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The Function Of Brg1 In The Development Of Cerebral Cortex In Mice

Posted on:2020-05-07Degree:MasterType:Thesis
Country:ChinaCandidate:X T GaoFull Text:PDF
GTID:2370330572971402Subject:Developmental Biology
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The cerebral cortex is the most advanced center that controls the movement of the body.The functions of the body are regulated by the cooperation of the brain and spinal cord under the cortex.The cerebral cortex must precisely coordinate each major event and process during its development,establishing the basis for the structure and function of the brain.Misregulation due to genetic or environmental damage can lead to cognitive defects,neurodevelopmental disorders,and other diseases.The normal development of the cerebral cortex plays an important role in the function of the central nervous system.Although past researches have provided some clues to the formation of the cerebral cortex,the molecular mechanisms affecting the development of the cerebral cortex are not clear.Brgl is the core hydrolase subunit of the SWI/SNF chromatin recombination complex,which provides chromosomal recombination by ATP hydrolysis to regulate gene expression.Functional studies of Brel in a variety of tissues have been reported,including liver,lung,eye,cochlea,hair follicle,heart,blood vessels,germ cells,urinary system,etc.,and play different roles in the differentiation and development of many tissues.In the study of the central nervous system,it was found that Brg1 affects neurogenesis,neurogenesis and synaptogenesis.indicating that Brg1 plays an important role in neurodevelopment.However,the mechanism which Brgl regulates the development of the cerebral cortex is not clear.Since Brg1 knockdown mice died during embryonic stage,we used the Cre/LoxP system to construct a model of Brgl cerebral cortical conditional knockout mouse to study the function of Brg1 in corticogenesisc of mice.In this paper,we found that Brgl is highly expressed in the ear-ly stages of cerebral cortex development and gradually decreases as development progresses.By anatomy,the brain of Brg1 knockout mice became smaller and the cerebral cortex was thin and transparent.HE staining of tissue sections further showed that the cerebral cortex morphology was significantly abnormal.Through further analysis,we demonstrated that Brgl is essential for maintaining the maintenance of cerebral cortical neural progenitors.Inactivation of Brg1 results in decreased cell proliferation,increased apoptosis,impaired normative differentiation of neural progenitors,destruction of apical junctional complexes,and loss of hippocampus in the cerebral cortex.We also found the ectopic deposition of neurons at the lateral ventricle in Brgl knockout mice,which is very similar to the periventricular heterotopia,a disease of malformations of the cerebral cortex in humans.This study explored the role of Brg1 in the early development of the cerebral cortex,which can help people understand the function of Brg1 in the development of cerebral cortex more deeply at the cellular and molecular level,and provide a theoretical basis for further study of mammalian nervous system development.In addition,the research results can provide an important theoretical basis for the study of the functional effects of Brg1 and the formation and exploratory treatment of cerebral cortex related diseases.
Keywords/Search Tags:cerebral cortex, Brg1, neural progenitors, malformations of the cerebral cortex
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