A zebrafish LMO4 ortholog limits the size of the forebrain and eyes through negative regulation of six3b and rx3
A zebrafish LMO4 ortholog limits the size of the forebrain and eyes through negative regulation of six3b and rx3
复制标题
DOI：
10.1016/j.ydbio.2007.07.004
复制
发表时间：
2007-09-15
影响因子：
2.7
通讯作者：
Lane, Mary Ellen
中科院分区：
文献类型：
--
作者：
McCollum, Catherine W.;Amin, Shivas R.;Lane, Mary Ellen
Six3和Rx3同源结构域蛋白对于脊椎动物脑的前脑和视网膜前体细胞的规范和增殖是必不可少的，并且控制其表达的调控网络开始被阐明。我们确定了斑马鱼lmo4b基因作为前脑生长的负调节因子，其作用是通过在早期分割阶段限制six3和rx3的表达。lmo4b的损失，吗啉敲低的结果扩大推定端脑和视泡和扩大后原肠胚表达域six3和rx3。通过mRNA注射过表达lmo4b导致互补的表型，包括前神经组织的量的减少，特别是在端脑，视神经和下丘脑原基，以及six3和rx3表达的剂量敏感性减少。我们建议，lmo4b活性是必需的，在神经边界，以限制six3b的表达，并在神经板内，以衰减rx3的表达独立于其对six3转录的影响。我们建议，lmo4b在前脑发育中具有重要作用，作为six3和rx3表达的调节剂，从而间接影响前中枢神经系统中的神经细胞命运承诺、细胞增殖和组织生长。爱思唯尔公司出版
The Six3 and Rx3 homeodomain proteins are essential for the specification and proliferation of forebrain and retinal precursor cells of the vertebrate brain, and the regulatory networks that control their expression are beginning to be elucidated. We identify the zebrafish lmo4b gene as a negative regulator of forebrain growth that acts via restriction of six3 and rx3 expression during early segmentation stages. Loss of lmo4b by morpholino knockdown results in enlargement of the presumptive telencephalon and optic vesicles and an expansion of the post-gastrula expression domains of six3 and rx3. Overexpression of lmo4b by mRNA injection causes complementary phenotypes, including a reduction in the amount of anterior neural tissue, especially in the telencephalic, optic and hypothalamic primordia, and a dosage-sensitive reduction in six3 and rx3 expression. We Suggest that lmo4b activity is required at the neural boundary to restrict six3b expression, and later within the neural plate to for attenuation of rx3 expression independently of its effect on six3 transcription. We propose that lmo4b has an essential role in forebrain development as a modulator of six3 and rx3 expression, and thus indirectly influences neural cell fate commitment, cell proliferation and tissue growth in the anterior CNS. Published by Elsevier Inc.