Samantha Kitchen
Pronouns: she/her
Research Mentor(s): Yuji Mishina
Research Mentor School/College/Department: Biological and Material Sciences / Dentistry
Program:
Authors: Samantha Kitchen, Haichun Pan, Yuji Mishina
Session: Session 4: 1:40 pm – 2:30 pm
Poster: 104
Abstract
Bone development abnormalities in the craniofacial area are heavily paired with the need for lifelong treatment in afflicted patients. Throughout embryo formation, genetic signaling factors influence the behavioral functions of cells, therefore regulating the formation of bone structure in the face. Bone morphogenetic protein (BMP) signaling in cranial neural crest cells (CNCCs) is a determinant of histone lactylation through the glycolytic production of lactate, which affects the expression of craniofacial cells and therefore the structure of the cranium. In constitutively activated ACVR1, a receptor protein controlling bone growth and development, increased BMP signaling blocked lactate production, resulting in midline facial defects. It has been reported that exogenous sodium lactate promotes histone lactylation, therefore examination of this sodium lactate supplementation treatment was performed on ca-ACVR1 mutant cells to assess whether or not they could be rescued. Treatment was performed on pregnant female mice E8.5-E11.5 via intraperitoneal injection, and it was found through the comparison of mutant and wild type mice that the recovery of glycolytic activity in CNCCs rescued the histone lactylation and craniofacial defects of ca-ACVR1 mutants. These findings demonstrate how BMP signaling directs craniofacial bone formation, particularly during embryonic development, and reveals that the reduced lactate production of mutant mice is responsible for the midline facial defects observed in the ca-ACVR1 mutants. This regulation of histone lactylation suggests possible future preventative strategies for congenital facial defects.
