MiR-124 is differentially expressed in derivatives of the sympathoadrenal cell lineage and promotes neurite elongation in chromaffin cells.
The neural-crest-derived sympathoadrenal cell lineage gives rise to sympathetic neurons and to endocrine chromaffin cells of the adrenal medulla. Both cell types express a largely overlapping set of genes, including those coding for the molecular machinery related to the synthesis and exocytotic release of catecholamines. During their early development, sympathetic neurons and chromaffin cells rely on a shared transcription factor network that controls the establishment of these common features. Despite many similarities, mature sympathetic neurons and chromaffin cells significantly differ regarding their morphology and function. Most prominently, sympathetic neurons possess axons that are absent in mammalian adrenal chromaffin cells. The molecular mechanism underlying the divergent development of sympathoadrenal cells into neuronal and endocrine cells remains elusive. Mutational inactivation of the ribonuclease dicer hints at the importance of microRNAs in this diversification. We show here that miR-124 is detectable in developing sympathetic neurons but absent in chromaffin cell precursors. We further demonstrate that miR-124 promotes neurite elongation when transfected into cultured chromaffin cells indicating its capability to support the establishment of a neuronal morphology in non-neuronal sympathoadrenal cells. Our results also show that treatment of PC12 cells with the neurotrophin nerve growth factor leads to an upregulation of miR-124 expression and that inhibition of miR-124 reduces nerve-growth-factor-induced neurite outgrowth in PC12 cells. Thus, our data indicate that miR-124 contributes to the establishment of specific neuronal features in developing sympathoadrenal cells.
Institute of Anatomy and Cell Biology, Department of Molecular Embryology, Albert-Ludwigs-University, Albertstr. 17, 79104 Freiburg, Germany.
Stella
S
Shtukmaster
Institute of Anatomy and Cell Biology, Department of Molecular Embryology, Albert-Ludwigs-University, Albertstr. 17, 79104 Freiburg, Germany.
Priyanka
P
Narasimhan
Institute of Anatomy and Cell Biology, Department of Molecular Embryology, Albert-Ludwigs-University, Albertstr. 17, 79104 Freiburg, Germany.
Tehani
T
El Faitwri
Research Group Developmental Neurobiology, Max-Planck-Institute for Brain Research, Max-von-Laue-Strasse 4, 60438, Frankfurt/Main, Germany.|Institute of Clinical Neuroanatomy, Goethe University Frankfurt/M, Theodor-Stern-Kai 7, 60590, Frankfurt/M, Germany.
Jutta
J
Stubbusch
Research Group Developmental Neurobiology, Max-Planck-Institute for Brain Research, Max-von-Laue-Strasse 4, 60438, Frankfurt/Main, Germany.|Institute of Clinical Neuroanatomy, Goethe University Frankfurt/M, Theodor-Stern-Kai 7, 60590, Frankfurt/M, Germany.
Uwe
U
Ernsberger
Research Group Developmental Neurobiology, Max-Planck-Institute for Brain Research, Max-von-Laue-Strasse 4, 60438, Frankfurt/Main, Germany.|Institute of Clinical Neuroanatomy, Goethe University Frankfurt/M, Theodor-Stern-Kai 7, 60590, Frankfurt/M, Germany.
Hermann
H
Rohrer
Institute of Anatomy and Cell Biology, Department of Molecular Embryology, Albert-Ludwigs-University, Albertstr. 17, 79104 Freiburg, Germany.
Klaus
K
Unsicker
Institute of Anatomy and Cell Biology, Department of Molecular Embryology, Albert-Ludwigs-University, Albertstr. 17, 79104 Freiburg, Germany. katrin.huber@unfr.ch.|Department of Medicine, University of Fribourg, Route-Albert-Gockel 1, 1700, Fribourg, Switzerland. katrin.huber@unfr.ch.
Katrin
K
Huber
D000313:Adrenal Medulla / Q000166:cytology*; D000577:Amides / Q000494:pharmacology; D000818:Animals; D019070:Cell Lineage / Q000187:drug effects / Q000235:genetics*; D019439:Chromaffin Cells / Q000187:drug effects / Q000378:metabolism*; D020869:Gene Expression Profiling; D017403:In Situ Hybridization; D051379:Mice; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D009414:Nerve Growth Factors / Q000494:pharmacology; D016501:Neurites / Q000187:drug effects / Q000378:metabolism*; D016716:PC12 Cells; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D013564:Sympathetic Nervous System / Q000166:cytology*; D015854:Up-Regulation / Q000187:drug effects / Q000235:genetics
D000577:Amides; C548144:MIRN124 microRNA, rat; D035683:MicroRNAs; C540079:Mirn124 microRNA, mouse; D009414:Nerve Growth Factors; D047428:Protein Kinase Inhibitors; D011725:Pyridines; C108830:Y 27632
Chromaffin cell; Mouse; Sympathetic neuron; Sympathoadrenal cell lineage; miR-124