TALE-homeodomain proteins function as part of heteromeric complexes that contain one member each of the PBC- and MEIS/PREP-subclasses. As we have recently shown, MEIS2 cooperates with the neurogenic transcription factor PAX6 in the control of adult subventricular zone (SVZ) neurogenesis in rodents. Expression of the PBC-protein Pbx1 in the SVZ has been reported but its functional role(s) had not yet been investigated. Using a genetic loss-of-function model, we now show that Pbx1 is an early regulator of SVZ neurogenesis. Targeted deletion of Pbx1 by retroviral transduction of Cre recombinase into Pbx2-deficient SVZ stem- and progenitor cells carrying floxed alleles of Pbx1 significantly reduced the production of neurons and increased the generation of oligodendrocytes. Loss of Pbx1-expression in neuronally committed neuroblasts in the rostral migratory stream in a Pbx2 null (Pbx2−/−) background, by contrast, severely compromised cell survival. By chromatin immunoprecipitation from endogenous tissues or isolated cells, we further detect PBX1 binding to known regulatory regions of the neuron-specific genes DCX and TH days or even weeks before the respective genes are expressed during the normal program of SVZ neurogenesis, suggesting that PBX1 may act as priming factor to mark these genes for subsequent activation. Collectively, our results establish that PBX1 regulates adult neural cell fate determination in a way that goes beyond the that of its heterodimerization partner MEIS2.
Pbx1 is required for adult SVZ neurogenesis
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Britta Moyo Grebbin, Ann-Christin Hau, Anja Groß, Marie Anders-Maurer, Jasmine Schramm, Matthew Koss, Christoph Wille, Michel Mittelbronn, Licia Selleri, Dorothea Schulte; Pbx1 is required for adult SVZ neurogenesis. Development 2016; dev.128033. doi: https://doi.org/10.1242/dev.128033
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