INDUCTIVE INTERACTIONS DURING EARLY EYE DEVELOPMENT

早期眼睛发育过程中的感应互动

基本信息

批准号：
2164803
负责人：
Olof H Sundin
金额：
$ 17.42万
依托单位：
JOHNS HOPKINS UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
1994
资助国家：
美国
起止时间：
1994-09-01 至 1998-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/2164803
关键词：
DNA binding protein biological signal transduction cell cell interaction cell communication molecule cell differentiation chick embryo developmental genetics developmental neurobiology ectoderm embryogenesis eye gene expression genetic markers in situ hybridization mesoderm neural plate /tube nonmammalian vertebrate embryology tissue /cell culture

项目摘要

Cells committed to formation of the eye arise within the anterior neural plate during early development of the brain. It is our long term coal to understand the molecular basis of their origin and later development into ocular tissues. Such understanding would be of relevance to the- diagnosis and possible prevention of many defects in eye development that are of genetic or environmental origin. In addition, this knowledge could ultimately lead to methods for the in vitro culture of human retinal stem cells, and the use of such stem cells in efforts to restore vision by cell transplantation. The scope of this proposal is to identify inductive interactions that regulate cell fate during the establishment of the eye. We will carry out surgical manipulations on the early chick embryo to infer the presence of such interactions between tissues. The use of wholemount in situ hybridization to detect specific messenger RNAs will allow us to directly visualize the changes in gene expression that precede and accompany the formation of ocular structures in the embryo. One such molecular marker, the Pax-6 gene, is a highly conserved regulator of transcription that is essential to eye development. It is associated with aniridia, a human genetic disorder affecting formation of the eye. In the early embryo, Pax-6 is expressed at high levels in the optic vesicle and early lens placode, as well as the neural and ectodermal primordia which give rise to these structures. Another marker, which we have recently isolated and designated lOA6, is a gene expressed almost exclusively within the early optic cup and retina. Specifically, we will first determine whether certain regions of mesoderm in the chick gastrula are required for the establishment of a single, cyclopic eye forming region. We will then determine whether mesoderm underlying the emerging neural plate shapes this eye forming region into two separate primordia. The establishment of clear assays for such interactions provides a basis for future experiments designed to approach their molecular nature. At another crucial stage, the early forebrain has developed two outgrowths known as optic vesicles. We will determine whether the overlying head ectoderm, which is fated to become the lens, provides signals essential to the growth and formation of these vesicles into optic cups. The optic cup represents a key step in the spatial organization and establishment of the retina, iris, ciliary body and pigment epithelium. Finally, we will investigate the possibility that cell cultures undergoing lens differentiation can provide a source of inductive factors which act upon the optic vesicle. This would make possible the biochemical study and eventual identification of such signalling molecules.

致力于形成眼睛的细胞发生在前神经内板在大脑早期发育过程中。这是我们的长期煤炭了解其起源的分子基础和后来的发展进入眼组织。这样的理解将与 - 诊断和可能预防眼睛发育中的许多缺陷具有遗传或环境起源。此外，这些知识最终可能导致人类体外培养的方法视网膜干细胞，并使用此类干细胞恢复通过细胞移植视力。该提案的范围是确定归纳互动在建立眼睛期间调节细胞命运。我们会随身携带在早期的小鸡胚胎上进行手术操作，以推断组织之间存在这种相互作用。在检测特定Messenger RNA的原位杂交将使我们能够直接可视化和之前的基因表达变化伴随胚胎中的眼睛结构的形成。一个这样的分子标记物，PAX-6基因，是高度保守的调节剂对眼睛发育至关重要的转录。它是关联的与阿尼里亚（Aniridia）一起，一种影响眼睛形成的人类遗传疾病。在早期的胚胎中，PAX-6在光学上以高水平表示囊泡和早期镜头片段，以及神经和外胚层产生这些结构的原始。另一个标记，我们最近已经隔离并指定了loa6，是一个几乎表达的基因仅在早期的视频杯和视网膜内。具体来说，我们将首先确定某些地区是否鸡胃中的中胚层建立了单个环形眼睛形成区域。然后，我们将确定是否中胚层为新兴的神经板形塑造这种眼睛形成区域分为两个独立的原始。建立清晰的测定对于此类互动，为将来设计的实验提供了基础接近他们的分子本质。在另一个关键阶段，早期前脑开发了两个称为光囊泡的产物。我们将确定上覆的头外胚层，即将变为镜头提供了对生长和形成至关重要的信号这些囊泡变成光杯。光学杯代表着关键的步骤视网膜，虹膜，睫状的空间组织和建立身体和色素上皮。最后，我们将调查经历晶状体分化的细胞培养物可能提供对视囊作用的电感因子的来源。这将使生化研究和最终鉴定这种信号分子。

项目成果

期刊论文数量（3）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

The optx2 homeobox gene is expressed in early precursors of the eye and activates retina-specific genes.

optx2 同源盒基因在眼睛的早期前体中表达并激活视网膜特异性基因。

DOI：
10.1073/pnas.95.18.10643
发表时间：
1998
期刊：
Proceedings of the National Academy of Sciences of the United States of America
影响因子：
11.1
作者：
Toy,J;Yang,JM;Leppert,GS;Sundin,OH
通讯作者：
Sundin,OH

Sequence and location of SIX3, a homeobox gene expressed in the human eye.