title: Understanding the role of dicer in astrocyte development.
abstract: The Dicer1 allele is used to show that microRNAs (miRNAs) play important roles in astrocyte development and functions. While it is known that astrocytes that lack miRNAs are dysregulated, the in vivo phenotypes of these astrocytes are not well understood. In this study, we use Aldh1l1-EGFP transgene, a marker of astrocytes, to characterize mouse models with conditional Dicer1 ablation (via either human or mouse GFAP-Cre). This transgene revealed novel features of the defective astrocytes from the absence of miRNA. Although astrocyte miRNAs were depleted in both lines, we found histological and molecular differences in the Aldh1l1-EGFP cells between the two Cre lines. Aldh1l1-EGFP cells from hGFAP-Cre mutant lines displayed up-regulation of Aldh1l1-EGFP with increased proliferation and a genomic profile that acquired many features of wildtype primary astrocyte cultures. In the young mGFAP-Cre mutant lines we found that Aldh1l1-EGFP cells were disorganized and hyperproliferative in the developing cerebellum. Using the Aldh1l1-EGFP transgene, our work provides new insights into the roles of miRNAs in astrocyte development and the features of astrocytes in these two mouse models.
authors.affiliation: Department of Neurology, University of California San Francisco, San Francisco, California, United States of America.
authors.forename: Shen-Yi Bruce
authors.initials: SY
authors.lastname: Howng
authors.affiliation: Department of Neurology, University of California San Francisco, San Francisco, California, United States of America; Howard Hughes Medical Institute, School of Medicine, San Francisco, California, United States of America.
authors.forename: Yong
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Department of Neurology, University of California San Francisco, San Francisco, California, United States of America; Howard Hughes Medical Institute, School of Medicine, San Francisco, California, United States of America.
authors.forename: Louis
authors.initials: L
authors.lastname: Ptáček
authors.affiliation: Department of Neurology, University of California San Francisco, San Francisco, California, United States of America.
authors.forename: Ying-Hui
authors.initials: YH
authors.lastname: Fu
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000166:cytology* / Q000378:metabolism*; D002478:Cells, Cultured; D002531:Cerebellum / Q000378:metabolism; D015870:Gene Expression; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D017930:Genes, Reporter; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D035683:MicroRNAs / Q000235:genetics; D009154:Mutation; D010641:Phenotype; D016548:Prosencephalon / Q000378:metabolism; D043244:Ribonuclease III / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D059467:Transcriptome
chemical_list: D035683:MicroRNAs; D043244:Ribonuclease III