Dachs: an unconventional myosin that functions downstream of Fat to regulate growth, affinity and gene expression inDrosophila

Abstract

The dachs gene was first identified almost a century ago based on its requirements for appendage growth, but has been relatively little studied. Here, we describe the phenotypes of strong dachs mutations, report the cloning of the dachs gene, characterize the localization of Dachs protein, and investigate the relationship between Dachs and the Fat pathway. Mutation of dachs reduces, but does not abolish, the growth of legs and wings. dachs encodes an unconventional myosin that preferentially localizes to the membrane of imaginal disc cells. dachs mutations suppress the effects of fat mutations on gene expression, cell affinity and growth in imaginal discs. Dachs protein localization is influenced by Fat, Four-jointed and Dachsous, consistent with its genetic placement downstream of fat. However, dachs mutations have only mild tissue polarity phenotypes, and only partially suppress the tissue polarity defects of fat mutants. Our results implicate Dachs as a crucial downstream component of a Fat signaling pathway that influences growth, affinity and gene expression during development.

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

“…The efficiency of their heterodimer formation is modulated by a Golgi-localized protein kinase Fourjointed (Fj) (Villano and Katz, 1995;Matakatsu and Blair, 2004;Ishikawa et al, 2008), which phosphorylates Ft and Ds (Brittle et al, 2010;Simon et al, 2010). Ds-Ft are thought to be a ligand-receptor pair that acts via the atypical myosin Dachs (D) (Mao et al, 2006), whose localization in a cell reflects the Ft activity (Matakatsu and Blair, 2008;Rogulja et al, 2008). Both fj and ds are expressed in gradients in developing imaginal discs (Clark et al, 1995;Villano and Katz, 1995;Brodsky and Steller, 1996;Buckles et al, 2001).…”

“…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).…”

“…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). Ft, Ds, and Fj function together during the earlier stages of wing and leg development to control growth along the PD axis (Mao et al, 2006). Viable mutations in each of these three genes give rise to flies with defects in the ratio of PD to AP growth of the wing and leg (Bryant et al, 1988;Clark et al, 1995;Villano and Katz, 1995;Adler et al, 1998;Zeidler et al, 2000).…”

“…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.…”

“…Expression patterns of the three genes in the cricket leg bud are different from those in the wing imaginal disc. Although no intensive study has investigated their functions in the leg imaginal disc, these may be similar because phenotypes of their mutants are similar to the wing phenotypes (Mao et al, 2006). Although there is no evidence for a FtFt or Ds-Ds trans-homodimer formation in Drosophila cells, we hypothesized the presence of the trans-homophilic interactions of Ft or Ds in their higher concentration region in addition to the heterophilic interaction, as shown in Figure 5C, based on their expression patterns and their structures implying the presence of both homophilic and heterophilic interactions (Halbleib and Nelson, 2006).…”