Explore The Role Of Histone Methyltransferase Setdbl In The Development Of Cerebellar Neurons

More and more studies have shown that the development of neurons is closely related to epigenetic modification.Epigenetic regulation of cerebellar development and related diseases is rarely reported,and the mechanism between them is not clear.The level of histone H3K9me3 was reported to be associated with the antidepressant ability of mice,and theH3K9me3 methyltransferase setdbl was mutated in the autistic patients.We found that Setdb1,histone H3 Lsy9(H3K9)methyltransferase,is highly expressed in the cerebellar neurons of mice.Our experimental results suggest that Setdb1 is highly expressed in the cerebellar neurons,suggesting that Setdb1 may play a significant role in the development of neurons in the cerebellum.We constructed a Mathl promoter driven Cre knockout mouse,which specifically knocked out Setdb1 in the mouse cerebellar granular precursor cells(GNP),and we also constructed the Cre knockout mouse driven by the PCP2 promoter,which could be specifically in the mouse cerebellar Purkinje cells,as a result of the death of the mouse embryo caused by the systemic knockout of Setdbl.Knock out Setdbl to study the effect of Setdbl on the development of cerebellar nervous system in mice.The mice in the experimental group of Math1-Cre could have normal survival and fertility,but the mice in the experimental group showed a weaker balance and learning ability in the behavioral test of the balance wheel(Rotarod).So we explored the molecular mechanisms in it.The results of immunehistochemical H&E staining showed that the granular cell layer of the mice was obviously thinner.We did the proliferation and apoptosis experiments of the granular precursor cells(GNP).It was found that the proliferation of the granular precursor cells was seriously affected.It was conjecture that the differentiation and maturation of the granular precursor cells may be different.The differentiation of precursors in the granular cells appeared ahead of time,and the phenomenon of maturation and migration lagged behind.During this process,Bergmann glial cells,Purkinje cells and oligodendrocytes cell lines were not affected.We need to do autism related behavioral tests,to observe the autism of mice,and to explore the relevant molecular mechanisms to provide a theoretical basis for the treatment of autism.There was no abnormality in the balance ability and the structure of the cerebellum in the experimental group of PCP2-Cre.Granular cells and oligodendrocytes were not affected.Next,a preliminary exploration of the molecular mechanism is carried out.The mice deficient in Setdbl's Purkinje cells may not be abnormally due to the fact that the expression of PCP2-Cre was born after birth,and after birth,the Purkinje cells were mature,and knockout Setdbl in the mature Purkinje cells did not affect its development.