Massachusetts General Hospital, Department of Medicine, Nephrology Division, and Harvard Medical School Department of Genetics, Charlestown, Massachusetts.
Dev Dyn. 2013 Nov;242(11):1284-92. doi: 10.1002/dvdy.24026. Epub 2013 Sep 6.
odd-skipped related 2 (osr2) encodes a vertebrate ortholog of the Drosophila odd-skipped zinc-finger transcription factor. Osr2 in mouse is required for proper palate, eyelid, and bone development. Zebrafish knock-down experiments have also suggested a role for osr2, along with its paralog osr1, in early pectoral fin specification and pronephric development.
We show here that osr2 has a specific function later in development, independent of osr1, in the regulation of sox9a expression and promoting fin chondrogenesis. mRNA in situ hybridization demonstrated osr2 expression in the developing floorplate and later during organogenesis in the pronephros and gut epithelium. In the pectoral fin buds, osr2 was specifically expressed in fin mesenchyme. osr2 knock down in zebrafish embryos disrupted both three and five zinc finger alternatively spliced osr2 isoforms and eliminated wild-type osr2 mRNA. osr2 morphants exhibited normal pectoral fin bud specification but exhibited defective fin chondrogenesis, with loss of differentiated chondrocytes. Defects in chondrogenesis were paralleled by loss of sox9a as well as subsequent col2a1 expression, linking osr2 function to essential regulators of chondrogenesis.
The zebrafish odd-skipped related 2 gene regulates sox9a and col2a1 expression in chondrocyte development and is specifically required for zebrafish fin morphogenesis.
奇数跳跃相关 2（osr2）编码果蝇奇数跳跃锌指转录因子的脊椎动物同源物。小鼠中的 Osr2 对于腭、眼睑和骨骼的正常发育是必需的。斑马鱼的敲低实验也表明 osr2 及其旁系同源物 osr1 在早期胸鳍特化和前肾发育中具有作用。
我们在这里表明，osr2 在发育后期具有特定的功能，与 osr1 无关，在调节 sox9a 表达和促进鳍软骨发生中起作用。mRNA 原位杂交显示，osr2 在发育中的基板和随后的器官发生中在肾前体和肠上皮中表达。在胸鳍芽中，osr2 特异性地在鳍间充质中表达。斑马鱼胚胎中的 osr2 敲低破坏了三锌指和五锌指交替剪接的 osr2 异构体，并消除了野生型 osr2 mRNA。osr2 嵌合体表现出正常的胸鳍芽特化，但表现出鳍软骨发生缺陷，分化的软骨细胞缺失。软骨生成缺陷与 sox9a 的缺失以及随后的 col2a1 表达平行，将 osr2 功能与软骨生成的必需调节剂联系起来。
斑马鱼奇数跳跃相关 2 基因调节 sox9a 和 col2a1 在软骨细胞发育中的表达，并且是斑马鱼鳍形态发生所必需的。
