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

Abstract

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.

From proliferation to target innervation: signaling molecules that direct sympathetic nervous system development

“…(Stubbusch, et al, 2013). One such microRNA, miRNA 124, is present in sympathetic mouse neuroblasts and causes neurite elongation when over-expressed in cultured chromaffin cells and is up-regulated during the induction of neurites by NGF in PC12 cells (Shtukmaster, et al, 2016).…”

miR-375 negatively regulates the synthesis and secretion of catecholamines by targeting Sp1 in rat adrenal medulla

“…Conversely, microRNA-24 (miR-24) significantly decreased aldosterone and cortisol production by directly targeting Cyp11b1 and Cyp11b2 mRNAs (35). However, only few studies have examined the expressions and functions of miRNAs in the adrenal medulla such as microRNA-221 (miR-221) (11) and mi-croRNA-124 (miR-124) (42), which have been reported to affect the differentiation and function of PC12 cells, which are derived from a rat adrenal medullary tumor (10).…”

MicroRNAs in neural crest development and neurocristopathies

“…In particular, the authors showed that miR-375 targets Sp1 , the regulator of TH and DBH, in response to stress [ 46 ]. Another study conducted by Shtukmaster and colleagues demonstrated that miR-124 is also expressed in developing sympathetic neurons and supports the maintenance of neuronal morphology in sympathoadrenal cells [ 47 ].…”