D-JNK signaling in visceral muscle cells controls the laterality of the Drosophila gut

Abstract

Although bilateral animals appear to have left-right (LR) symmetry from the outside, their internal organs often show directional and stereotypical LR asymmetry. The mechanisms by which the LR axis is established in vertebrates have been extensively studied. However, how each organ develops its LR asymmetric morphology with respect to the LR axis is still unclear. Here, we showed that Drosophila Jun N-terminal kinase (D-JNK) signaling is involved in the LR asymmetric looping of the anterior-midgut (AMG) in Drosophila. Mutant embryos of puckered (puc), which encodes a D-JNK phosphatase, showed random laterality of the AMG. Directional LR looping of the AMG required D-JNK signaling to be down-regulated by puc in the trunk visceral mesoderm. Not only the down-regulation, but also the activation of D-JNK signaling was required for the LR asymmetric looping. We also found that the LR asymmetric cell rearrangement in the circular visceral muscle (CVM) was regulated by D-JNK signaling and required for the LR asymmetric looping of the AMG. Rac1, a Rho family small GTPase, augmented D-JNK signaling in this process. Our results also suggest that a basic mechanism for eliciting LR asymmetric gut looping may be conserved between vertebrates and invertebrates.

The development and evolution of left‐right asymmetry in invertebrates: Lessons from Drosophila and snails

“…Our results showed that the mesodermal tissue also plays an essential role in the LR asymmetric development of the anterior midgut in D. melanogaster (Taniguchi et al, 2007b). Therefore, mechanisms of the mesoderm-derived LR asymmetric morphogenesis of the gut may be conserved between vertebrates and invertebrates.…”

“…This result suggests that Rac1 acts upstream of D-JNK signaling in the LR asymmetric rearrangement of the visceral muscle cells (Taniguchi et al, 2007b).…”

“…By genetic screening, Hozumi et al (2006), Maeda et al (2007), and Taniguchi et al (2007b) found that three genes, single-minded (sim), puckered (puc), and Myosin31DF (Myo31DF) are all required for the normal LR asymmetric development of the embryonic gut (Table 1). sim is expressed in ventral midline cells and required for the differentiation of these cells (Nambu et al, 1991).…”

“…However, the precise role of the embryonic midline cells in this process in D. melanogaster remains unknown. The puckered (puc) mutation randomizes the LR polarity of the embryonic anterior midgut (Taniguchi et al, 2007b). puc encodes a Jun N-terminal kinase (JNK) phosphatase and is required for the LR asymmetric rearrangement of the visceral muscle cells, which seems to be important for the normal directional looping of the anterior midgut (Taniguchi et al, 2007b).…”

“…The puckered (puc) mutation randomizes the LR polarity of the embryonic anterior midgut (Taniguchi et al, 2007b). puc encodes a Jun N-terminal kinase (JNK) phosphatase and is required for the LR asymmetric rearrangement of the visceral muscle cells, which seems to be important for the normal directional looping of the anterior midgut (Taniguchi et al, 2007b). Thus, the appropriate regulation of D. melanogaster JNK (D-JNK) signaling is needed for normal LR asymmetry of the anterior midgut.…”