Iroquois transcription factor irx2a is required for multiciliated and transporter cell fate decisions during zebrafish pronephros development.
Iroquois transcription factor irx2a is required for multiciliated and transporter cell fate decisions during zebrafish pronephros development.
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易洛魁转录因子 irx2a 是斑马鱼前肾发育过程中多纤毛细胞和转运细胞命运决定所必需的。
DOI：
10.1038/s41598-019-42943-y
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发表时间：
2019
影响因子：
4.6
通讯作者：
Wingert,RebeccaA
中科院分区：
文献类型：
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作者：
Marra,AmandaN;Cheng,ChristinaN;Adeeb,Basma;Addiego,Amanda;Wesselman,HannahM;Chambers,BrookeE;Chambers,JosephM;Wingert,RebeccaA
肾脏器官发生过程中肾元模式的遗传调控仍然知之甚少。斑马鱼的肾小管由具有独特吸收和分泌作用的段群以及控制流体流动的多纤毛细胞（mcc）组成。在这里，我们报道转录因子irx2a是斑马鱼肾形成所必需的。irx2转录子定位于发育中的原肾细胞和成熟的MCC，功能缺失改变了两个片段群体的形成，减少了MCC的数量。有趣的是，irx2a缺陷的胚胎减少了MCC基本基因变体5a （etv5a）的表达，并通过yetv5a的过表达而被拯救，这支持了etv5在firx2的下游作用以控制MCC发生的结论。最后，我们发现维甲酸（RA）信号通路影响它们在肾祖细胞中的x2a表达域，定位在RA的下游。总之，这项工作揭示了irx2在肾发生过程中的新作用，确定了irx2在RA信号传导、分割和控制fetv5介导的MCC形成之间的关键联系。对这些事件中涉及的遗传因素的进一步研究将增强我们对控制肾脏发育的分子途径的理解，这可以用来帮助创造治疗先天性和获得性肾脏疾病的疗法。
The genetic regulation of nephron patterning during kidney organogenesis remains poorly understood. Nephron tubules in zebrafish are composed of segment populations that have unique absorptive and secretory roles, as well as multiciliated cells (MCCs) that govern fluid flow. Here, we report that the transcription factoriroquois 2a(irx2a) is requisite for zebrafish nephrogenesis.irx2atranscripts localized to the developing pronephros and maturing MCCs, and loss of function altered formation of two segment populations and reduced MCC number. Interestingly,irx2adeficient embryos had reduced expression of an essential MCC geneets variant 5a (etv5a), and were rescued byetv5aoverexpression, supporting the conclusion thatetv5aacts downstream ofirx2ato control MCC ontogeny. Finally, we found that retinoic acid (RA) signaling affects theirx2aexpression domain in renal progenitors, positioningirx2adownstream of RA. In sum, this work reveals new roles forirx2aduring nephrogenesis, identifyingirx2aas a crucial connection between RA signaling, segmentation, and the control ofetv5amediated MCC formation. Further investigation of the genetic players involved in these events will enhance our understanding of the molecular pathways that govern renal development, which can be used help create therapeutics to treat congenital and acquired kidney diseases.