Moribe H, Takagi T, Kondoh H, Higashi Y
Institute for Molecular and Cellular Biology, Osaka University, Suita, Japan.
Dev Growth Differ. 2000 Aug;42(4):367-76. doi: 10.1046/j.1440-169x.2000.00523.x.
Digit patterning is established through multiple genetic interactions. Delta-crystallin enhancer/E2-box factor (deltaEF1) is a zinc finger and homeodomain containing repressor protein, and is expressed in the posterior half of the forelimb bud and in the entire hindlimb bud during the early stage of limb development. The 6EF1-deficient mutant mice display various skeletal abnormalities, among which inferior ossification and abnormal patterning of autopodial bones are similar to those observed in Hox and Gli gene mutants. Gli3 mutant mice, extra toes (Xt), exhibit pre-axial polydactyly losing the identity of digit I. It is demonstrated here that deltaEF1null(lacZ) homozygosity suppressed formation of the extra digit, uniquely of the hindlimb, in both Gli3XtJ heterozygous and homozygous mutants, but with no restoration of digit I identity. In Gli3XtJ mutants, the Hoxd13 expression domain was expanded more dramatically in homozygotes. In Gli3XtJ;deltaEF1null(lacZ) double homozygous mutants, Hoxd13 expression once expanded in Gli3XtJ homozygous mutant was reduced, more conspicuously in the hindlimbs, which may account for hindlimb-restricted suppression of formation of the extra digit. The data suggest the possibility that the extent of Hoxd13 expression along the distal margin of the limb bud is determinative in defining the digit number.
指（趾）模式是通过多种基因相互作用建立的。δ-晶体蛋白增强子/E2-盒因子（δEF1）是一种含有锌指和同源结构域的阻遏蛋白，在肢体发育早期在前肢芽的后半部分和整个后肢芽中表达。δEF1缺陷型突变小鼠表现出各种骨骼异常，其中自手（足）骨的骨化不良和模式异常与在Hox和Gli基因突变体中观察到的相似。Gli3突变小鼠extra toes（Xt）表现出轴前多指畸形，失去了指（趾）I的特征。本文证明，在Gli3XtJ杂合子和纯合子突变体中，δEF1null（lacZ）纯合性抑制了额外指（趾）的形成，且仅在后肢中出现，但并未恢复指（趾）I的特征。在Gli3XtJ突变体中，Hoxd13表达域在纯合子中扩展得更为显著。在Gli3XtJ；δEF1null（lacZ）双纯合突变体中，在Gli3XtJ纯合突变体中一度扩展的Hoxd13表达降低，在后肢中更为明显，这可能解释了后肢特异性地抑制额外指（趾）的形成。这些数据表明，沿着肢体芽远端边缘的Hoxd13表达程度在确定指（趾）数量方面具有决定性作用。
