Convergent microRNA actions coordinate neocortical development

Abstract

Neocortical development is a complex process that, at the cellular level, involves tight control of self-renewal, cell fate commitment, survival, differentiation and delamination/migration. These processes require, at the molecular level, the precise regulation of intrinsic signaling pathways and extrinsic factors with coordinated action in a spatially and temporally specific manner. Transcriptional regulation plays an important role during corticogenesis; however, microRNAs (miRNAs) are emerging as important post-transcriptional regulators of various aspects of central nervous system development. miRNAs are a class of small, single-stranded noncoding RNA molecules that control the expression of the majority of protein coding genes (i.e., targets). How do different miRNAs achieve precise control of gene networks during neocortical development? Here, we critically review all the miRNA–target interactions validated in vivo, with relevance to the generation and migration of pyramidal-projection glutamatergic neurons, and for the initial formation of cortical layers in the embryonic development of rodent neocortex. In particular, we focus on convergent miRNA actions, which are still a poorly understood layer of complexity in miRNA signaling, but potentially one of the keys to disclosing how miRNAs achieve the precise coordination of complex biological processes such as neocortical development.

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

“…We refer the reader to excellent recent reviews for a detailed discussion of miRNA function in adult neurogenesis (Luikart et al, 2012;Schouten et al, 2012) and focus our discussion here on embryonic neurogenesis -a period during which many miRNAs are enriched. Indeed, the global monitoring of miRNA expression during neurogenesis in vivo has identified timespecific (Barca-Mayo and De Pietri Tonelli, 2014;Lv et al, 2014;Miska et al, 2004;Nielsen et al, 2009;Yao et al, 2012), spatially restricted (ventral midline/midbrain dopaminergic progenitor pool) (Anderegg et al, 2013) or cell type-specific (Paridaen and Huttner, 2014;Ghosh et al, 2014) miRNAs, suggesting that different sets of miRNAs might be involved in neuronal versus glial differentiation. This is supported by the finding that 116 miRNAs (out of 351) are differentially expressed in primary cultures enriched for neurons, astrocytes, oligodendrocytes and microglia (Jovicic et al, 2013).…”

MicroRNAs in cancer: Glioblastoma and glioblastoma cancer stem cells

“…Through extensive molecular characterization of microRNA expression and function, it is clear that aberrantly expressed microRNAs have widespread effects on tumorigenesis, including on critical GBM pathways such as receptor tyrosine kinase signaling, p53 signaling, and cell cycle control (Ciafre et al, 2005; Kim et al, 2011; Papagiannakopoulos et al, 2008; Silber et al, 2012). However, the extent of microRNA dysregulation in GBM and emergence of many microRNA “families” suggest that single microRNAs may exert minimal effect and more global integrative approaches are needed to fully understand the role of microRNAs in GBM tumorigenesis and their therapeutic potential (Barca-Mayo and De Pietri Tonelli, 2014; Sun et al, 2012). Moving forward, it will be important for the facilitation of a timely transition from findings on high throughput analysis in the setting of GBM to thorough functional analyses.…”

Are microRNAs the Molecular Link Between Metabolic Syndrome and Alzheimer’s Disease?

“…Continuing with the example of SIRT1, the repression mediated by miR-34a could be reinforced by additional miRNAs [89] including the brain-enriched miR-132 [90] or the action of miR-9 in brain [91] and peripheral tissues [92]. The convergence of two or more co-expressed miRNAs on a given target normally results in an increased degree of translational repression [93,94].…”