Zebrafish rx3 and mab21l2 are required during eye morphogenesis
Zebrafish rx3 and mab21l2 are required during eye morphogenesis
复制标题
DOI：
10.1016/j.ydbio.2004.02.026
复制
发表时间：
2004-06-15
影响因子：
2.7
通讯作者：
Brockerhoff, SE
中科院分区：
文献类型：
--
作者：
Kennedy, BN;Stearns, GW;Brockerhoff, SE
在正在进行的斑马鱼F-3突变筛选中，发现了盲目突变体chokh(Chk)的两个等位基因。在形态上，由于视神经原基不能从前脑外翻，在受精后15it就可以发现chk突变体。Chk表型似乎是特定的，因为在前脑、中脑和松果体中的标记基因以正常的时间、空间和昼夜模式表达。对chk等位基因的序列分析显示，rx3同源框存在无义或错义突变。RX基因编码成对类型的同源结构域转录因子，已知在小鼠、青竹、非洲爪哇和斑马鱼中是眼睛发育的关键调节因子。为了发现新的Rx靶点，我们分析了多个眼睛发育基因在CHK中的表达。我们发现mab21l2、mab21l1和RX2在CHK胚胎的眼野中不表达。通过反义吗啉微量注射抑制Mab21l2，部分复制了rx3突变，导致小眼球，眼部不完全成熟，以及眼祖细胞凋亡的急剧增加。我们认为mab21l2是rx3的早期下游效应因子，对眼祖细胞的存活至关重要。(C)2004 Elsevier Inc.保留所有权利。
Two alleles of an eyeless mutant, chokh (chk), were identified in ongoing zebrafish F-3 mutagenesis screens. Morphologically, chk mutants can be identified at 15 It post-fertilization by the failure of optic primordia to evaginate from the forebrain. The chk phenotype appears specific, as marker genes in the forebrain, midbrain, and pineal are expressed in normal temporal, spatial, and circadian patterns. Sequence analysis of the chk alleles revealed nonsense or missense mutations in the rx3 homeobox. Rx genes encode paired-type homeodomain transcription factors known to be key regulators of eye development in mouse, medaka, Xenopus, and zebrafish. To uncover novel Rx targets, we analyzed the expression of multiple eye development genes in chk. We find that expression of mab21l2, mab21l1 and rx2 are specifically absent in the eye field of chk embryos. Knockdown of Mab21l2 by antisense morpholino microinjections partially phenocopies the rx3 mutation, leading to microphthalmia, incomplete eye maturation, and dramatic increases in apoptotic eye progenitors. We propose that mab21l2 is an early downstream effector of rx3 and is critical for survival of eye progenitors. (C) 2004 Elsevier Inc. All rights reserved.