Sander Veronika, Reversade Bruno, De Robertis E M
Howard Hughes Medical Institute and Department of Biological Chemistry, University of California-Los Angeles, 675 Charles Young Drive South, Los Angeles, CA 90095, USA.
EMBO J. 2007 Jun 20;26(12):2955-65. doi: 10.1038/sj.emboj.7601705. Epub 2007 May 24.
We present a loss-of-function study using antisense morpholino (MO) reagents for the organizer-specific gene Goosecoid (Gsc) and the ventral genes Vent1 and Vent2. Unlike in the mouse Gsc is required in Xenopus for mesodermal patterning during gastrulation, causing phenotypes ranging from reduction of head structures-including cyclopia and holoprosencephaly-to expansion of ventral tissues in MO-injected embryos. The overexpression effects of Gsc mRNA require the expression of the BMP antagonist Chordin, a downstream target of Gsc. Combined Vent1 and Vent2 MOs strongly dorsalized the embryo. Unexpectedly, simultaneous depletion of all three genes led to a rescue of almost normal development in a variety of embryological assays. Thus, the phenotypic effects of depleting Gsc or Vent1/2 are caused by the transcriptional upregulation of their opposing counterparts. A principal function of Gsc and Vent1/2 homeobox genes might be to mediate a self-adjusting mechanism that restores the basic body plan when deviations from the norm occur, rather than generating individual cell types. The results may shed light on the molecular mechanisms of genetic redundancy.
我们利用针对组织者特异性基因Goosecoid(Gsc)以及腹侧基因Vent1和Vent2的反义吗啉代寡核苷酸(MO)试剂进行了一项功能丧失研究。与在小鼠中不同,在非洲爪蟾中,原肠胚形成期间中胚层模式的形成需要Gsc,这会导致MO注射胚胎出现从头部结构减少(包括独眼畸形和前脑无裂畸形)到腹侧组织扩张等一系列表型。Gsc mRNA的过表达效应需要BMP拮抗剂Chordin(Gsc的下游靶点)的表达。Vent1和Vent2 MOs联合使用会使胚胎强烈背化。出乎意料的是,在各种胚胎学检测中,同时敲除这三个基因会导致胚胎几乎恢复正常发育。因此,敲除Gsc或Vent1/2所产生的表型效应是由其相对应基因的转录上调引起的。Gsc和Vent1/2同源框基因的一个主要功能可能是介导一种自我调节机制,当出现与正常情况的偏差时恢复基本的身体结构,而不是产生单个细胞类型。这些结果可能有助于揭示基因冗余的分子机制。