Molecular and Cellular Biology Institute (IBR), National Council of Scientific and Technological Research (CONICET)-Biology Area, Department of Biological Sciences, Faculty of Biochemical and Pharmaceutical Sciences, National University of Rosario, Suipacha 531, Rosario, S2002LRK, Argentina.
Dev Growth Differ. 2011 Oct;53(8):934-47. doi: 10.1111/j.1440-169X.2011.01298.x.
Cellular nucleic acid binding protein (Cnbp) is a highly conserved single-stranded nucleic acid binding protein required for rostral head development. The use of a morpholino that inhibits Cnbp mRNA translation previously revealed a role of Cnbp in balancing neural crest cell apoptosis and proliferation in the developing zebrafish. Here, we report the use of another morpholino that specifically modifies the splicing of Cnbp pre-mRNA resulting in a reduction of full-length mRNA levels along with the generation of a novel transcript coding for an isoform that may act as dominant negative proteins. The use of this morpholino resulted in more severe phenotypes that enabled us to demonstrate that Cnbp loss-of-function adversely affects the formation and survival of craniofacial cartilaginous structures not only controlling the ratio of cell proliferation and apoptosis but also defining skeletogenic neural crest cell fate.
细胞核酸结合蛋白(Cnbp)是一种高度保守的单链核酸结合蛋白,对于头端的发育是必需的。使用一种抑制 Cnbp mRNA 翻译的反义寡核苷酸,先前揭示了 Cnbp 在平衡斑马鱼发育过程中神经嵴细胞凋亡和增殖中的作用。在这里,我们报告使用另一种反义寡核苷酸,其特异性修饰 Cnbp 前体 mRNA 的剪接,导致全长 mRNA 水平降低,同时产生一种新的转录本,编码一种可能作为显性负性蛋白的同工型。使用这种反义寡核苷酸导致更严重的表型,使我们能够证明 Cnbp 功能丧失会不利地影响颅面软骨结构的形成和存活,不仅控制细胞增殖和凋亡的比例,而且定义成骨神经嵴细胞命运。