Hox Gene AbdB controls left right asymmetry in Drosophila – Part II
Extending further from their work published in Nature journal, Noselli’s lab led by Jean-Baptiste Coutelis showed that Hox gene Abd-B controls the earliest steps of Drosophila left/right asymmetry establishment by directly binding to dextral determinant-encoding gene myoID .
The authors started the study by a genetic screen to find for more integrators of MyoID gene. They crossed many deficiency lines (Drosophila stocks with large deletions in chromosomes – survives in heterozygous condition by virtue of balancer chromosome) with viable myoIDK2 null strain, which shows no visible phenotype in heterozygous condition. The logic behind this genetic cross is that if the gene missing in deficiency line happens to interact with MyoID gene for establishing LR asymmetry, then we see a phenotype (rotated genitalia) in otherwise normal looking MyoID K2 flies in heterozygous condition.From the screen they found three fly lines showing rotated genitalia phenotype. One deficiency stock lacks MyoID, which served as a positive control for screen and other deficiency line gave the lead towards role of Hox gene AbdB as a regulator of MyoID gene and role in LR asymmetry. Later by using various genetics and biochemical experiments it was demonstrated that AbdB directly regulates MyoID . Loss of AbdB by means of RNAI technique and led to loss of MyosID expression showing that AbdB function is required for MyoID expression. This experiment was further validated by expressing ectopic AbdB (m isoform ) and RNAi AbdB in clones. The autors performed chip experiment and demonstrated that AbdB can bind directly to MyoID regulatory sequences.
Next they wanted to see whether AbdB mediated LR asymmetry is restricted to genitalia rotaion or also hold true for other asymmetric organ like embryonic gut. Genetic removal of AbdB from embryonic gut led to linearization of gut and proper looped hindgut was observed upon over expression of MyoID in AbdB depleted embryos. This experiment clearly show that AbdB controls LR asymmetry of embryonic gut of both males and females along with gentitalia rotation in males.
One common feature of both examples ( male genitalia rotation and hindgut looping ) is that MyoID is sufficient to rescue the phenotype caused by lack of AbdB . This clearly demonstrates that Abd-B depleted tissues are still competent for LR asymmetry but lack the directional cue of a LR determinant.
This work shows that in Drosophila, the Hox gene Abd-B, known for providing segment identity along AP axis possesses an additional and separate function of controlling initial steps of LR asymmetry determination (without AbdB symmetrical structures are formed) of the embryonic hindgut and male genitalia.
Coutelis JB, Géminard C, Spéder P, Suzanne M, Petzoldt AG, Noselli S.
Dev Cell. 2013 Jan 14;24(1):89-97. doi: 10.1016/j.devcel.2012.11.013.