Evidence for motoneuron lineage-specific regulation of Olig2 in the vertebrate neural tube.
Within the motoneuron precursor (pMN) domain of the developing spinal cord, the bHLH transcription factor, Olig2, plays critical roles in pattern formation and the generation of motor neuron and oligodendrocyte precursors. How are the multiple functions of Olig2 regulated? We have isolated a large BAC clone encompassing the human OLIG2 locus that rescues motor neuron and oligodendrocyte development but not normal pattern formation in Olig2(-/-) embryos. Within the BAC clone, we identified a conserved 3.6 kb enhancer sub-region that directs reporter expression specifically in the motor neuron lineage but not oligodendrocyte lineage in vivo. Our findings indicate complex regulation of Olig2 by stage- and lineage-specific regulatory elements. They further suggest that transcriptional regulation of Olig2 is involved in segregation of pMN neuroblasts.
Sun
Tao
T
Department of Pediatric Oncology, Dana-Farber Cancer Institute and Harvard Medical School, 44 Binney Street, Boston, MA 02115, USA. tas2009@med.cornell.edu
Hafler
Brian P
BP
Kaing
Sovann
S
Kitada
Masaaki
M
Ligon
Keith L
KL
Widlund
Hans R
HR
Yuk
Dong-In
DI
Stiles
Charles D
CD
Rowitch
David H
DH
D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000096:biosynthesis* / Q000172:deficiency / Q000235:genetics; D002454:Cell Differentiation / Q000235:genetics / Q000502:physiology; D019070:Cell Lineage / Q000235:genetics / Q000502:physiology*; D022202:Chromosomes, Artificial, Bacterial; D004742:Enhancer Elements, Genetic; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009046:Motor Neurons / Q000166:cytology / Q000502:physiology*; D009419:Nerve Tissue Proteins / Q000096:biosynthesis* / Q000172:deficiency / Q000235:genetics; D000076104:Oligodendrocyte Transcription Factor 2; D009836:Oligodendroglia / Q000166:cytology / Q000378:metabolism; D013116:Spinal Cord / Q000166:cytology* / Q000196:embryology*; D013234:Stem Cells / Q000166:cytology / Q000502:physiology
D051792:Basic Helix-Loop-Helix Proteins; D009419:Nerve Tissue Proteins; D000076104:Oligodendrocyte Transcription Factor 2; C405708:OLIG2 protein, human; C512773:Olig2 protein, mouse