Craniofacial bone loss in children is a challenging clinical problem for which no regenerativestrategies are available. This type of bone loss is primarily treated with autologous bone grafting. Congenital absence of bone in the maxillary area is a defining facial characteristic of Alagille syndrome patients and may require bone grafting to restore maxillary alignment. Alagille syndrome is an autosomal dominantly inherited disorder that occurs primarily due to mutations in JAGGED1 and is associated with cardiac, biliary and bone phenotypes. Children with Alagille syndrome not only have maxillary bone hypoplasia, they also suffer from frequent bony fractures. Adults with Alagille syndrome have reduced bone mineral density and genome wide association studies revealed Single Nucleotide Polymorphisms in JAGGED1 were associated with reduced bone mineral density in otherwise unaffected adults. Together these data highlight the requirement of Jagged1 signaling during bone formation and that its absence causes multiple bony phenotypes, most noticeably maxillary hypoplasia. Jagged1 regulates multiple cell functions including cell survival, cell migration, and cell fate determination. Our initial work has established the requirement of Jagged1 during cranial neural crest (CNC) bone formation through the generation of a mouse model of Alagille syndrome with maxillary bone loss.