Bapx1 regulates patterning in the middle ear:: altered regulatory role in the transition from the proximal jaw during vertebrate evolution
Bapx1 regulates patterning in the middle ear:: altered regulatory role in the transition from the proximal jaw during vertebrate evolution
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DOI：
10.1242/dev.01017
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发表时间：
2004-03-01
期刊：
影响因子：
4.6
通讯作者：
Hill, RE
中科院分区：
文献类型：
--
作者：
Tucker, AS;Watson, RP;Hill, RE
中耳装置由三个内听小骨（镫骨、砧骨和锤骨）和两个膜骨（鼓环和前角）组成，其充当将听小骨锚到颅骨的结构部件。除了镫骨，这些骨骼元素是哺乳动物所独有的，来自第一和第二鳃弓。我们发现，在结合goosecoid（GSC），Bapx1基因定义的结构组成部分的小鼠middleear.During胚胎发育，Bapx1表达在一个离散的域内的下颌组成部分的第一鳃弓，后来在原基的中耳相关的骨头，生殖器和鼓膜环。与Bapx1的表达模式一致，缺乏Bapx1的小鼠胚胎缺乏生殖器，并显示鼓膜环前端发育不全。在E10.5，Bapx1的表达部分重叠的GSC，虽然GSC是所需的整个鼓膜环的发展，Bapx1的作用是有限的生殖器和前鼓膜环的规格。因此，这两个基因的简单重叠表达似乎可以解释组成中耳结构成分的元件的模式，并表明它们协同作用。此外，Bapx1在砧骨和锤骨内和周围都有表达。对锤骨的检查表明，突变小鼠的听骨宽度减少，但长度没有减少。在非哺乳类有颌脊椎动物中，与哺乳类中耳小骨同源的骨骼组成了形成颌关节（初级颌关节）的近端颌骨。在鱼类中，Bapx1负责形成方骨和关节（锤骨和砧骨的同源物）之间的关节，从而能够对近端颌骨向中耳小骨过渡中调控基因的作用进行进化比较。与预期相反，小鼠Bapx1不影响锤骨和砧骨的关节。我们表明，这种变化的作用Bapx1的过渡到哺乳动物听小骨配置是不是由于表达模式的变化，但从无法调节Gdf5和Gdf6，两个基因预测是必不可少的联合形成的结果。
The middle ear apparatus is composed of three endochondrial ossicles (the stapes, incus and malleus) and two membranous bones, the tympanic ring and the gonium, which act as structural components to anchor the ossicles to the skull. Except for the stapes, these skeletal elements are unique to mammals and are derived from the first and second branchial arches. We show that, in combination with goosecoid (Gsc), the Bapx1 gene defines the structural components of the murine middle ear.During embryogenesis, Bapx1 is expressed in a discrete domain within the mandibular component of the first branchial arch and later in the primordia of middle ear-associated bones, the gonium and tympanic ring. Consistent with the expression pattern of Bapx1, mouse embryos deficient for Bapx1 lack a gonium and display hypoplasia of the anterior end of the tympanic ring. At E10.5, expression of Bapx1 partially overlaps that of Gsc and although Gsc is required for development of the entire tympanic ring, the role of Bapx1 is restricted to the specification of the gonium and the anterior tympanic ring. Thus, simple overlapping expression of these two genes appears to account for the patterning of the elements that compose the structural components of the middle ear and suggests that they act in concert.In addition, Bapx1 is expressed both within and surrounding the incus and the malleus. Examination of the malleus shows that the width, but not the length, of this ossicle is decreased in the mutant mice. In non-mammalian jawed vertebrates, the bones homologous to the mammalian middle ear ossicles compose the proximal jaw bones that form the jaw articulation (primary jaw joint). In fish, Bapx1 is responsible for the formation of the joint between the quadrate and articular (homologues of the malleus and incus, respectively) enabling an evolutionary comparison of the role of a regulatory gene in the transition of the proximal jawbones to middle ear ossicles. Contrary to expectations, murine Bapx1 does not affect the articulation of the malleus and incus. We show that this change in role of Bapx1 following the transition to the mammalian ossicle configuration is not due to a change in expression pattern but results from an inability to regulate Gdf5 and Gdf6, two genes predicted to be essential in joint formation.