Rbm8a缺乏通过调节Wnt/PCP信号导致造血缺陷。

IF 2.1 3区 生物学 Q2 DEVELOPMENTAL BIOLOGY
Agnese Kocere , Elena Chiavacci , Charlotte Soneson , Seth T. Jacobson , Emma N. Harrison , Kevin Manuel Méndez-Acevedo , Jacalyn S. MacGowan , Harrison H. Wells , Max S. Hiltabidle , Azhwar Raghunath , Jordan A. Shavit , Daniela Panáková , Margot L.K. Williams , Mark D. Robinson , Christian Mosimann , Alexa Burger
{"title":"Rbm8a缺乏通过调节Wnt/PCP信号导致造血缺陷。","authors":"Agnese Kocere ,&nbsp;Elena Chiavacci ,&nbsp;Charlotte Soneson ,&nbsp;Seth T. Jacobson ,&nbsp;Emma N. Harrison ,&nbsp;Kevin Manuel Méndez-Acevedo ,&nbsp;Jacalyn S. MacGowan ,&nbsp;Harrison H. Wells ,&nbsp;Max S. Hiltabidle ,&nbsp;Azhwar Raghunath ,&nbsp;Jordan A. Shavit ,&nbsp;Daniela Panáková ,&nbsp;Margot L.K. Williams ,&nbsp;Mark D. Robinson ,&nbsp;Christian Mosimann ,&nbsp;Alexa Burger","doi":"10.1016/j.ydbio.2025.08.021","DOIUrl":null,"url":null,"abstract":"<div><div>Thrombocytopenia-Absent Radius (TAR) syndrome is a rare congenital condition with reduced platelets, forelimb anomalies, and variable heart and kidney defects. TAR syndrome is caused by mutations in <em>RBM8A/Y14</em>, a component of the exon junction complex. How perturbing a general mRNA-processing factor causes the selective TAR Syndrome phenotypes remains unknown. Here, we connect zebrafish <em>rbm8a</em> perturbation to early hematopoietic defects via attenuated non-canonical Wnt/Planar Cell Polarity (PCP) signaling. In hypomorphic <em>rbm8a</em> zebrafish, we observe a reduction of <em>cd41</em>-positive thrombocytes. <em>rbm8a</em>-mutant zebrafish accumulate mRNAs with retained introns, including non-canonical Wnt/PCP pathway components resulting in convergent extension defects. We found that reduced <em>rbm8a</em> function interacts with perturbations in non-canonical Wnt/PCP pathway genes w<em>nt5b</em>, <em>wnt11f2</em>, <em>fzd7a</em>, and <em>vangl2</em>, impairing the architecture of the lateral plate mesoderm (LPM) that forms hematopoietic, cardiovascular, kidney, and forelimb skeleton progenitors. Both mutants for <em>rbm8a</em> and for the PCP gene <em>vangl2</em> feature impaired expression of early hematopoietic/endothelial genes <em>runx1</em> and <em>gfi1aa</em>. Together, our data propose aberrant LPM patterning and hematopoietic defects as consequence of attenuated non-canonical Wnt/PCP signaling upon reduced <em>rbm8a</em> function.</div></div>","PeriodicalId":11070,"journal":{"name":"Developmental biology","volume":"528 ","pages":"Pages 34-56"},"PeriodicalIF":2.1000,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Rbm8a deficiency causes hematopoietic defects by modulating Wnt/PCP signaling\",\"authors\":\"Agnese Kocere ,&nbsp;Elena Chiavacci ,&nbsp;Charlotte Soneson ,&nbsp;Seth T. Jacobson ,&nbsp;Emma N. Harrison ,&nbsp;Kevin Manuel Méndez-Acevedo ,&nbsp;Jacalyn S. MacGowan ,&nbsp;Harrison H. Wells ,&nbsp;Max S. Hiltabidle ,&nbsp;Azhwar Raghunath ,&nbsp;Jordan A. Shavit ,&nbsp;Daniela Panáková ,&nbsp;Margot L.K. Williams ,&nbsp;Mark D. Robinson ,&nbsp;Christian Mosimann ,&nbsp;Alexa Burger\",\"doi\":\"10.1016/j.ydbio.2025.08.021\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><div>Thrombocytopenia-Absent Radius (TAR) syndrome is a rare congenital condition with reduced platelets, forelimb anomalies, and variable heart and kidney defects. TAR syndrome is caused by mutations in <em>RBM8A/Y14</em>, a component of the exon junction complex. How perturbing a general mRNA-processing factor causes the selective TAR Syndrome phenotypes remains unknown. Here, we connect zebrafish <em>rbm8a</em> perturbation to early hematopoietic defects via attenuated non-canonical Wnt/Planar Cell Polarity (PCP) signaling. In hypomorphic <em>rbm8a</em> zebrafish, we observe a reduction of <em>cd41</em>-positive thrombocytes. <em>rbm8a</em>-mutant zebrafish accumulate mRNAs with retained introns, including non-canonical Wnt/PCP pathway components resulting in convergent extension defects. We found that reduced <em>rbm8a</em> function interacts with perturbations in non-canonical Wnt/PCP pathway genes w<em>nt5b</em>, <em>wnt11f2</em>, <em>fzd7a</em>, and <em>vangl2</em>, impairing the architecture of the lateral plate mesoderm (LPM) that forms hematopoietic, cardiovascular, kidney, and forelimb skeleton progenitors. Both mutants for <em>rbm8a</em> and for the PCP gene <em>vangl2</em> feature impaired expression of early hematopoietic/endothelial genes <em>runx1</em> and <em>gfi1aa</em>. Together, our data propose aberrant LPM patterning and hematopoietic defects as consequence of attenuated non-canonical Wnt/PCP signaling upon reduced <em>rbm8a</em> function.</div></div>\",\"PeriodicalId\":11070,\"journal\":{\"name\":\"Developmental biology\",\"volume\":\"528 \",\"pages\":\"Pages 34-56\"},\"PeriodicalIF\":2.1000,\"publicationDate\":\"2025-09-02\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Developmental biology\",\"FirstCategoryId\":\"99\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S0012160625002386\",\"RegionNum\":3,\"RegionCategory\":\"生物学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"DEVELOPMENTAL BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Developmental biology","FirstCategoryId":"99","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0012160625002386","RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"DEVELOPMENTAL BIOLOGY","Score":null,"Total":0}
引用次数: 0

