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Biology subjects

Moore, D.

Publications and source records attributed to Moore, D..

3 recordsLinked to original sources

Foxp1 controls neural stem cell competence and bias towards deep layer cortical fate.

SUMMARYThe laminar architecture of the mammalian neocortex depends on the orderly generation of distinct neuronal subtypes by apical radial glia (aRG) during embryogenesis. We identify critical roles for Foxp1 in maintaining RG identity and gating the temporal competency for early neurogenesis. High levels of Foxp1 are associated with early aRG and are required to promote proliferation and influence cell division symmetry, favoring aRG expansion and production of early born neurons. The potent pro-progenitor functions of Foxp1 are revealed through its ability to preserve a population of cells with aRG identity throughout development and extend the early neurogenic period into postnatal life. Foxp1 further promotes the formation of cells resembling basal RG (bRG), a progenitor group implicated in the increased size and complexity of the human cortex. Consistent with this role, we show that FOXP1 is associated with the initial formation and expansion of bRG during human corticogenesis.\n\nHIGHLIGHTSO_LIFoxp1 is transiently expressed by aRG during the early phase of corticogenesis\nC_LIO_LIFoxp1 promotes self-renewing vertical cell divisions and aRG maintenance\nC_LIO_LIFoxp1 gates the time window of deep layer neurogenesis\nC_LIO_LIEctopic Foxp1 expression can elicit bRG formation\nC_LI

developmental biology

Quantitative Real-Time Imaging of Glutathione with Sub-Cellular Resolution

Quantitative imaging of glutathione with high spatial and temporal resolution is essential for studying the roles of glutathione in redox biology. We developed a fluorescent glutathione probe--HaloRT--that targets organelles of interest through expressing organelle-specific HaloTag proteins. Using HaloRT, we quantitatively measure the glutathione concentrations in the nucleus and the cytosol and find no appreciable concentration gradient between these two organelles, challenging the view of nuclear compartmentalization of glutathione.

cell biology

DNA copy number gains of TCF4 (E2-2) are associated with poor outcome and the activated B-cell-like subtype of diffuse large B-cell lymphoma

The activated B-cell (ABC) subtype of diffuse large B-cell lymphoma (DLBCL) is characterized by the chronic activation of signaling initiated by immunoglobulin- (IgM). By analyzing DNA copy profiles of 1,000 DLBCLs, we identified gains of 18q21.2 as the most frequent genetic alteration in ABC-like DLBCL. We show that these alterations target the TCF4 (E2-2) transcription factor, and that over-expression of TCF4 leads to its occupancy on immunoglobulin gene enhancers and increased expression of IgM at the transcript and protein level. The TCF4 gene is one of the top BRD4-regulated genes in DLBCL. Using a BET proteolysis-targeting chimera (PROTAC) we show that TCF4 and IgM expression can be extinguished, and ABC-like DLBCL cells can be killed in vitro and in vivo. This highlights a novel genetic mechanism for promoting immunoglobulin signaling in ABC-like DLBCL and provides a functional rationale for the use of BET inhibitors in this disease.

genomics