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Abstract：
Transcriptional regulatory networks refine gene expression boundaries to define the dimensions of organ progenitor territories. Kidney progenitors originate within the intermediate mesoderm (IM), but the pathways that establish the boundary between the IM and neighboring vessel progenitors are poorly understood. Here, we delineate roles for the zinc-finger transcription factor Osr1 in kidney and vessel progenitor development. Zebrafish osr1 mutants display decreased IM formation and premature emergence of lateral vessel progenitors (LVPs). These phenotypes contrast with the increased IM and absent LVPs observed with loss of the bHLH transcription factor Hand2, and loss of hand2 partially suppresses osr1 mutant phenotypes. hand2 and osr1 are expressed together in the posterior mesoderm, but osr1 expression decreases dramatically prior to LVP emergence. Overexpressing osr1 during this timeframe inhibits LVP development while enhancing IM formation, and can rescue the osr1 mutant phenotype. Together, our data demonstrate that osr1 modulates the extent of IM formation and the temporal dynamics of LVP development, suggesting that a balance between levels of osr1 and hand2 expression is essential to demarcate the kidney and vessel progenitor territories.
摘要：
转录调控网络细化基因表达边界以定义器官祖细胞区域的维度。肾祖细胞起源于中间中胚层(IM)，但建立IM和邻近血管祖细胞之间边界的途径知之甚少。这里,我们描述了锌指转录因子Osr1在肾脏和血管祖细胞发育中的作用。斑马鱼osr1突变体显示出减少的IM形成和侧血管祖细胞（LVP）的过早出现。这些表型与bHLH转录因子Hand2丢失时观察到的IM增加和LVP缺失形成对比，而hand2的丢失部分抑制了osr1突变表型。hand2和osr1在后中胚层中一起表达，但osr1表达在LVP出现前显著下降。在此时间段内过度按压osr1抑制了LVP的发展，同时增强了IM的形成，并能挽救osr1突变表型。一起,我们的数据表明，osr1调节IM形成的程度和LVP发展的时间动态，表明osr1和hand2表达水平之间的平衡对于划分肾脏和血管祖细胞区域至关重要。
