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miR-190是果蝇神经系统中建立细胞极性和细胞分化的关键调节因子。

miR-190 is a Key Regulator in Establishing Cell Polarity and Specification in the Drosophila Nervous System.

作者信息

Ascencio Gerson, Galvan Laura, Sanchez Julie M, Nagainis Ariana, Tam Cynnie, Goins Lauren M, Riggs Blake

机构信息

Department of Biology, San Francisco State University, 1600 Holloway Ave., San Francisco, CA 94132.

Department of Developmental Biology, Stanford University, 279 Campus Dr., Stanford, CA 94305.

出版信息

bioRxiv. 2025 May 28:2025.05.28.656688. doi: 10.1101/2025.05.28.656688.

Abstract

Asymmetric cell division generates cellular diversity in developing tissues, particularly in the CNS. In neuroblasts, this process relies on polarity complexes and fate determinants, yet its molecular regulation remains unclear. Here, we identify miRNA-190 as a key regulator of neuroblast polarity and differentiation. Single-cell RNA sequencing and transcriptome analysis reveal that miR-190 deficiency disrupts CNS cell populations, reducing neurons while increasing neural progenitors and glia. Mechanistically, miR-190 is required for proper localization of the Par complex and basal determinants during mitosis. In miR-190 mutants, these factors mislocalize, leading to defective polarity and fate specification in embryonic neuroblast. qPCR analysis shows that miR-190 targets , which modulates Cdc42 activation and Par-6, crucial factors in neuroblast polarity. We propose a model in which miR-190 ensures proper Cdc42 activation and polarity establishment by targeting transcripts for degradation. miR-190 has been implicated in various cancers, and our findings provide a mechanistic framework for understanding miR-190's roles in tumorigenesis and its broader involvement in metabolic diseases.

摘要

不对称细胞分裂在发育中的组织,尤其是中枢神经系统中产生细胞多样性。在神经母细胞中,这一过程依赖于极性复合体和命运决定因子,但其分子调控机制仍不清楚。在这里,我们确定miRNA-190是神经母细胞极性和分化的关键调节因子。单细胞RNA测序和转录组分析表明,miR-190缺陷会破坏中枢神经系统细胞群体,减少神经元数量,同时增加神经祖细胞和神经胶质细胞。从机制上讲,miR-190是有丝分裂期间Par复合体和基底决定因子正确定位所必需的。在miR-190突变体中,这些因子定位错误,导致胚胎神经母细胞极性和命运特化出现缺陷。qPCR分析表明,miR-190靶向 ,后者调节Cdc42激活以及Par-6,而Par-6是神经母细胞极性中的关键因子。我们提出了一个模型,其中miR-190通过靶向转录本进行降解来确保Cdc42的正确激活和极性建立。miR-190与多种癌症有关,我们的研究结果为理解miR-190在肿瘤发生中的作用及其在代谢疾病中的更广泛参与提供了一个机制框架。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/525c/12154952/a38499d5bbad/nihpp-2025.05.28.656688v1-f0001.jpg

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