MicroRNA-124 Is a Subventricular Zone Neuronal Fate Determinant

Åkerblom, Malin; Sachdeva, Rohit; Barde, Isabelle; Verp, Sonia; Gentner, Bernhard; Trono, Didier; Jakobsson, Johan

doi:10.1523/jneurosci.0558-12.2012

Cited by 188 publications

(182 citation statements)

References 38 publications

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“…We have recently demonstrated that the generation of sensor mice using miRregulated vectors and lentiviral transgenesis is an efficient and reliable technique to monitor miRNA activity in the brain 14 . This approach has several advantages, including easy colabelling with other immunohistochemical markers, which otherwise is complicated when using alternative miRNA visualizing techniques such as in situ hybridization (ISH) 15 .…”

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confidence: 99%

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Visualization and genetic modification of resident brain microglia using lentiviral vectors regulated by microRNA-9

et al. 2013

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Functional studies of resident microglia require molecular tools for their genetic manipulation. Here we show that microRNA-9-regulated lentiviral vectors can be used for the targeted genetic modification of resident microglia in the rodent brain. Using transgenic reporter mice, we demonstrate that murine microglia lack microRNA-9 activity, whereas most other cells in the brain express microRNA-9. Injection of microRNA-9-regulated vectors into the adult rat brain induces transgene expression specifically in cells with morphological features typical of ramified microglia. The majority of transgene-expressing cells colabels with the microglia marker Iba1. We use this approach to visualize and isolate activated resident microglia without affecting circulating and infiltrating monocytes or macrophages in an excitotoxic lesion model in rat striatum. The microRNA-9-regulated vectors described here are a straightforward and powerful tool that facilitates functional studies of resident microglia.

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confidence: 99%

“…In all analysed mice (n420) we found reliable GFP expression and there were no differences in the pattern of GFP expression between mice. As a control we used LV.GFP mice, which have been previously characterized 14 .…”

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Visualization and genetic modification of resident brain microglia using lentiviral vectors regulated by microRNA-9

et al. 2013

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“…Several miRNAs are known to be associated with the nervous system, of which miR-124 is by far the most abundantly expressed (Kosik 2009;Lagos-Quintana et al 2002). Although several studies have suggested important roles of miR-124 in various aspects of neural development, including neurogenesis, neuronal differentiation and neurite outgrowth (Åkerblom et al 2012, Cheng et al 2009, Yu et al 2008, its physiological significance has remained controversial to date, since others have doubted its essential function in neural development (Cao et al 2007). However, several direct miR-124 targets have been identified that possibly account for its putative role in neural development, including the small GTPase Rho kinase Rock1.…”

Section: Discussionmentioning

confidence: 99%

“…Results from mice carrying conditional null mutations for dicer, an enzyme required for the cleavage of pre-miRs into mature miRs (Bernstein et al 2001), indicate the essential role of miRNAs in many cellular processes (Cuellar et al 2008;Davis et al 2011;Harris et al 2006;Harfe et al 2005;Nagalakshmi et al 2011). MicroRNAs are believed to contribute to the specification and differentiation of various cell types including neurons (Åkerblom et al 2012;Yu et al 2008;Stappert et al 2013). …”

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confidence: 99%

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MiR-124 is differentially expressed in derivatives of the sympathoadrenal cell lineage and promotes neurite elongation in chromaffin cells

Shtukmaster¹,

Narasimhan²,

Faitwri³

et al. 2016

Cell Tissue Res

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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-growthfactor-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.

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