PMID- 32319178 OWN - NLM STAT- MEDLINE DCOM- 20211007 LR - 20211007 IS - 1097-0177 (Electronic) IS - 1058-8388 (Linking) VI - 249 IP - 9 DP - 2020 Sep TI - CXCL12 is required for stirrup-shaped stapes formation during mammalian middle ear development. PG - 1117-1126 LID - 10.1002/dvdy.180 [doi] AB - BACKGROUND: The mammalian middle ear comprises a chain of three ossicles-the malleus, incus, and stapes-each of which has a unique morphology for efficiently transmitting sound information. In particular, the stapes, which is attached to the inner ear, is stirrup-shaped with a head and base connected by two crural arches, forming the stapedial foramen, through which the stapedial artery passes. However, how the stapes acquires this critical stirrup shape for association with the stapedial artery during development is not clear. RESULTS: C-X-C motif chemokine ligand 12 (CXCL12) is a chemoattractant essential for cellular movement and angiogenesis. In Cxcl12 (-/-) embryos, migration of neural crest cells into the prospective middle ear regions and their mesenchymal condensation to form the three ossicles proceed normally in correct alignment with each other and the inner ear. However, in the absence of CXCL12, the stapes loses its stirrup shape and instead exhibits a columnar shape lacking the crural arches and central hole. In addition, although the stapedial artery initially forms during early mesenchymal condensation of the stapes, it degenerates without CXCL12 function. CONCLUSION: CXCL12 plays an essential role in establishing the stirrup-shaped architecture of the stapes, possibly by maintaining the stapedial foramen and stapedial artery throughout development. CI - (c) 2020 Wiley Periodicals, Inc. FAU - Ankamreddy, Harinarayana AU - Ankamreddy H AD - Department of Anatomy, Yonsei University College of Medicine, Seoul, South Korea. AD - BK21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul, South Korea. FAU - Koo, Heiyeun AU - Koo H AD - Department of Anatomy, Yonsei University College of Medicine, Seoul, South Korea. AD - BK21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul, South Korea. FAU - Lee, Young Jae AU - Lee YJ AD - Lee Gil Ya Cancer and Diabetes Institute, Gachon University, Incheon, South Korea. FAU - Bok, Jinwoong AU - Bok J AUID- ORCID: 0000-0003-1958-1872 AD - Department of Anatomy, Yonsei University College of Medicine, Seoul, South Korea. AD - BK21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul, South Korea. AD - Department of Otorhinolaryngology, Yonsei University College of Medicine, Seoul, South Korea. LA - eng GR - 2014M3A9D5A01073865/National Research Foundation of Korea/International GR - 2016R1A5A2008630/National Research Foundation of Korea/International GR - 2017R1A2B3009133/National Research Foundation of Korea/International PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20200502 PL - United States TA - Dev Dyn JT - Developmental dynamics : an official publication of the American Association of Anatomists JID - 9201927 RN - 0 (Chemokine CXCL12) RN - 0 (Cxcl12 protein, mouse) SB - IM MH - Animals MH - Chemokine CXCL12/genetics/*metabolism MH - Ear, Middle/cytology/*embryology MH - Embryo, Mammalian/cytology/*embryology MH - Mice MH - Mice, Knockout MH - *Organogenesis OTO - NOTNLM OT - CXCL12 OT - middle ear OT - ossicle OT - stapedial artery OT - stapedial foramen OT - stapes EDAT- 2020/04/23 06:00 MHDA- 2021/10/08 06:00 CRDT- 2020/04/23 06:00 PHST- 2019/11/16 00:00 [received] PHST- 2020/04/17 00:00 [revised] PHST- 2020/04/17 00:00 [accepted] PHST- 2020/04/23 06:00 [pubmed] PHST- 2021/10/08 06:00 [medline] PHST- 2020/04/23 06:00 [entrez] AID - 10.1002/dvdy.180 [doi] PST - ppublish SO - Dev Dyn. 2020 Sep;249(9):1117-1126. doi: 10.1002/dvdy.180. Epub 2020 May 2.