Author:
Amin Susan,Matalova Eva,Simpson Carol,Yoshida Hiroki,Tucker Abigail S
Abstract
Abstract
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 pre-cartilaginous 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.
Publisher
Springer Science and Business Media LLC
Reference55 articles.
1. Amin S, Tucker AS: Joint formation in the middle ear: lessons from the mouse and guinea pig. Dev Dyn. 2006, 235: 1326-33. 10.1002/dvdy.20666.
2. Miyake T, Cameron AM, Hall BK: Stage-specific onset of condensation and matrix deposition for Meckel's and other first arch cartilages in inbred C57BL/6 mice. J Craniofac Genet Dev Biol. 1996, 16: 32-47.
3. Bell DM, Leung KK, Wheatley SC, Hg LJ, Zhou S, Ling KW, Sham MH, Koopman P, Tam PP, Cheah KS: Sox9 directly regulates the type-II collagen gene. Nat Genet. 1997, 16: 174-178. 10.1038/ng0697-174.
4. Healy C, Uwanogho D, Sharpe PT: Regulation and role of Sox9 in cartilage formation. Dev Dyn. 1999, 215: 69-78. 10.1002/(SICI)1097-0177(199905)215:1<69::AID-DVDY8>3.0.CO;2-N.
5. Fleischer G: Evolutionary principles of the mammalian middle ear. Adv Anat Embryol Cell Biol. 1978, 55 (5): 3-70.
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