PBX1 is required for adult subventricular zone neurogenesis

Britta Moyo Grebbin, Ann Christin Hau, Anja Groß, Marie Anders-Maurer, Jasmine Schramm, Matthew Koss, Christoph Wille, Michel Mittelbronn, Licia Selleri, Dorothea Schulte*

*Corresponding author for this work

Research output: Contribution to journalArticleResearchpeer-review

32 Citations (Scopus)


TALE-homeodomain proteins function as components of heteromeric complexes that contain one member each of the PBC and MEIS/ PREP subclasses. We recently showed that 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) has not been investigated. Using a genetic loss-of-function mouse 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 background, by contrast, severely compromised cell survival. By chromatin immunoprecipitation from endogenous tissues or isolated cells, we further detected PBX1binding 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 might act as a priming factor to mark these genes for subsequent activation. Collectively, our results establish that PBX1 regulates adult neural cell fate determination in a manner beyond that of its heterodimerization partner MEIS2.

Original languageEnglish
Pages (from-to)2281-2291
Number of pages11
JournalDevelopment (Cambridge)
Issue number13
Publication statusPublished - 1 Jul 2016


  • Adult neurogenesis
  • Cell fate specification
  • Doublecortin
  • Pioneer Factor
  • Subventricular zone
  • TALE-homeodomain protein


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