Independent regulatory elements in the nestin gene direct transgene expression to neural stem cells or muscle precursors.
Changes in intermediate filament gene expression occur at key steps in the differentiation of cell types in the mammalian CNS. Neuroepithelial stem cells express the intermediate filament protein nestin and down-regulate it sharply at the transition from proliferating stem cell to postmitotic neuron. Nestin is also expressed in muscle precursors but not in mature muscle cells. We show here that in transgenic mice, independent cell type-specific elements in the first and second introns of the nestin gene consistently direct reporter gene expression to developing muscle and neural precursors, respectively. The second intron contains an enhancer that functions in CNS stem cells, suggesting that there may be a single transcriptional mechanism regulating the CNS stem cell state. This enhancer is much less active in the PNS. The identification of these elements facilitates analysis of mechanisms controlling the switch in gene expression that occurs when muscle and brain precursors terminally differentiate.
Zimmerman
L
L
Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge 02139.
Parr
B
B
Lendahl
U
U
Cunningham
M
M
McKay
R
R
Gavin
B
B
Mann
J
J
Vassileva
G
G
McMahon
A
A
D000818:Animals; D001483:Base Sequence; D001921:Brain / Q000196:embryology / Q000378:metabolism; D002454:Cell Differentiation; D002490:Central Nervous System / Q000196:embryology / Q000378:metabolism; D017931:DNA Primers; D004622:Embryo, Mammalian / Q000502:physiology; D005314:Embryonic and Fetal Development; D004742:Enhancer Elements, Genetic; D004847:Epithelial Cells; D004848:Epithelium / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D007381:Intermediate Filament Proteins / Q000096:biosynthesis* / Q000235:genetics*; D007438:Introns; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D009132:Muscles / Q000196:embryology / Q000378:metabolism*; D009419:Nerve Tissue Proteins; D064231:Nestin; D009474:Neurons / Q000378:metabolism*; D010525:Peripheral Nerves / Q000196:embryology / Q000378:metabolism; D010957:Plasmids; D051381:Rats; D012045:Regulatory Sequences, Nucleic Acid; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism*
D017931:DNA Primers; D007381:Intermediate Filament Proteins; D009419:Nerve Tissue Proteins; C577485:Nes protein, mouse; C577486:Nes protein, rat; D064231:Nestin