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Neuronal precursor‐specific activity of a human doublecortin regulatory sequence
Author(s) -
Karl Claudia,
CouillardDespres Sebastien,
Prang Peter,
Munding Matthias,
Kilb Werner,
Brigadski Tanja,
Plötz Sonja,
Mages Wolfgang,
Luhmann Heiko,
Winkler Jürgen,
Bogdahn Ulrich,
Aigner Ludwig
Publication year - 2005
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2004.02879.x
Subject(s) - doublecortin , neurogenesis , biology , stathmin , reporter gene , microbiology and biotechnology , gene , microtubule associated protein , microtubule , gene expression , genetics , neuroscience , dentate gyrus , central nervous system
The doublecortin (DCX) gene encodes a 40‐kDa microtubule‐associated protein specifically expressed in neuronal precursors of the developing and adult CNS. Due to its specific expression pattern, attention was drawn to DCX as a marker for neuronal precursors and neurogenesis, thereby underscoring the importance of its promoter identification and promoter analysis. Here, we analysed the human DCX regulatory sequence and confined it to a 3.5‐kb fragment upstream of the ATG start codon. We demonstrate by transient transfection experiments that this fragment is sufficient and specific to drive expression of reporter genes in embryonic and adult neuronal precursors. The activity of this regulatory fragment overlapped with the expression of endogenous DCX and with the young neuronal markers class III β‐tubulin isotype and microtubule‐associated protein Map2ab but not with glial or oligodendroglial markers. Electrophysiological data further confirmed the immature neuronal nature of these cells. Deletions within the 3.5‐kb region demonstrated the relevance of specific regions containing transcription factor‐binding sites. Moreover, application of neurogenesis‐related growth factors in the neuronal precursor cultures suggested the lack of direct signalling of these factors on the DCX promoter construct.