| Abstract No.: | A-A1016 |
| Country: | USA |
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| Title: | CUX2 (CUTL2) INTEGRATES NOTCH AND BMP SIGNALING IN NEURAL PROGENITORS TO PROMOTE NEUROBLAST FORMATION |
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| Authors/Affiliations: | 1 Angelo Iulianella*; 2 Madhulika Sharma; 2 Greg Vanden Heuvel; 1 Paul Trainor; 3 Patrick Poirier, 3 Christiane Kalliny, 3 Yukiori Goto
1 Stowers Institute for Medical Research, Kansas, USA; 2 University of Kansas, Medical Center, USA; 3 McGill University, Montreal, QC, Canada
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| Content: | Objectives: Neurogenesis requires the coordination of neural progenitor proliferation and differentiation with cell cycle regulation. However, the mechanisms coordinating these distinct cellular activities are poorly understood. We examined the role of the transcription factor a Cut-like homeodomain transcription Cux2 (Cutl2) in cell cycle progression and neurogenesis in the spinal cord.
Materials and Methods: We employed both mutagenic and gain-of-function approaches in the mouse to address the role of Cux2 in spinal cord progenitor cells. We also supplemented transgenesis assays with in vivo electroporation to identify the pathways that regulate Cux2 function in spinal cord neural progenitors.
Results: Cux2 is dynamically expressed in the murine embryonic spinal and is a novel regulator of neural progenitor differentiation. Cux2 loss-of-function mouse mutants exhibited diminished Neurod and p27Kip1 activity and deficits in neuroblast and interneuron development. Conversely, in gain-of-function transgenic mice, Cux2 cell-autonomously induced high levels of Neurod and p27Kip1 and consequently enhanced neuroblast formation and neuronal differentiation, particularly with respect to interneurons. Sequential pulse labeling with IDU and BrdU revealed a role for Cux2 activity promoting cell cycle progression of neural progenitors. Interestingly, both Notch and BMP signaling coordinately regulate Cux2 expression in dividing basal progenitors that subsequently activate the neurogenic program and promote interneuron development.
Conclusions: Cux2 is a Notch and BMP target gene required for neuroblast formation and cell cycle exit in the murine spinal cord. Additionally, Cux2 controls the balance of interneuron and motoneurons in the developing spinal cord. These findings identify a key regulator of neural progenitors and reveal that Cux2 is a novel integrator Notch and BMP signaling in neural progenitors.
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