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Region-specific endodermal signals direct neural crest cells to form the three middle ear ossicles

 Harinarayana Ankamreddy  ;  Hyehyun Min  ;  Jae Yoon Kim  ;  Xiao Yang  ;  Eui-Sic Cho  ;  Un-Kyung Kim  ;  Jinwoong Bok 
 DEVELOPMENT, Vol.146(2) : dev167965, 2019 
Journal Title
Issue Date
Bone morphogenetic protein 4 ; Conductive hearing loss ; Endoderm ; Middle ear ; Mouse ; Neural crest ; Ossicles ; Sonic hedgehog
Defects in the middle ear ossicles - malleus, incus and stapes - can lead to conductive hearing loss. During development, neural crest cells (NCCs) migrate from the dorsal hindbrain to specific locations in pharyngeal arch (PA) 1 and 2, to form the malleus-incus and stapes, respectively. It is unclear how migratory NCCs reach their proper destination in the PA and initiate mesenchymal condensation to form specific ossicles. We show that secreted molecules sonic hedgehog (SHH) and bone morphogenetic protein 4 (BMP4) emanating from the pharyngeal endoderm are important in instructing region-specific NCC condensation to form malleus-incus and stapes, respectively, in mouse. Tissue-specific knockout of Shh in the pharyngeal endoderm or Smo (a transducer of SHH signaling) in NCCs causes the loss of malleus-incus condensation in PA1 but only affects the maintenance of stapes condensation in PA2. By contrast, knockout of Bmp4 in the pharyngeal endoderm or Smad4 (a transducer of TGFβ/BMP signaling) in the NCCs disrupts NCC migration into the stapes region in PA2, affecting stapes formation. These results indicate that region-specific endodermal signals direct formation of specific middle ear ossicles.
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1. College of Medicine (의과대학) > BioMedical Science Institute (의생명과학부) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Anatomy (해부학교실) > 1. Journal Papers
Yonsei Authors
Min, Hye Hyun(민혜현) ORCID logo https://orcid.org/0000-0001-5450-5088
Bok, Jin Woong(복진웅) ORCID logo https://orcid.org/0000-0003-1958-1872
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