The Chromatin Regulator Ankrd11 Controls Palate and Cranial Bone Development

Area of Science:

• Developmental Biology
• Genetics
• Craniomaxillofacial Surgery

Background:

• Epigenetic regulation of craniofacial development is not well understood.
• Ankyrin Repeat Domain 11 (ANKRD11) is a chromatin regulator involved in neural stem cell fates.
• Variants in ANKRD11 cause KBG syndrome, a disorder with craniofacial abnormalities.

Purpose of the Study:

• To investigate the role of ANKRD11 in embryonic craniofacial development.
• To explore the function of ANKRD11 in ossification and palate formation.
• To establish mouse models for KBG syndrome.

Main Methods:

• Analysis of 3D images from KBG syndrome patients.
• Generation of heterozygous (Ankrd11^nchet) and homozygous (Ankrd11^ncko) Ankrd11 deletion mouse models in neural crest cells.
• Examination of craniofacial development, gene expression, ossification, and palate formation in mouse models.

Main Results:

• Ankrd11^nchet mice exhibit midfacial hypoplasia and persistent open fontanelle, mirroring KBG syndrome phenotypes.
• Ankrd11^ncko mice display severe cleft palate, retrognathia, midfacial hypoplasia, and reduced calvarial growth, dying at birth.
• Conditional deletion of Ankrd11 impairs midfacial bone ossification and delays intramembranous bone maturation.
• Palatal shelves remain hypoplastic due to reduced proliferation.

Conclusions:

• ANKRD11 is essential for intramembranous ossification and palate development.
• Ankrd11^nchet and Ankrd11^ncko mice serve as valuable preclinical models for KBG syndrome.
• Understanding ANKRD11's role provides insights into craniofacial development and related disorders.