JAGGED1 mutations cause Alagille syndrome, comprising a constellation of 
clinical findings, including biliary, cardiac and craniofacial anomalies. 
Jagged1, a ligand in the Notch signaling pathway, has been extensively studied 
during biliary and cardiac development. However, the role of JAGGED1 during 
craniofacial development is poorly understood. Patients with Alagille syndrome 
have midface hypoplasia giving them a characteristic 'inverted V' facial 
appearance. This study design determines the requirement of Jagged1 in the 
cranial neural crest (CNC) cells, which encompass the majority of mesenchyme 
present during craniofacial development. Furthermore, with this approach, we 
identify the autonomous and non-autonomous requirement of Jagged1 in a cell 
lineage-specific approach during midface development. Deleting Jagged1 in the 
CNC using Wnt1-cre; Jag1 Flox/Flox recapitulated the midfacial hypoplasia 
phenotype of Alagille syndrome. The Wnt1-cre; Jag1 Flox/Flox mice die at 
postnatal day 30 due to inability to masticate owing to jaw misalignment and 
poor occlusion. The etiology of midfacial hypoplasia in the Wnt1-cre; Jag1 
Flox/Flox mice was a consequence of reduced cellular proliferation in the 
midface, aberrant vasculogenesis with decreased productive vessel branching and 
reduced extracellular matrix by hyaluronic acid staining, all of which are 
associated with midface anomalies and aberrant craniofacial growth. Deletion of 
Notch1 from the CNC using Wnt1-cre; Notch1 F/F mice did not recapitulate the 
midface hypoplasia of Alagille syndrome. These data demonstrate the requirement 
of Jagged1, but not Notch1, within the midfacial CNC population during 
development. Future studies will investigate the mechanism in which Jagged1 acts 
in a cell autonomous and cell non-autonomous manner.