Extracellular and intracellular regulation of oligodendrocyte development: roles of Sonic hedgehog and expression of E proteins.
Recent advances in understanding oligodendrocyte development have revealed the importance of both extra- and intracellular molecules in regulating the induction, survival, and proliferation of early oligodendrocyte progenitors. The signaling molecule Sonic hedgehog (Shh) is critical for normal development of oligodendrocytes, although the precise influences of Shh on cells of the oligodendrocyte lineage are unclear. The present study shows that Shh increased the number of oligodendrocyte precursors in both pure cultures of oligodendrocyte precursors and mixed cultures from embryonic rat spinal cord. In pure precursor cultures Shh increased cell survival. In mixed cultures, Shh increased both the survival and proliferation of oligodendrocyte precursors in a concentration dependent manner. One intracellular consequence of exposure to Shh is the activation of transcription factors in oligodendrocyte lineage cells, which are critical for oligodendrocyte development, helix-loop-helix (HLH) transcription factors, Olig1 and 2. In many cases, HLH proteins such as Olig1 and Olig2 heterodimerize with other HLH proteins, such as members of the E subfamily, which are critical regulators of cell proliferation and differentiation. Immature (A2B5(+)) and more mature (O4(+)) rat oligodendrocyte precursors in dissociated cell culture expressed Olig1 as well as E proteins, HEB and E2A. Similarly, cells bearing the morphology of oligodendrocyte precursors expressed both Olig1 and HEB or E2A. We propose that E2A and/or HEB, possibly in combination with Olig1 and 2, are critical components of oligodendrogenesis and may regulate cell survival, proliferation, and fate decisions in the oligodendrocyte lineage.
Sussman
Caroline R
CR
Department of Neurosciences, Case Western Reserve University School of Medicine, Cleveland, Ohio 44106-4975, USA. crs13@po.cwru.edu
Davies
Jeannette E
JE
Miller
Robert H
RH
D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins; D002450:Cell Communication / Q000187:drug effects / Q000502:physiology; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology*; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D019070:Cell Lineage / Q000187:drug effects / Q000502:physiology; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D002490:Central Nervous System / Q000166:cytology / Q000196:embryology* / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000187:drug effects / Q000378:metabolism; D005333:Fetus; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects / Q000502:physiology; D053823:Hedgehog Proteins; D007150:Immunohistochemistry; D009419:Nerve Tissue Proteins / Q000187:drug effects / Q000378:metabolism; D009836:Oligodendroglia / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D013234:Stem Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D015534:Trans-Activators / Q000378:metabolism* / Q000494:pharmacology; D014157:Transcription Factors / Q000187:drug effects / Q000378:metabolism*
D051792:Basic Helix-Loop-Helix Proteins; D004268:DNA-Binding Proteins; D053823:Hedgehog Proteins; D009419:Nerve Tissue Proteins; D015534:Trans-Activators; D014157:Transcription Factors; C498633:Olig1 protein, rat; C509239:SHH protein, human; C407909:TCF3 protein, human; C073366:TCF12 protein, human