Incudomalleal joint formation: the roles of apoptosis, migration and downregulation
Incudomalleal joint formation: the roles of apoptosis, migration and downregulation
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DOI：
10.1186/1471-213x-7-134
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发表时间：
2007-12-05
影响因子：
--
通讯作者：
Tucker, Abigail S.
中科院分区：
文献类型：
--
作者：
Amin, Susan;Matalova, Eva;Tucker, Abigail S.
背景：哺乳动物中耳由镫骨、锤骨和砧骨三个内分泌小骨组成。关节连接锤骨和砧骨以及镫骨和镫骨。在小鼠中，源自锤骨和砧骨的第一弓由单个Sox 9和II型胶原蛋白表达缩合形成，所述缩合随后细分以产生两个单独的听小骨。与此相反，镫骨是由第二鳃弓的一个单独的冷凝物形成的。锤骨和砧骨的融合在许多人类综合征中被观察到，并导致传导性听力损失。了解如何在正常发展过程中，这种联合的形式，因此是一个重要的一步，在进一步了解这样的defects.Results：我们表明，发展中的incudomalleal联合的特点是缺乏增殖和离散区域的细胞凋亡。细胞凋亡已被认为有助于从关节区域去除前软骨细胞，允许软骨元素的物理分离，然而，我们表明，联合启动不受细胞凋亡的影响。也没有证据表明细胞迁移出假定的关节区域，如通过标记培养物中的关节和听小骨细胞所观察到的。然而，使用II型胶原lacZ报告小鼠，很明显，在假定的关节区域的细胞保持在原位，下调软骨markers.Conclusion：锤骨和砧骨首先出现作为一个单一的联合冷凝表达早期软骨标记。砧锤关节区是由假定关节区的细胞关闭软骨标记并打开关节标记形成的。该过程的失败可能导致该关节的融合，如在人类综合征如鳃-耳-肾综合征或Treacher柯林斯综合征中所观察到的。
Background: The middle ear of mammals is composed of three endochondrial ossicles, the stapes, incus and malleus. Joints link the malleus to the incus and the incus to the stapes. In the mouse the first arch derived malleus and incus are formed from a single Sox9 and Type II collagen expressing condensation that later subdivides to give rise to two separate ossicles. In contrast the stapes forms from a separate condensation derived from the second branchial arch. Fusion of the malleus and incus is observed in a number of human syndromes and results in conductive hearing loss. Understanding how this joint forms during normal development is thus an important step in furthering our understanding of such defects.Results: We show that the developing incudomalleal joint is characterised by a lack of proliferation and discrete areas of apoptosis. Apoptosis has been suggested to aid in the removal of precartilaginous cells from the joint region, allowing for the physical separation of the cartilaginous elements, however, we show that joint initiation is unaffected by blocking apoptosis. There is also no evidence of cell migration out of the presumptive joint region, as observed by labelling of joint and ossicle cells in culture. Using Type II collagen lacZ reporter mice, however, it is evident that cells in the presumptive joint region remain in place and downregulate cartilage markers.Conclusion: The malleus and incus first appear as a single united condensation expressing early cartilage markers. The incudomalleal joint region forms by cells in the presumptive joint region switching off cartilage markers and turning on joint markers. Failure in this process may result in fusion of this joint, as observed in human syndromes such as Branchio-Oto-Renal Syndrome or Treacher Collins Syndrome.