| The central nervous system(CNS)of vertebrates controls body sensations,movements,emotions and behaviors,thus playing critical roles in individual survival and reproduction.The central nervous system is composed of neurons,oligodendrocytes(OLs)and astrocytes.OLs can form myelin sheathes along axons which accelerates the transmitting speed of nerve impulse and provide nutrition support for myelinated axons in CNS.Our previous studies demonstrated that NK2 homeobox 2(Nkx2.2)functions as a transcriptional repressor to govern the timing of oligodendrocyte differentiation via disturbing the expression of Pdgfra.However,the detailed molecular mechanism is still unknown.In this study,we identified the repressor domains that mediate OLs differentiation through in ovo electroporation in embryonic chicken spinal cords,the N-terminal Tinman(TN)domain and C-terminal(CT)domain.These two domains act synergistically to promote OLs differentiation by recruiting distinct transcriptional co-repressors including GRG3,HDAC1 and DNMT3 A.In contrast,the NK2-specific domain(SD)negatively regulates the function of TN and CT domain in promoting OLs differentiation.These findings suggested that the different domains of NKX2.2 have distinct roles in regulating OLs differentiation,suggesting the multiple molecular mechanisms of Nkx2.2 in controlling OLs differentiation.In CNS,neurons produce and transmit electrical impulse.In this study,we found that NKX2.2 is highly expressed in hypothalamic neurons of paraventricular nucleus(PVN)and ventromedial nucleus(VMN),which are involved in obesity.Conditional deletion of Nkx2.2 from these neurons in mouse via Olig1-Cre caused severe obesity due to hyperphagia.Further analysis suggested that the obesity of Nkx2.2 CKO mouse may be caused by the abnormal arrangement of magnocellular neurons in PVN,but not VMN.Taken together,these results suggested that the deficiency of Nkx2.2 is an important reason for hyperphagia and obesity,and these findings provided a novel avenue for the treatment of obesity. |
