Department of Developmental Biology, Sloan-Kettering Institute, 1275 York Avenue, Box 252, New York, NY 10065, USA; Centro de Biología Molecular Severo Ochoa (C.S.I.C.-U.A.M.), Universidad Autónoma de Madrid, Nicolás Cabrera 1, Cantoblanco, 28049 Madrid, Spain.
2401 Life Sciences Centre, 2350 Health Sciences Mall, University of British Columbia, Vancouver, BC V6T 1Z3, Canada.
Dev Cell. 2014 Jun 23;29(6):635-48. doi: 10.1016/j.devcel.2014.04.023. Epub 2014 Jun 5.
The Drosophila Bithorax complex (BX-C) Hox cluster contains a bidirectionally transcribed miRNA locus, and a deletion mutant (Δmir) lays no eggs and is completely sterile. We show these miRNAs are expressed and active in distinct spatial registers along the anterior-posterior axis in the CNS. Δmir larvae derepress a network of direct homeobox gene targets in the posterior ventral nerve cord (VNC), including BX-C genes and their TALE cofactors. These are phenotypically critical targets, because sterility of Δmir mutants was substantially rescued by heterozygosity of these genes. The posterior VNC contains Ilp7+ oviduct motoneurons, whose innervation and morphology are defective in Δmir females, and substantially rescued by heterozygosity of Δmir targets, especially within the BX-C. Collectively, we reveal (1) critical roles for Hox miRNAs that determine segment-specific expression of homeotic genes, which are not masked by transcriptional regulation; and (2) that BX-C miRNAs are essential for neural patterning and reproductive behavior.
果蝇 Bithorax 复合体 (BX-C) Hox 簇包含一个双向转录的 miRNA 基因座，缺失突变体 (Δmir) 不能产卵，完全不育。我们发现这些 miRNA 在 CNS 沿前后轴的不同空间区域表达并具有活性。Δmir 幼虫在后腹神经索 (VNC) 中解除了一组直接同源盒基因靶标的抑制，包括 BX-C 基因及其 TALE 共因子。这些是表型上至关重要的靶标，因为这些基因的杂合性可以显著挽救 Δmir 突变体的不育性。后 VNC 包含 Ilp7+ 输卵管运动神经元，其在 Δmir 雌性中的神经支配和形态存在缺陷，而 Δmir 靶基因的杂合性可以显著挽救，特别是在 BX-C 中。总的来说，我们揭示了 (1) Hox miRNA 在确定同源盒基因的特定节段表达中的关键作用，这些作用不受转录调控的掩盖；以及 (2) BX-C miRNA 对神经模式形成和生殖行为是必不可少的。
