Region-specific endodermal signals direct neural crest cells to form the three middle ear ossicles
Harinarayana Ankamreddy1,2, Hyehyun Min1, Jae Yoon Kim1,2
1Department of Anatomy, Yonsei University College of Medicine, Seoul, South Korea.
Development (Cambridge, England)
|January 12, 2019
Summary
Sonic hedgehog (SHH) and bone morphogenetic protein 4 (BMP4) from pharyngeal endoderm guide neural crest cells to form middle ear ossicles. Signaling pathways direct specific cell condensation for malleus-incus and stapes development.
Area of Science:
- Developmental biology
- Craniofacial development
- Molecular signaling
Background:
- Middle ear ossicles (malleus, incus, stapes) are crucial for hearing.
- Defects in ossicles cause conductive hearing loss.
- Neural crest cells (NCCs) form ossicles in pharyngeal arches (PAs) 1 and 2, but guidance mechanisms are unclear.
Purpose of the Study:
- Investigate the role of pharyngeal endoderm signaling in directing NCCs for middle ear ossicle formation.
- Determine how sonic hedgehog (SHH) and bone morphogenetic protein 4 (BMP4) influence specific ossicle development.
Main Methods:
- Utilized tissue-specific knockout mouse models targeting SHH/Smo and BMP4/Smad4 signaling pathways.
- Analyzed NCC migration and mesenchymal condensation in pharyngeal arches 1 and 2.
- Examined the formation of malleus-incus and stapes.
Main Results:
- SHH signaling is crucial for malleus-incus condensation in PA1 and stapes maintenance in PA2.
- BMP4 signaling disruption affects NCC migration to the stapes region in PA2, impacting stapes formation.
- Region-specific endodermal signals dictate the formation of distinct middle ear ossicles.
Conclusions:
- Pharyngeal endoderm-derived SHH and BMP4 are essential for guiding NCCs to form specific middle ear ossicles.
- Distinct signaling pathways orchestrate the development of the malleus-incus and stapes.
- Understanding these molecular mechanisms provides insights into congenital hearing loss.
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