Evolution, Function and Regulation of Teleost Hox Genes

在后生动物胚胎发育过程中，HOX基因沿前后轴构建模式。HOX簇复制事件伴随着脊椎动物的起源，并提供了额外的图案信息，可能允许出现更复杂的身体计划。P.I.和其他人最近的工作证实，在硬骨鱼谱系中，一个额外的基因组复制事件导致了四足动物和硬骨鱼的Hox组织和补体之间的显着差异。本研究将以斑马鱼前向表达的类群(Pg)1中的Hox基因为样本，比较和比较不同脊椎动物类群中的基因功能和调控，从而研究进化过程中Hox基因的修饰。初步研究表明，斑马鱼PG1 Hox基因在组织、表达和潜在功能方面与小鼠等四足类脊椎动物有显著差异。因此，斑马鱼hoxa1a以一种与同源小鼠HOXA-1基因完全不同的方式表达，在腹侧中脑具有一个新的前表达结构域。此外，青竹这种远亲硬骨鱼也有同样的中脑表达。这项研究将采用更广泛的比较方法来确定在脊椎动物进化过程中，这种前向表达是何时出现的。相反，斑马鱼hoxb1b基因的表达模式与非同源小鼠HOXA-1基因的表达模式非常相似。初步实验已经证实，PG1基因的错误表达会导致典型的后脑同源同源转化。总之，这些数据表明斑马鱼hoxb1b在功能上等同于小鼠HOXA-1的假设；这一假设将使用基于反义吗啉RNA的新的功能丧失方法直接进行验证。类似的方法将被用来测试复制基因hoxb1a的功能冗余或协同作用。

0091101PrinceThe Hox genes set up pattern along the anteroposterior axis of developing metazoan embryos. Hox cluster duplication events accompanied vertebrate origins and provided additional patterning information, likely allowing for more complex body plans to arise. Recent work from the P.I. and others has established that in the teleost lineage an additional genome duplication event has led to significant differences between the Hox organization and complement of tetrapods and teleosts. This study will focus on zebrafish hox genes in the anteriorly expressed paralogue group (PG) 1 as a paradigm to compare and contrast gene function and regulation in different vertebrate groups and hence to investigate Hox gene modification during evolution.Preliminary studies have shown that the zebrafish PG1 hox genes are significantly different in terms of organization, expression, and potential function, from those of the tetrapod vertebrates such as mouse. Thus, zebrafish hoxa1a is expressed in a completely different manner to the orthologous mouse Hoxa-1 gene, having a novel anterior expression domain in the ventral midbrain. Furthermore, midbrain expression is shared by medaka, a distantly related teleost species. This study will take a broader comparative approach to determine when in vertebrate evolution this anterior expression arose. Conversely, the zebrafish hoxb1b gene has an expression pattern remarkably similar to that of the non-orthologous mouse Hoxa-1 gene. Preliminary experiments have established that mis-expression of PG1 genes causes a classic posteriorizing homeotic transformation of the hindbrain. Together these data suggest the hypothesis that zebrafish hoxb1b is functionally equivalent to mouse Hoxa-1; this hypothesis will be tested directly using a novel loss-of-function approach based on antisense morpholino RNAs. A similar approach will be used to test redundancy or synergy of function with the duplicate gene hoxb1a.