Transcriptional perturbations by long noncoding RNAs with distinct spatio-temporal expression in the mammalian brain

Long noncoding RNAs (lncRNAs) have been implicated in numerous cellular processes including brain development. Yet the in vivo expression dynamics and molecular pathways regulated by these molecules are less well understood. Here, we leveraged a cohort of 13 lncRNA null-mutant mouse models to investigate the spatio-temporal expression of lncRNAs in the developing and adult brain. We observed a wide range of different spatio-temporal expression profiles in the brain. Several lncRNAs are differentially expressed both in time and space, and others present highly restricted expression in only selected brain regions. We further explore the consequent transcriptome alterations after loss of these lncRNA loci, and demonstrate altered regulation of a large variety of cellular pathways and processes. We further found that 6/13 lncRNA null-mutant strains significantly affect the expression of several neighboring protein-coding genes, in a cis-like manner. This resource provides insight into the expression patterns and potential effect of lncRNA loci in the developing and adult mammalian brain, and allows future examination of the specific functional relevance of these genes in neural development, brain function, and disease. We have sequenced wildtype and mutant whole brains from a cohort of 13 lncRNA knockout mouse strains at two developmetal timepoints (E14.5 and adult). Overall design: Comparison between wildtype and mutant whole brains transcriptomes in 13 lncRNA mutant strains at two different timepoints. Please note that for each knockout strain there are KO_E14.5 and KO_Adult samples, however for WT, each KO strain was compared to a cohort of 14 WTs (N3 background) and 3 WTs (N2.5 background) at either Adult or E14.5 timepoint. So in total there are 14 WT_Adult and 14 WT_E14.5 and in each differential analysis the 2 or 3 KOs (in N3 background) were compared to this entire cohort at the respective timepoint; a cohort of 3 WT_adult (N2.5) or 3 WT_E14.5 samples compared to other N2.5 KO samples at the respective timepoint. Thus, each processed data file was generated by comparing each KO strain to a cohort of WTs (at either Adult or E14.5 timepoint; ko_vs_WT_Adult or ko_vs_WT_embryonic). The mouse strain (background) used in these experiments a cross between 129 and C57BL/6 in the third generation (N3) of breeding in the C57BL/6 line, with the exception of the KANTR mice, which are N2.5.

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Goff LA, Groff AF, Sauvageau M, Trayes-Gibson Z, Sanchez-Gomez DB, Morse M, Martin RD, Elcavage LE, Liapis SC, Gonzalez-Celeiro M, Plana O, Li E, Gerhardinger C, Tomassy GS, Arlotta P, Rinn JL