Regulation of Numb during planar cell polarity establishment in the Drosophila eye

IF 2.6 Q2 Medicine
Pedro M. Domingos, A. Jenny, David del Álamo, M. Mlodzik, H. Steller, B. Mollereau
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引用次数: 2

Abstract

The establishment of planar cell polarity (PCP) in the Drosophila eye requires correct specification of the R3/R4 pair of photoreceptor cells, determined by a Frizzled mediated signaling event that specifies R3 and induces Delta to activate Notch signaling in the neighboring cell, specifying it as R4. Here, we investigated the role of the Notch signaling negative regulator Numb in the specification of R3/R4 fates and PCP establishment in the Drosophila eye. We observed that Numb is transiently upregulated in R3 at the time of R3/R4 specification. This regulation of Numb levels in developing photoreceptors occurs at the post-transcriptional level and is dependent on Dishevelled, an effector of Frizzled signaling, and Lethal Giant Larva. We detected PCP defects in cells homozygous for numb15, but these defects were due to a loss of function mutation in fat (fatQ805*) being present in the numb15 chromosome. However, mosaic overexpression of Numb in R4 precursors (only) caused PCP defects and numb loss-of-function had a modifying effect on the defects found in a hypomorphic dishevelled mutation. Our results suggest that Numb levels are upregulated to reinforce the bias of Notch signaling activation in the R3/R4 pair, two post-mitotic cells that are not specified by asymmetric cell division.
Numb在果蝇眼睛平面细胞极性建立过程中的调节
果蝇眼睛中平面细胞极性(PCP)的建立需要正确指定R3/R4对光感受器细胞,由Frizzled介导的信号事件决定,该事件指定R3并诱导Delta激活相邻细胞中的Notch信号,将其指定为R4。在此,我们研究了Notch信号负调控子Numb在果蝇眼睛中R3/R4命运的规范和PCP的建立中的作用。我们观察到,在R3/R4规范时,Numb在R3中短暂上调。在发育中的光感受器中,麻木水平的调节发生在转录后水平,并依赖于disheveled(卷曲信号的效应物)和致命的巨型幼虫。我们在num15的纯合细胞中检测到PCP缺陷,但这些缺陷是由于在num15染色体中存在的脂肪(fatQ805*)的功能突变缺失。然而,在R4前体中嵌合过表达Numb(仅)引起PCP缺陷,而Numb的功能丧失对在次形凌乱突变中发现的缺陷具有修饰作用。我们的研究结果表明,Numb水平的上调加强了Notch信号激活在R3/R4对中的偏倚,这两个有丝分裂后的细胞不被不对称细胞分裂所指定。
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来源期刊
Mechanisms of Development
Mechanisms of Development 生物-发育生物学
CiteScore
3.60
自引率
0.00%
发文量
0
审稿时长
12.4 weeks
期刊介绍: Mechanisms of Development is an international journal covering the areas of cell biology and developmental biology. In addition to publishing work at the interphase of these two disciplines, we also publish work that is purely cell biology as well as classical developmental biology. Mechanisms of Development will consider papers in any area of cell biology or developmental biology, in any model system like animals and plants, using a variety of approaches, such as cellular, biomechanical, molecular, quantitative, computational and theoretical biology. Areas of particular interest include: Cell and tissue morphogenesis Cell adhesion and migration Cell shape and polarity Biomechanics Theoretical modelling of cell and developmental biology Quantitative biology Stem cell biology Cell differentiation Cell proliferation and cell death Evo-Devo Membrane traffic Metabolic regulation Organ and organoid development Regeneration Mechanisms of Development does not publish descriptive studies of gene expression patterns and molecular screens; for submission of such studies see Gene Expression Patterns.
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