摘要

血小板减少-桡骨缺失综合征(TAR)是一种罕见的先天性疾病,伴有血小板减少、前肢异常以及可变的心脏和肾脏缺陷。TAR综合征是由RBM8A/Y14突变引起的,RBM8A/Y14是外显子连接复合体的一个组成部分。干扰一般mrna加工因子如何导致选择性TAR综合征表型仍然未知。在这里,我们通过减弱的非规范Wnt/平面细胞极性(PCP)信号将斑马鱼rbm8a扰动与早期造血缺陷联系起来。在半胚rbm8a斑马鱼中,我们观察到cd41阳性血小板减少。rbm8a突变斑马鱼积累带有保留内含子的mrna,包括非规范的Wnt/PCP途径成分,导致趋同扩展缺陷。我们发现rbm8a功能的降低与非典型Wnt/PCP通路基因wnt5b、wnt11f2、fzd7a和vangl2的扰动相互作用,损害形成造血、心血管、肾脏和前肢骨骼祖细胞的侧板中胚层(LPM)的结构。rbm8a和PCP基因vangl2的两个突变体都表现出早期造血/内皮基因runx1和gfi1aa的表达受损。总之,我们的数据表明,rbm8a功能降低后,非规范Wnt/PCP信号减弱,导致LPM模式异常和造血缺陷。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Rbm8a deficiency causes hematopoietic defects by modulating Wnt/PCP signaling

Rbm8a deficiency causes hematopoietic defects by modulating Wnt/PCP signaling
Thrombocytopenia-Absent Radius (TAR) syndrome is a rare congenital condition with reduced platelets, forelimb anomalies, and variable heart and kidney defects. TAR syndrome is caused by mutations in RBM8A/Y14, a component of the exon junction complex. How perturbing a general mRNA-processing factor causes the selective TAR Syndrome phenotypes remains unknown. Here, we connect zebrafish rbm8a perturbation to early hematopoietic defects via attenuated non-canonical Wnt/Planar Cell Polarity (PCP) signaling. In hypomorphic rbm8a zebrafish, we observe a reduction of cd41-positive thrombocytes. rbm8a-mutant zebrafish accumulate mRNAs with retained introns, including non-canonical Wnt/PCP pathway components resulting in convergent extension defects. We found that reduced rbm8a function interacts with perturbations in non-canonical Wnt/PCP pathway genes wnt5b, wnt11f2, fzd7a, and vangl2, impairing the architecture of the lateral plate mesoderm (LPM) that forms hematopoietic, cardiovascular, kidney, and forelimb skeleton progenitors. Both mutants for rbm8a and for the PCP gene vangl2 feature impaired expression of early hematopoietic/endothelial genes runx1 and gfi1aa. Together, our data propose aberrant LPM patterning and hematopoietic defects as consequence of attenuated non-canonical Wnt/PCP signaling upon reduced rbm8a function.
求助全文
通过发布文献求助,成功后即可免费获取论文全文。 去求助
来源期刊
Developmental biology
Developmental biology 生物-发育生物学
CiteScore
5.30
自引率
3.70%
发文量
182
审稿时长
1.5 months
期刊介绍: Developmental Biology (DB) publishes original research on mechanisms of development, differentiation, and growth in animals and plants at the molecular, cellular, genetic and evolutionary levels. Areas of particular emphasis include transcriptional control mechanisms, embryonic patterning, cell-cell interactions, growth factors and signal transduction, and regulatory hierarchies in developing plants and animals.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:604180095
Book学术官方微信