (Garoia et al, 2000;Ma et al, 2003). These results were not expected if Ds and Ft acted as a traditional ligand and receptor.…”

“…In the wing disc, ds is highly expressed in proximal regions, and fj is expressed distally, whereas ft is expressed uniformly throughout the disc (Fig. 4) (Garoia et al, 2000;Mao et al, 2006;Reddy and Irvine, 2008). Since uniform misexpression of Fj and Ds in the wing disc inhibits cell proliferation and growth, graded expression of Ft regulators such as Fj and Ds could modulate Ft signaling by polarizing Ft activity within the cell (Rogulja et al, 2008;Willecke et al, 2008).…”

“…Wings and legs of flies with viable ft alleles display overgrowth mostly in the AP direction ( Fig. 2) (Garoia et al, 2000;Mao et al, 2006). The defects caused by ft, ds, and fj mutations suggest that they are involved in regulating growth differences along both AP and PD axes.…”

Identification of homozygous deletions of tumor suppressor gene FAT in oral cancer using CGH-array

“…Its deletion causes hyperplastic overgrowth of larval imaginal discs, and defects in differentiation and morphogenesis (Bryant et al, 1988;Mahoney et al, 1991). Of particular interest is the fact that FAT interacts with components of the EGFR pathway in Drosophila (Garoia et al, 2000). Sequencing analysis of full-length cDNA revealed that the FAT gene encodes a huge protein (27 exons, 4590 amino acids, 506 kDa) with 34 cadherin-like domains, five EGF-like repeats interspersed with two laminin A-G chain motifs, a transmembrane domain and a novel cytoplasmic domain (Mahoney et al, 1991;Ponassi et al, 1999).…”