ena-STUDY-UNIVERSITY OF HAMBURG-07-08-2020-07:18:46:161-2277
Brahma-related gene 1 has time-specific roles during brain and eye development
During neural development, gene expression is tightly controlled to facilitate the generation of the diverse cell types, which make up the central nervous system. Brahma-related gene 1 (Brg1) is the catalytic subunit of the SWItch/sucrose nonfermentable (SWI/SNF) chromatin remodeling complex that regulates transcription. We investigated the role of Brg1 between embryonic day 6.5 (E6.5) and E14.5 in Sox2 positive neural stem cells. Being without major consequences at E6.5 and E14.5, loss of Brg1 between E7.5 and E12.5 resulted in severe morphological alterations including rosette-like structures in the subventricular zone and transdifferentiation of retinal pigment epithelium to neural retina. Brg1 deficient cells showed a decreased survival in vitro and in vivo. Furthermore, transcriptome analysis uncovered distinct changes in gene expression upon Brg1 loss pointing towards impaired neuron functions and composition of the extracellular matrix. Comparison with mice deficient of Integrase interactor 1 (Ini1) revealed that some of these alterations were Brg1 specific and not caused by a general dysfunction of the SWI/SNF complex. Together, these results suggest a critical role of Brg1 in neural stem cells regarding brain and eye development.
During neural development, gene expression is tightly controlled to facilitate the generation of the diverse cell types, which make up the central nervous system. Brahma-related gene 1 (Brg1) is the catalytic subunit of the SWItch/sucrose nonfermentable (SWI/SNF) chromatin remodeling complex that regulates transcription. We investigated the role of Brg1 between embryonic day 6.5 (E6.5) and E14.5 in Sox2 positive neural stem cells. Being without major consequences at E6.5 and E14.5, loss of Brg1 between E7.5 and E12.5 resulted in severe morphological alterations including rosette-like structures in the subventricular zone and transdifferentiation of retinal pigment epithelium to neural retina. Brg1 deficient cells showed a decreased survival in vitro and in vivo. Furthermore, transcriptome analysis uncovered distinct changes in gene expression upon Brg1 loss pointing towards impaired neuron functions and composition of the extracellular matrix. Comparison with mice deficient of Integrase interactor 1 (Ini1) revealed that some of these alterations were Brg1 specific and not caused by a general dysfunction of the SWI/SNF complex. Together, these results suggest a critical role of Brg1 in neural stem cells regarding brain and eye development.