Heanue Tiffany A, Davis Richard J, Rowitch David H, Kispert Andreas, McMahon Andrew P, Mardon Graeme, Tabin Clifford J
Department of Genetics, Harvard Medical School, Boston, MA 02115, USA.
Mech Dev. 2002 Feb;111(1-2):75-87. doi: 10.1016/s0925-4773(01)00611-6.
We have cloned a chick homologue of Drosophila dachshund (dac), termed Dach1. Dach1 is the orthologue of mouse and human Dac/Dach (hereafter referred to as Dach1). We show that chick Dach1 is expressed in a variety of sites during embryonic development, including the eye and ear. Previous work has demonstrated the existence of a functional network and genetic regulatory hierarchy in Drosophila in which eyeless (ey, the Pax6 orthologue), eyes absent (eya), and dac operate together to regulate Drosophila eye development, and that ey regulates the expression of eya and dac. We find that in the developing eye of both chick and mouse, expression domains of Dach1 overlap with those of Pax6, a gene required for normal eye development. Similarly, in the developing ear of both mouse and chick, Dach1 expression overlaps with the expression of another Pax gene, Pax2. In the mouse, Dach1 expression in the developing ear also overlaps with the expression of Eya1 (an eya homologue). Both Pax2 and Eya1 are required for normal ear development. Our expression studies suggest that the Drosophila Pax-eya-dac regulatory network may be evolutionarily conserved such that Pax genes, Eya1, and Dach1 may function together in vertebrates to regulate neural development. To address the further possibility that a regulatory hierarchy exists between Pax, Eya, and Dach genes, we have examined the expression of mouse Dach1 in Pax6, Pax2 and Eya1 mutant backgrounds. Our results indicate that Pax6, Pax2, and Eya1 do not regulate Dach1 expression through a simple linear hierarchy.
我们克隆了果蝇“腊肠犬”基因(dac)的一个鸡同源基因,命名为Dach1。Dach1是小鼠和人类Dac/Dach(以下简称Dach1)的直系同源基因。我们发现,鸡Dach1在胚胎发育过程中在多种组织中表达,包括眼睛和耳朵。先前的研究表明,果蝇中存在一个功能性网络和遗传调控层级,其中无眼基因(ey,Pax6的直系同源基因)、无眼相关基因(eya)和dac共同作用来调控果蝇眼睛发育,且ey调控eya和dac的表达。我们发现,在鸡和小鼠发育中的眼睛里,Dach1的表达域与正常眼睛发育所需的Pax6基因的表达域重叠。同样,在小鼠和鸡发育中的耳朵里,Dach1的表达与另一个Pax基因Pax2的表达重叠。在小鼠中,发育中耳朵里的Dach1表达也与Eya1(eya的同源基因)的表达重叠。Pax2和Eya1都是正常耳朵发育所必需的。我们的表达研究表明,果蝇的Pax-eya-dac调控网络可能在进化上是保守的,使得Pax基因、Eya1和Dach1可能在脊椎动物中共同作用来调控神经发育。为了进一步探究Pax、Eya和Dach基因之间是否存在调控层级,我们检测了Pax6、Pax2和Eya1突变背景下小鼠Dach1的表达。我们的结果表明,Pax6、Pax2和Eya1并非通过简单的线性层级来调控Dach1的表达。