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Forschungsdatenbank PMU-SQQUID

Neuronal precursor-specific activity of a human doublecortin regulatory sequence.
Karl, C; Couillard-Despres, S; Prang, P; Munding, M; Kilb, W; Brigadski, T; Plötz, S; Mages, W; Luhmann, H; Winkler, J; Bogdahn, U; Aigner, L;
J Neurochem. 2005; 92(2):264-282
Originalarbeiten (Zeitschrift)

PMU-Autor/inn/en

Aigner Ludwig
Couillard-Després Sébastien

Abstract

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 beta-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.


Useful keywords (using NLM MeSH Indexing)

5" Flanking Region/genetics

Animals

Base Sequence

Blotting, Western

Brain/cytology

Brain/embryology

Brain/metabolism

Cell Lineage/genetics

Cells, Cultured

Gene Expression Regulation/drug effects

Growth Substances/pharmacology

Hippocampus/cytology

Humans

Mice

Mice, Inbred C57BL

Microtubule-Associated Proteins/biosynthesis

Microtubule-Associated Proteins/genetics*

Molecular Sequence Data

Neurons/metabolism*

Neuropeptides/biosynthesis

Neuropeptides/genetics*

Regulatory Sequences, Nucleic Acid/drug effects

Regulatory Sequences, Nucleic Acid/genetics*

Sequence Analysis, DNA

Sequence Deletion

Stem Cells/drug effects

Stem Cells/metabolism*

Transfection


Find related publications in this database (Keywords)

gene regulation
neurogenesis
neuronal migration
neuronal progenitors
transcription factors