HDAC1 and HDAC2 control the specification of neural crest cells into peripheral glia.
Schwann cells, the myelinating glia of the peripheral nervous system (PNS), originate from multipotent neural crest cells that also give rise to other cells, including neurons, melanocytes, chondrocytes, and smooth muscle cells. The transcription factor Sox10 is required for peripheral glia specification. However, all neural crest cells express Sox10 and the mechanisms directing neural crest cells into a specific lineage are poorly understood. We show here that histone deacetylases 1 and 2 (HDAC1/2) are essential for the specification of neural crest cells into Schwann cell precursors and satellite glia, which express the early determinants of their lineage myelin protein zero (P0) and/or fatty acid binding protein 7 (Fabp7). In neural crest cells, HDAC1/2 induced expression of the transcription factor Pax3 by binding and activating the Pax3 promoter. In turn, Pax3 was required to maintain high Sox10 levels and to trigger expression of Fabp7. In addition, HDAC1/2 were bound to the P0 promoter and activated P0 transcription. Consistently, in vivo genetic deletion of HDAC1/2 in mouse neural crest cells led to strongly decreased Sox10 expression, no detectable Pax3, virtually no satellite glia, and no Schwann cell precursors in dorsal root ganglia and peripheral nerves. Similarly, in vivo ablation of Pax3 in the mouse neural crest resulted in strongly reduced expression of Sox10 and Fabp7. Therefore, by controlling the expression of Pax3 and the concerted action of Pax3 and Sox10 on their target genes, HDAC1/2 direct the specification of neural crest cells into peripheral glia.
Institute of Molecular Health Sciences, Department of Biology, ETH Zurich, CH-8093 Zurich, Switzerland, FMI for Biomedical Research, Novartis Research Foundation, CH-4058 Basel, Switzerland, Institute of Anatomy, University of Zurich, CH-8057 Zurich, Switzerland, Institute of Zoology, Department of Biology, University of Fribourg, CH-1700 Fribourg, Switzerland, and Developmental Biology and Neonatal Medicine Program, H.B. Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, Indiana 46202.
Claire
C
Jacob
Pirmin
P
Lötscher
Stefanie
S
Engler
Arianna
A
Baggiolini
Sandra
S
Varum Tavares
Valérie
V
Brügger
Nessy
N
John
Stine
S
Büchmann-Møller
Paige L
PL
Snider
Simon J
SJ
Conway
Teppei
T
Yamaguchi
Patrick
P
Matthias
Lukas
L
Sommer
Ned
N
Mantei
Ueli
U
Suter
D000818:Animals; D002454:Cell Differentiation / Q000502:physiology*; D018507:Gene Expression Regulation, Developmental; D056284:Histone Deacetylase 1 / Q000235:genetics / Q000378:metabolism*; D056464:Histone Deacetylase 2 / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D009432:Neural Crest / Q000166:cytology / Q000378:metabolism*; D058953:Neural Stem Cells / Q000166:cytology / Q000378:metabolism*; D009836:Oligodendroglia / Q000166:cytology / Q000378:metabolism*; D000072041:PAX3 Transcription Factor; D051761:Paired Box Transcription Factors / Q000235:genetics / Q000378:metabolism; D055757:SOXE Transcription Factors / Q000235:genetics / Q000378:metabolism; D012583:Schwann Cells / Q000166:cytology / Q000378:metabolism*
D000072041:PAX3 Transcription Factor; D051761:Paired Box Transcription Factors; D055757:SOXE Transcription Factors; C527924:Sox10 protein, mouse; C068686:Pax3 protein, mouse; D056284:Histone Deacetylase 1; D056464:Histone Deacetylase 2
histone deacetylases; neural crest cells; peripheral glia specification; transcriptional control