A Dicer-miR-107 Interaction Regulates Biogenesis of Specific miRNAs Crucial for Neurogenesis

Abstract

Dicer controls the biogenesis of microRNAs (miRNAs) and is essential for neurogenesis. Recent reports show that the levels and substrate selectivity of DICER result in the preferential biogenesis of specific miRNAs in vitro. However, how dicer expression levels and miRNA biogenesis are regulated in vivo and how this affects neurogenesis is incompletely understood. Here we show that during zebrafish hindbrain development dicer expression levels are controlled by miR-107 to tune the biogenesis of specific miRNAs, such as miR-9, whose levels regulate neurogenesis. Loss of miR-107 function stabilizes dicer levels and miR-9 biogenesis across the ventricular hindbrain zone, resulting in an increase of both proliferating progenitors and postmitotic neurons. miR-9 ectopic accumulation in differentiating neuronal cells recapitulated the excessive neurogenesis phenotype. We propose that miR-107 modulation of dicer levels in differentiating neuronal cells is required to maintain the homeostatic levels of specific miRNAs, whose precise accumulation is essential for neurogenesis.

MicroRNAs in neural development: from master regulators to fine-tuners

“…This results in global downregulation of mature miRNAs, with miR-9 showing the strongest response to increased miR-107 activity. In situ hybridization studies have further revealed that the localization of miR-107 and Dicer is mutually exclusive along the hindbrain ventricular zone, thereby determining the border between the progenitor pool and differentiated neurons (Ristori et al, 2015).…”

“…Furthermore, TLX negatively regulates miR-9 expression levels, pointing to sophisticated feedback mechanisms that precisely control the balance between neural stem cell renewal and differentiation . To further complicate matters, miR-9 levels are also regulated by another miRNA, miR-107 (Ristori et al, 2015). Indeed, in the zebrafish MHB, miR-107 directly inhibits expression of the miRNA processing factor Dicer.…”

Epigenetics: major regulators of embryonic neurogenesis

“…So, we only focus on the latest research progress in the role of miRNA in neurogenesis. Recently, Ristori et al [132] show that miR-107 modulates the expression of Dicer and also interacts with Dicer during zebrafish hindbrain development. The miR-107-dicer interaction is indispensable for the specific accumulation of miR-9, which is crucial to neurogenesis [131,132].…”

“…Recently, Ristori et al [132] show that miR-107 modulates the expression of Dicer and also interacts with Dicer during zebrafish hindbrain development. The miR-107-dicer interaction is indispensable for the specific accumulation of miR-9, which is crucial to neurogenesis [131,132]. Furthermore, miRNAs can also interplay with other epigenetic regulators and play a comprehensive role in regulating neurogenesis [133].…”

Isolation and Culture of Adult Zebrafish Brain-derived Neurospheres

“…Here we describe a neurosphere-forming assay to demonstrate the role of miR-107 during zebrafish neurogenesis 11 . The protocol enables: 1) the collection of adult neural stem/progenitor cells either from zebrafish whole brain or from several dissected brain regions such as the telencephalon, the tectum, and the cerebellum; 2) the generation of floating and self-renewing neurospheres from adult neural stem/progenitor cells; 3) the down- and up-regulation of the expression of coding genes or small non-coding RNAs 11 in neurospheres, in order to investigate their roles in the proliferation and differentiation of neural stem/progenitor cells.…”