The bHLH transcription factor Hand2 is essential for the maintenance of noradrenergic properties in differentiated sympathetic neurons
| Autor: | Kazuto Kobayashi, Mirko Schmidt, Uwe Ernsberger, Matthias Stanke, Hermann Rohrer, Marthe J. Howard, Manuela Pape, Shengyin Lin |
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| Jazyk: | angličtina |
| Rok vydání: | 2009 |
| Předmět: |
Male
Sympathetic Nervous System DBH Proliferation Dopamine beta-Hydroxylase Mice Norepinephrine 0302 clinical medicine Basic Helix-Loop-Helix Transcription Factors RNA Small Interfering siRNA knockdown Neurons 0303 health sciences Gene knockdown biology Reverse Transcriptase Polymerase Chain Reaction Cell Differentiation Choline acetyltransferase Immunohistochemistry Sympathetic ganglia medicine.anatomical_structure VAChT Gene Knockdown Techniques embryonic structures TH Female HAND2 medicine.drug animal structures Tyrosine 3-Monooxygenase Hand2 Sympathetic neuron survival Article 03 medical and health sciences Vesicular acetylcholine transporter medicine Animals Molecular Biology 030304 developmental biology DNA Primers Tyrosine hydroxylase Base Sequence Epistasis Genetic Cell Biology Molecular biology ChAT biology.protein Cholinergic Neuron 030217 neurology & neurosurgery Developmental Biology |
| Popis: | The basic helix–loop–helix transcription factor Hand2 is essential for the proliferation and noradrenergic differentiation of sympathetic neuron precursors during development. Here we address the function of Hand2 in postmitotic, differentiated sympathetic neurons. Knockdown of endogenous Hand2 in cultured E12 chick sympathetic neurons by siRNA results in a significant (about 60%) decrease in the expression of the noradrenergic marker genes dopamine-β-hydroxylase (DBH) and tyrosine hydroxylase (TH). In contrast, expression of the pan-neuronal genes TuJ1, HuC and SCG10 was not affected. To analyze the in vivo role of Hand2 in differentiated sympathetic neurons we used mice harboring a conditional Hand2-null allele and excised the gene by expression of Cre recombinase under control of the DBH promotor. Mouse embryos homozygous for Hand2 gene deletion showed decreased sympathetic neuron number and TH expression was strongly reduced in the residual neuron population. The in vitro Hand2 knockdown also enhances the CNTF-induced expression of the cholinergic marker genes vesicular acetylcholine transporter (VAChT) and choline acetyltransferase (ChAT). Taken together, these findings demonstrate that the Hand2 transcription factor plays a key role in maintaining noradrenergic properties in differentiated neurons. |
| Databáze: | OpenAIRE |
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