Studies of Animal Development by Identification of Transcriptional Target Genes

我们已经免疫纯化了小鼠mAb-21基因Mab 2111作为HOXC 4的靶候选物。mAb-21基因首先在秀丽隐杆线虫中被鉴定，因为它需要射线身份鉴定。目前已知，它构成了一个从脊椎动物到无脊椎动物高度保守的基因家族，并且在许多物种中已经鉴定出两个同源物，Mab 2111和Mab 2112。我们描述了一代Mab 2111缺陷小鼠的眼睛和包皮腺形成的缺陷。突变小鼠眼睛具有由增殖缺陷引起的透镜基板内陷不充分导致的退化的透镜。嵌合体的分析表明，透镜基板的影响，在一个细胞自主的方式，虽然Mab 2111在透镜基板和视泡中表达。透镜基板发育的缺陷与Foxe 3的延迟和不足表达相关，Foxe 3也是透镜发育所需的，而Maf、Sox 2、Six 3和PAX 6水平不受显著影响。Mab 2111在Sey纯合子的视泡和上覆表面外胚层中的表达显著减少，表明Mab 2111在发育中的眼睛中的表达依赖于Pax 6基因产物的功能。我们的结论是Mab 2111的表达依赖于PAX 6是必不可少的透镜基板的生长和形成的透镜囊泡;缺乏Mab 2111的表达导致Foxe 3的表达减少，在一个细胞自主的方式。

We have immunopurified the mouse mab-21 gene Mab2111 as a target candidate for HOXC4. The mab-21 gene was first identified because of its requirement for ray identity specification in Caenorhabditis elegans. It is now known to constitute a family of genes that are highly conserved from vertebrates to invertebrates, and two homologs, Mab2111 and Mab2112, have been identified in many species. We describe the generation of Mab2111-deficient mice with defects in eye and preputial gland formation. The mutant mouse eye has a rudimentary lens resulting from insufficient invagination of the lens placode caused by deficient proliferation. Chimera analyses suggest that the lens placode is affected in a cell-autonomous manner, although Mab2111 is expressed in both the lens placode and the optic vesicle. The defects in lens placode development correlate with delayed and insufficient expression of Foxe3, which is also required for lens development, while Maf, Sox2, Six3 and PAX6 levels are not significantly affected. Significant reduction of Mab2111 expression in the optic vesicle and overlying surface ectoderm in Sey homozygotes indicates that Mab2111 expression in the developing eye is dependent upon the functions of Pax6 gene products. We conclude that Mab2111 expression dependent on PAX6 is essential for lens placode growth and for formation of the lens vesicle ; lack of Mab2111 expression causes reduced expression of Foxe3 in a cell-autonomous manner.