The BAF complex interacts with Pax6 in adult neural progenitors to establish a neurogenic cross-regulatory transcriptional network.
Numerous transcriptional regulators of neurogenesis have been identified in the developing and adult brain, but how neurogenic fate is programmed at the epigenetic level remains poorly defined. Here, we report that the transcription factor Pax6 directly interacts with the Brg1-containing BAF complex in adult neural progenitors. Deletion of either Brg1 or Pax6 in the subependymal zone (SEZ) causes the progeny of adult neural stem cells to convert to the ependymal lineage within the SEZ while migrating neuroblasts convert to different glial lineages en route to or in the olfactory bulb (OB). Genome-wide analyses reveal that the majority of genes downregulated in the Brg1 null SEZ and OB contain Pax6 binding sites and are also downregulated in Pax6 null SEZ and OB. Downstream of the Pax6-BAF complex, we find that Sox11, Nfib, and Pou3f4 form a transcriptional cross-regulatory network that drives neurogenesis and can convert postnatal glia into neurons. Taken together, elements of our work identify a tripartite effector network activated by Pax6-BAF that programs neuronal fate.
Institute for Stem Cell Research, Helmholtz Centre Munich German Research Center for Environmental Health (GmbH), 85764 Neuherberg, Germany; Physiological Genomics, Medical Faculty, University of Munich, Schillerstrasse 46, 80633 Munich, Germany.
Jovica
J
Ninkovic
Andrea
A
Steiner-Mezzadri
Melanie
M
Jawerka
Umut
U
Akinci
Giacomo
G
Masserdotti
Stefania
S
Petricca
Judith
J
Fischer
Alexander
A
von Holst
Johanes
J
Beckers
Chichung D
CD
Lie
David
D
Petrik
Erik
E
Miller
Jiong
J
Tang
Jiang
J
Wu
Veronique
V
Lefebvre
Jeroen
J
Demmers
Amelia
A
Eisch
Daniel
D
Metzger
Gerald
G
Crabtree
Martin
M
Irmler
Raymond
R
Poot
Magdalena
M
Götz
D053687:Adult Stem Cells / Q000166:cytology / Q000378:metabolism*; D000818:Animals; D015536:Down-Regulation; D005136:Eye Proteins / Q000378:metabolism*; D053263:Gene Regulatory Networks; D018398:Homeodomain Proteins / Q000378:metabolism*; D051379:Mice; D058953:Neural Stem Cells / Q000166:cytology / Q000378:metabolism*; D009474:Neurons / Q000166:cytology* / Q000378:metabolism*; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors / Q000378:metabolism*; D012097:Repressor Proteins / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
D005136:Eye Proteins; D018398:Homeodomain Proteins; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors; C000605732:Pax6 protein, mouse; D012097:Repressor Proteins; C491090:Smarcc1 protein, mouse; D014157:Transcription Factors