High Glucose Environment Inhibits Cranial Neural Crest Generation By Activating Excessive Autophagy In The Chick Embryo

AimsIn this study, we investigated the cellular and molecular mechanisms of the abnormal development of the cranial neural crest induced by hyperglycemia in the early chick embryo. MethodsChick embryos were treated with glucose. Then, the cranial neural crest derived cranial skeleton was observed. Subsequently, we studied the effect of high glucose on early development of cranial neural crest including gene expression, proliferation, apoptosis and autophagy. ResultsIn this study, we observed a defect in chick cranial skeleton, especially parietal bone development in the presence of high glucose levels, which is derived from cranial neural crest cells(CNCC). In early chick embryo, we found that inducing high glucose levels could inhibit the development of CNCC, however, cell proliferation was not significantly involved. Nevertheless, CNCC death increased in the presence of high levels of glucose. In addition, the expression of apoptosis relevant genes(P53, cleaved-Caspase3 and 7) and genes associated with autophagy(LC3B, truncated-Atg5 and Beclin-1) was elevated by high glucose treatment in HEK293 T cells. Next, the application of beads soaked in either an autophagy stimulator(Tunicamycin) or inhibitor(Hydroxychlorochin) functionally proved that autophagy was involved in regulating the production of cranial neural crest cell in the presence of high glucose levels. Our observations suggest that the ERK pathway, rather than the m TOR pathway, most likely possesses a more important role in mediating the autophagy induced by high glucose. Conclusions/interpretationOur observations indicated that exposure to high levels of glucose could inhibit the production of cranial neural crest cell by affecting cell death, which might result from the dysregulation of the autophagic process.