Abstract
Human midfacial clefting is a rare subset of orofacial clefting and in severe cases, the cleft separates the nostrils splitting the nose into two independent structures. To begin to understand the morphological and genetic causes of midfacial clefting we recovered the Unicorn mouse line. Unicorn embryos develop a complete midfacial cleft through the lip, and snout closely modelling human midfacial clefting. The Unicorn mouse line has ethylnitrosourea (ENU)-induced missense mutations in Raldh2 and Leo1. The mutations segregate with the cleft face phenotype. Importantly, the nasal cartilages and surrounding bones are patterned and develop normal morphology, except for the lateral displacement because of the cleft. We conclude that the midfacial cleft arises from the failure of the medial convergence of the paired medial nasal prominences between E10.5 to E11.5 rather than defective cell proliferation and death. Our work uncovers a novel mouse model and mechanism for the etiology of midfacial clefting.
Original language | English (US) |
---|---|
Article number | 83 |
Journal | Genes |
Volume | 11 |
Issue number | 1 |
DOIs | |
State | Published - Jan 2020 |
Funding
Funding: The authors are grateful for the support by P30-NIH-DE020740 and start-up funds from the University of Pittsburgh School of Dental Medicine (HLSR). In addition, Brandi Lantz was supported by an Oral Biology Graduate student award. Casey White was supported by the Dean’s Summer Scholar Program.
Keywords
- Leo1
- Medial nasal prominences
- Midfacial clefting
- Nasal septum
- Raldh2
- Unicorn
ASJC Scopus subject areas
- Genetics
- Genetics(clinical)