The lineage-specific gene ponzr1 is essential for zebrafish pronephric and pharyngeal arch development

The lineage-specific gene ponzr1 is essential for zebrafish pronephric and pharyngeal arch development
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DOI:
10.1242/dev.071720
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发表时间:
2012-02-15
期刊:
影响因子:
4.6
通讯作者:
Ekker, Stephen C.
Ekker, Stephen C.
中科院分区:
生物学2区
文献类型:
--
作者:
Bedell, Victoria M.;Person, Anthony D.;Ekker, Stephen C.

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同源异型盒(Homeobox,Hox)和配对盒(Paired box,Pax)基因家族是决定动物体型和器官结构的关键基因。特别是,它们在控制器官发生的调控网络中发挥作用。这些保守的基因是如何在进化压力下引起器官形态和功能的差异的,还没有完全弄清楚。我们的分子和功能特征的一个成员的进化动态基因家族,plac8 onzin相关蛋白1(ponzr1),在斑马鱼。PONZR 1 mRNA在发育中的肾脏和咽弓中早期表达。使用ponzr1靶向吗啉,我们表明,ponzr1是必要的肾小球的形成。ponzr1的缺失导致肾小球无功能,但保留功能性原肾,这种排列类似于在海洋鱼类亚群中发现的无肾小球肾。PONZR 1被整合到PAX2A途径中,PONZR 1的表达需要PAX2A基因的功能,而PAX2A的正常表达需要PONZR 1的正常表达。除了前肾功能外,ponzr1还需要咽弓的形成。我们在功能上证明了ponzr1可以作为一个转录因子或辅助因子,为这个新描述的基因家族提供了第一个分子作用模式。总之,这项工作提供了一个额外的机制,将进化动态,谱系特异性基因家族到保守的调控基因网络,创造功能器官的多样性的实验证据。
The Homeobox (Hox) and Paired box (Pax) gene families are key determinants of animal body plans and organ structure. In particular, they function within regulatory networks that control organogenesis. How these conserved genes elicit differences in organ form and function in response to evolutionary pressures is incompletely understood. We molecularly and functionally characterized one member of an evolutionarily dynamic gene family, plac8 onzin related protein 1 (ponzr1), in the zebrafish. ponzr1 mRNA is expressed early in the developing kidney and pharyngeal arches. Using ponzr1-targeting morpholinos, we show that ponzr1 is required for formation of the glomerulus. Loss of ponzr1 results in a nonfunctional glomerulus but retention of a functional pronephros, an arrangement similar to the aglomerular kidneys found in a subset of marine fish. ponzr1 is integrated into the pax2a pathway, with ponzr1 expression requiring pax2a gene function, and proper pax2a expression requiring normal ponzr1 expression. In addition to pronephric function, ponzr1 is required for pharyngeal arch formation. We functionally demonstrate that ponzr1 can act as a transcription factor or co-factor, providing the first molecular mode of action for this newly described gene family. Together, this work provides experimental evidence of an additional mechanism that incorporates evolutionarily dynamic, lineage-specific gene families into conserved regulatory gene networks to create functional organ diversity.