Project description:The basal ganglia control multiple sensorimotor behaviors though anatomically segregated and topographically organized subcircuits with outputs to specific downstream circuits. However, it is unclear how the anatomical organization of basal ganglia output circuits relates to the molecular diversity of cell types. Here, we demonstrate that the major output nucleus of the basal ganglia, the substantia nigra pars reticulata (SNr) is comprised of transcriptomically distinct subclasses that reflect its distinct progenitor lineages. We show that these subclasses are topographically organized within SNr, project to distinct targets in the midbrain and hindbrain, and receive inputs from different striatal subregions. Finally, we show that these mouse subclasses are also identifiable in human SNr neurons, suggesting that the genetic organization of SNr is evolutionarily conserved. These findings provide a unifying logic for how the developmental specification of diverse SNr neurons relates to the anatomical organization of basal ganglia circuits controlling specialized downstream brain regions.
Project description:The basal ganglia control multiple sensorimotor behaviors though anatomically segregated and topographically organized subcircuits with outputs to specific downstream circuits. However, it is unclear how the anatomical organization of basal ganglia output circuits relates to the molecular diversity of cell types. Here, we demonstrate that the major output nucleus of the basal ganglia, the substantia nigra pars reticulata (SNr) is comprised of transcriptomically distinct subclasses that reflect its distinct progenitor lineages. We show that these subclasses are topographically organized within SNr, project to distinct targets in the midbrain and hindbrain, and receive inputs from different striatal subregions. Finally, we show that these mouse subclasses are also identifiable in human SNr neurons, suggesting that the genetic organization of SNr is evolutionarily conserved. These findings provide a unifying logic for how the developmental specification of diverse SNr neurons relates to the anatomical organization of basal ganglia circuits controlling specialized downstream brain regions.
Project description:The basal ganglia control multiple sensorimotor behaviors though anatomically segregated and topographically organized subcircuits with outputs to specific downstream circuits. However, it is unclear how the anatomical organization of basal ganglia output circuits relates to the molecular diversity of cell types. Here, we demonstrate that the major output nucleus of the basal ganglia, the substantia nigra pars reticulata (SNr) is comprised of transcriptomically distinct subclasses that reflect its distinct progenitor lineages. We show that these subclasses are topographically organized within SNr, project to distinct targets in the midbrain and hindbrain, and receive inputs from different striatal subregions. Finally, we show that these mouse subclasses are also identifiable in human SNr neurons, suggesting that the genetic organization of SNr is evolutionarily conserved. These findings provide a unifying logic for how the developmental specification of diverse SNr neurons relates to the anatomical organization of basal ganglia circuits controlling specialized downstream brain regions.
Project description:• Evolutionarily conserved SWI-SNF ATP-dependent chromatin remodeling complexes (CRCs) change nucleosome positioning and chromatin states, affecting gene expression to regulate important regulatory processes controlling such as proper development and hormonal signalling pathways. • In our study we used transcript profiling, chromatin immunoprecipitation (ChIP), exhaustive protein-protein interaction study including mass-spectrometry, yeast-two-hybrid and bimolecular fluorescence complementation (BiFC) along with hormone and metabolite profiling, and phenotype assessments to distinguish the functions of Arabidopsis SWP73A and SWP73B subunits in Arabidopsis. • We identified a novel subclass of SWI/SNF chromatin remodelling complexes defined by the presence of SWP73A subunit. Therefore, we propose a refined classification of SWI/SNF CRCs in Arabidopsis, introducing BAS-A (SWP73A-containing) and BAS-B (SWP73B-containing) subclasses. The SWP73A and SWP73B-carrying subclasses of SWI/SNF CRCs exhibit differential properties demonstrated by distinct chromatin binding patterns and divergent effect on hormone biosynthesis and metabolism. We found that SWP73A plays a specific role that cannot be fully compensated by SWP73B. We recognized that some atypical subclasses of SWI/SNF CRCs may be likely formed in mutant lines with inactivated SWP73 subunits. • Our study reveals that the duplication of the SWP73 subunit contributes to unique and shared functions of subclasses of SWI/SNF CRCs in the control of various regulatory processes in Arabidopsis.
Project description:Novel prognostic subclasses of high-grade astrocytoma are identified and discovered to resemble stages in neurogenesis. One tumor class displaying neuronal lineage markers shows longer survival, while two tumor classes enriched for neural stem cell markers display equally short survival. Poor prognosis subclasses exhibit either markers of proliferation or of angiogenesis and mesenchyme. Analysis of gene expression data is described in Phillips et al., Cancer Cell, 2006. Keywords: Disease state comparison