TY - JOUR
T1 - Histone deacetylase 1 is essential for oligodendrocyte specification in the zebrafish CNS
AU - Cunliffe, Vincent T.
AU - Casaccia-Bonnefil, Patrizia
N1 - Funding Information:
We are grateful to Professor P.W. Ingham for support and encouragement, sharing mutant stocks and facilities, and for critical reading of the manuscript; to F. Browne, L. Gleadall and M. Green for fish care, and to Dr C. Brösamle (Carnegie Insititution, Baltimore, USA), Dr T. Whitfield, C. Parkin and R. Kim for sharing plasmid DNA stocks. This work was funded in part by a Centre Development Grant from the UK Medical Research Council. Research in the laboratory of V.T.C. is supported by the MRC and the Spastic Paraplegia Foundation. Research in the laboratory of P.C-B. is supported by grants from NIH-NINDS (RO1-NS42925) and from the National Multiple Sclerosis Society (RG3421-A-4 and PP1053).
PY - 2006/1
Y1 - 2006/1
N2 - Histone deacetylases are critical components of transcriptional silencing mechanisms that regulate embryonic development. Recent work has shown that histone deacetylase 1 (hdac1) is required for neuronal specification during zebrafish CNS development. We show here that specification of oligodendrocytes, the myelinating cells of the CNS, also fails to occur in the hdac1 mutant hindbrain, but persistence of neural progenitors in the hindbrain ventricular zone, which express pax6a and sox2, is independent of hdac1 activity. Commitment of ventral neural progenitors to the oligodendrocyte fate is thought to require co-ordinate, hedgehog-dependent expression of olig2 and nkx2.2a in these cells, leading to expression of sox10 and subsequent differentiation of oligodendrocytes. Remarkably, transcription of olig2 is extinguished in ventral neural progenitors of the hdac1 mutant hindbrain, whereas expression of nkx2.2a is up-regulated in these cells, and sox10 expression is suppressed. Our results identify hdac1 as a novel, essential component of the mechanism that allocates neural progenitors to the oligodendrocyte fate, by attenuating expression of a subset of neural progenitor genes and rendering olig2 expression responsive to Hedgehog signalling.
AB - Histone deacetylases are critical components of transcriptional silencing mechanisms that regulate embryonic development. Recent work has shown that histone deacetylase 1 (hdac1) is required for neuronal specification during zebrafish CNS development. We show here that specification of oligodendrocytes, the myelinating cells of the CNS, also fails to occur in the hdac1 mutant hindbrain, but persistence of neural progenitors in the hindbrain ventricular zone, which express pax6a and sox2, is independent of hdac1 activity. Commitment of ventral neural progenitors to the oligodendrocyte fate is thought to require co-ordinate, hedgehog-dependent expression of olig2 and nkx2.2a in these cells, leading to expression of sox10 and subsequent differentiation of oligodendrocytes. Remarkably, transcription of olig2 is extinguished in ventral neural progenitors of the hdac1 mutant hindbrain, whereas expression of nkx2.2a is up-regulated in these cells, and sox10 expression is suppressed. Our results identify hdac1 as a novel, essential component of the mechanism that allocates neural progenitors to the oligodendrocyte fate, by attenuating expression of a subset of neural progenitor genes and rendering olig2 expression responsive to Hedgehog signalling.
KW - Hedgehog
KW - Histone deacetylase
KW - Oligodendrocyte
KW - Zebrafish
KW - nkx2.2a
KW - olig2
UR - http://www.scopus.com/inward/record.url?scp=29744438031&partnerID=8YFLogxK
U2 - 10.1016/j.mod.2005.10.005
DO - 10.1016/j.mod.2005.10.005
M3 - Article
C2 - 16324829
AN - SCOPUS:29744438031
SN - 0925-4773
VL - 123
SP - 24
EP - 30
JO - Mechanisms of Development
JF - Mechanisms of Development
IS - 1
ER -