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SEM-2/SoxC调节胚胎后中胚层发育的多个方面。

SEM-2/SoxC regulates multiple aspects of postembryonic mesoderm development.

作者信息

Baccas Marissa, Ganesan Vanathi, Leung Amy, Pineiro Lucas, McKillop Alexandra N, Liu Jun

机构信息

Department of Molecular Biology and Genetics, Cornell University, Ithaca, NY 14853.

出版信息

bioRxiv. 2024 Jul 4:2024.07.04.602042. doi: 10.1101/2024.07.04.602042.

DOI:10.1101/2024.07.04.602042
PMID:39005444
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11245110/
Abstract

Development of multicellular organisms requires well-orchestrated interplay between cell-intrinsic transcription factors and cell-cell signaling. One set of highly conserved transcription factors that plays diverse roles in development is the SoxC group. contains a sole SoxC protein, SEM-2. SEM-2 is essential for embryonic development, and for specifying the sex myoblast (SM) fate in the postembryonic mesoderm, the M lineage. We have identified a novel partial loss-of-function allele that has a proline to serine change in the C-terminal tail of the highly conserved DNA-binding domain. Detailed analyses of mutant animals harboring this point mutation uncovered new functions of SEM-2 in the M lineage. First, SEM-2 functions antagonistically with LET-381, the sole FoxF/C forkhead transcription factor, to regulate dorsoventral patterning of the M lineage. Second, in addition to specifying the SM fate, SEM-2 is essential for the proliferation and diversification of the SM lineage. Finally, SEM-2 appears to directly regulate the expression of , which encodes a basic helix-loop-helix Twist transcription factor and plays critical roles in proper patterning of the M lineage. Our data, along with previous studies, suggest an evolutionarily conserved relationship between SoxC and Twist proteins. Furthermore, our work identified new interactions in the gene regulatory network (GRN) underlying postembryonic development and adds to the general understanding of the structure-function relationship of SoxC proteins.

摘要

多细胞生物的发育需要细胞内在转录因子与细胞间信号传导之间精心协调的相互作用。在发育过程中发挥多种作用的一组高度保守的转录因子是SoxC家族。[该生物]仅含有一种SoxC蛋白,即SEM-2。SEM-2对胚胎发育至关重要,并且对于确定胚胎后中胚层(M谱系)中性肌母细胞(SM)的命运也很关键。我们鉴定出了一个新的功能部分丧失的等位基因,该等位基因在高度保守的DNA结合结构域的C末端尾巴中有一个脯氨酸到丝氨酸的变化。对携带此点突变的突变动物的详细分析揭示了SEM-2在M谱系中的新功能。首先,SEM-2与唯一的FoxF/C叉头转录因子LET-381发挥拮抗作用,以调节M谱系的背腹模式形成。其次,除了确定SM命运外,SEM-2对于SM谱系的增殖和多样化也至关重要。最后,SEM-2似乎直接调节[某基因]的表达,该基因编码一种基本的螺旋-环-螺旋Twist转录因子,并在M谱系的正确模式形成中发挥关键作用。我们的数据以及先前的研究表明,SoxC和Twist蛋白之间存在进化上保守的关系。此外,我们的工作确定了胚胎后发育基础基因调控网络(GRN)中的新相互作用,并增进了对SoxC蛋白结构-功能关系的总体理解。

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本文引用的文献

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A Twist-Box domain of the C. elegans Twist homolog, HLH-8, plays a complex role in transcriptional regulation.线虫 Twist 同源物 HLH-8 的 Twist-Box 结构域在转录调控中发挥复杂作用。
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The Caenorhabditis elegans ASPP homolog APE-1 is a junctional protein phosphatase 1 modulator.秀丽隐杆线虫 ASPP 同源物 APE-1 是一种连接蛋白磷酸酶 1 调节剂。
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A 4D single-cell protein atlas of transcription factors delineates spatiotemporal patterning during embryogenesis.一个 4D 单细胞转录因子蛋白质图谱描绘了胚胎发生过程中的时空模式。
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Positive autoregulation of in response to LIN-12 activation in cell fate decisions during reproductive system development.在生殖系统发育过程中,细胞命运决定中 LIN-12 激活引发 的正反馈自调节。
Development. 2020 Sep 28;147(18):dev193482. doi: 10.1242/dev.193482.
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SOX4: The unappreciated oncogene.SOX4:未被充分认识的致癌基因。
Semin Cancer Biol. 2020 Dec;67(Pt 1):57-64. doi: 10.1016/j.semcancer.2019.08.027. Epub 2019 Aug 21.
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SOXopathies: Growing Family of Developmental Disorders Due to SOX Mutations.SOX 相关病变:由于 SOX 基因突变导致的不断增加的发育障碍疾病家族。
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