SAG, a specific Hh signalling activator, is reported to enhance bone healing in a bone defect model.43 Supplemental SAG can also promote neural regeneration after ischaemic brain injury.44 In our in vivo experiment, we found that SAG injection significantly improves mandibular bone mass reduction caused by Bmal1 knockout at prepuberty and early puberty periods rather than young adulthood, suggesting that SAG may be the potential candidates as novel therapeutic strategies for preventing the facial dysmorphism. Here, SAG is linked to brain injury.