Upregulation of the HLH Id gene family in neural progenitors and glial cells of the rat spinal cord following contusion injury.
Spinal cord injury (SCI) leads to a complex sequence of cellular responses, including astrocyte activation, oligodendrocyte death, and ependymal cell proliferation. Inhibitors of DNA binding (Id1, Id2, Id3) belong to a helix-loop-helix (HLH) gene family. Id genes have been implicated in playing a vital role in the proliferation of many cell types, including astrocytes and myoblasts. In the present study, the expression of Id family members in spinal cord after contusion injury was investigated by in situ hybridization. Id1, Id2, and Id3 mRNA expression was upregulated 5 mm rostral and caudal to the lesion center, and reached maximal levels 3 days after SCI. In addition, cell populations expressing Id1, Id2, and Id3 mRNA were maximally increased 3 days after SCI. The increase in Id2 and Id3 mRNA expression and Id2 and Id3 mRNA+ cells was still observed at 8 days. The Id mRNA expressing cells were phenotyped by combining immunostaining of cell-specific markers with in situ hybridization. Glial fibrillary acidic protein (GFAP)+ astrocytes were found to express all three Id mRNA, whereas S-100alpha+ astrocytes only expressed high levels of Id2 and Id3 mRNA. Cells having a neural progenitor morphology and the marker nestin appeared after SCI and they expressed Id1, Id2, and Id3 mRNA. Interestingly, some Rip+ oligodendrocytes located in the areas close to the central canal expressed Id3 mRNA after injury. In conclusion, Id genes are upregulated in a time-dependent manner in astrocytes, oligodendrocytes, and neural progenitor subpopulations after SCI, suggesting that they play major roles in cellular responses following SCI.
Tzeng
S F
SF
Department of Neurobiology, Mental Retardation Research Center, UCLA School of Medicine, 760 Westwood Plaza, Los Angeles, CA 90024-1759, USA.
Bresnahan
J C
JC
Beattie
M S
MS
de Vellis
J
J
D000818:Animals; D000911:Antibodies, Monoclonal; D001253:Astrocytes / Q000378:metabolism; D002455:Cell Division / Q000502:physiology; D004268:DNA-Binding Proteins / Q000235:genetics*; D004195:Disease Models, Animal; D005786:Gene Expression Regulation / Q000502:physiology; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D018257:Helix-Loop-Helix Motifs / Q000235:genetics; D007150:Immunohistochemistry; D051798:Inhibitor of Differentiation Protein 1; D051797:Inhibitor of Differentiation Protein 2; D051796:Inhibitor of Differentiation Proteins; D007381:Intermediate Filament Proteins / Q000378:metabolism; D008297:Male; D009363:Neoplasm Proteins; D009419:Nerve Tissue Proteins; D064231:Nestin; D009457:Neuroglia / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism*; D009836:Oligodendroglia / Q000378:metabolism; D010641:Phenotype; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D020318:Rats, Long-Evans; D012097:Repressor Proteins; D009418:S100 Proteins / Q000378:metabolism; D013116:Spinal Cord / Q000378:metabolism* / Q000503:physiopathology; D013119:Spinal Cord Injuries / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D013234:Stem Cells / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics*; D015854:Up-Regulation / Q000235:genetics*
D000911:Antibodies, Monoclonal; D004268:DNA-Binding Proteins; D005904:Glial Fibrillary Acidic Protein; C497454:ID1 protein, rat; C497451:Id2 protein, rat; D051798:Inhibitor of Differentiation Protein 1; D051797:Inhibitor of Differentiation Protein 2; D051796:Inhibitor of Differentiation Proteins; D007381:Intermediate Filament Proteins; C577484:NES protein, human; D009363:Neoplasm Proteins; D009419:Nerve Tissue Proteins; C577486:Nes protein, rat; D064231:Nestin; D012333:RNA, Messenger; D012097:Repressor Proteins; D009418:S100 Proteins; D014157:Transcription Factors; C075640:ID3 protein, human