Tvrdik Petr, Capecchi Mario R
Howard Hughes Medical Institute, University of Utah, 15 North 2030 East, Salt Lake City, Utah 84112, USA.
Dev Cell. 2006 Aug;11(2):239-50. doi: 10.1016/j.devcel.2006.06.016.
In vertebrates, paralogous Hox genes play diverse biological roles. We examined the interchangeability of Hoxa1 and Hoxb1 in mouse development by swapping their protein-coding regions. Remarkably, the mice expressing the Hox-B1 protein from the Hoxa1 locus, and vice versa, are essentially normal. We noted, nonetheless, a specific facial nerve hypomorphism in hemizygous Hoxb1(A1/-) mice and decreased viability in homozygous Hoxa1(B1/B1) embryos. Further, we established a mouse line in which we have inserted the 107 bp Hoxb1 autoregulatory enhancer into the Hoxa1 promoter. Strikingly, the newly generated autoregulatory Hoxa1 gene can deliver the functionality of both paralogs in these mice, providing normal viability as well as proper facial nerve formation even in the Hoxb1 mutant background. This study affirms that subfunctionalization of the transcriptional regulatory elements has a principal role in the diversification of paralogous Hox genes. Moreover, we show that the ancestral vertebrate Hox1 gene can still be experimentally reconstructed.
在脊椎动物中，同源的Hox基因发挥着多样的生物学作用。我们通过交换Hoxa1和Hoxb1的蛋白质编码区域，研究了它们在小鼠发育过程中的互换性。值得注意的是，从Hoxa1基因座表达Hox - B1蛋白的小鼠，反之亦然，基本上是正常的。然而，我们注意到半合子Hoxb1(A1/-)小鼠存在特定的面神经发育不全，并且纯合子Hoxa1(B1/B1)胚胎的生存能力下降。此外，我们建立了一个小鼠品系，其中我们将107 bp的Hoxb1自调控增强子插入到Hoxa1启动子中。令人惊讶的是，新产生的自调控Hoxa1基因能够在这些小鼠中发挥两个同源基因的功能，即使在Hoxb1突变背景下也能提供正常的生存能力以及正常的面神经形成。这项研究证实，转录调控元件的亚功能化在同源Hox基因的多样化中起主要作用。此外，我们表明，仍然可以通过实验重建祖先脊椎动物的Hox1基因。
