Authors
Wanzhong GE, Yawen CHEN, Ruifen WENG, Sing Fee LIM, Marita BUESCHER, R ZHANG and Stephen M COHEN.

Institute of Molecular Cell Biology, 61 Biopolis Drive, Singapore 138673, Singapore

Published in Cell Death Differ. 2011 Nov 18. doi: 10.1038/cdd.2011.161.
[Epub ahead of print]

Abstract

Regulation of apoptosis is crucial for tissue homeostasis under normal development and environmental stress. In Drosophila, cell death occurs in different developmental processes including embryogenesis. Here, we report that two members of the miR-2 seed family of microRNAs, miR-6 and miR-11, function together to limit the level of apoptosis during Drosophila embryonic development. Mutants lacking both miR-6 and miR-11 show embryonic lethality and defects in the central nervous system (CNS). We provide evidence that miR-6/11 functions through regulation of the proapoptotic genes, reaper (rpr), head involution defective (hid), grim and sickle (skl). Upregulation of these proapoptotic genes is responsible for the elevated apoptosis and the CNS defects in the mutants. These findings demonstrate that the activity of the proapoptotic genes is kept in check by miR-6/11 to ensure normal development.

Figure Legend: : Embryonic phenotypes of miR-6/miR-11 double mutants

(A) Histogram showing percentage of embryos that completed embryonic development, assessed by hatching to first instar larval stage. Error bars represent standard deviation from 3 independent experiments. Student’s T test was used to assess the significance of the differences indicated. *= P<0.05.

(B) lateral views of embryos labeled by in situ hybridization to detect the primary transcript of miR-11 and miR-6 miRNAs. Scale bar: 50 µm.

(C) ventral views of embryos of the indicated genotypes labeled with antibody BP102. BP102 labels the axonal scaffold of the CNS. 11, 6R denotes the miR-11 mutant chromosome carrying the rescue transgene for miR-6. 11R denotes the RMCE rescued version of the miR-11 mutant. Scale bar: 50 µm.

(D) Higher magnification view to highlight the defects in the CNS. Scale bar: 50 µm. (E, F) Histograms showing quantification of the defects in the mutants and the rescued mutants.

(E) shows % of embryos affected in at least one segment of the CNS.

(F) shows the average number of affected segments per 10 segments scored. w1118 indicates the genotype of the control flies. Error bars represent standard deviation from at least 8 embryos. * indicates that the difference between the indicated pair was statistically significant p<0.05 (Student’s T test).

(G) ventral views of embryos of the indicated genotypes labeled with anti-Wrapper. Wrapper labels the midline glia of the CNS. Scale bar: 50 µm.

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