Abstract
Left–right asymmetry in anatomical structures and functions of the nervous system is present throughout the animal kingdom. For example, language centers are localized in the left side of the human brain, while spatial recognition functions are found in the right hemisphere in the majority of the population. Disruption of asymmetry in the nervous system is correlated with neurological disorders. Although anatomical and functional asymmetries are observed in mammalian nervous systems, it has been a challenge to identify the molecular basis of these asymmetries. C. elegans has emerged as a prime model organism to investigate molecular asymmetries in the nervous system, as it has been shown to display functional asymmetries clearly correlated to asymmetric distribution and regulation of biologically relevant molecules. Small non-coding RNAs have been recently implicated in various aspects of neural development. Here, we review cases in which microRNAs are crucial for establishing left–right asymmetries in the C. elegans nervous system. These studies may provide insight into how molecular and functional asymmetries are established in the human brain.
Highlights
MicroRNAs are endogenous 20–24 nt small non-coding RNAs that regulate gene expression through binding to complementary sequences in target messenger RNAs, leading to translational repression and/or cleavage of target mRNAs (Ambros, 2004; He and Hannon, 2004; Bartel, 2009; Chekulaeva and Filipowicz, 2009; Ghildiyal and Zamore, 2009)
While most miRNAs downregulate gene expression, there are examples of miRNA-mediated upregulation of target gene expression during cell cycle arrest, suggesting that miRNA function is complex and context dependent (Vasudevan et al, 2007; Orom et al, 2008). miRNAs have been implicated in many aspects of development and disease including cell cycle, cell differentiation, apoptosis, life span, developmental timing, stress responses, neural development and regeneration, cancers, and neurodegenerative disorders (Boehm and Slack, 2005; Bushati and Cohen, 2007; Chang et al, 2009; Ambros, 2011; Sayed and Abdellatif, 2011; Zhang et al, 2011; Boulias and Horvitz, 2012; Cochella and Hobert, 2012a; Saito and Saito, 2012; Zou et al, 2012, 2013)
In C. elegans, the miRNA lin-4 targets the LIN-14 transcription factor to inhibit netrin-mediated axon attraction (Chang et al, 2004a; Zou et al, 2012), and the miRNA let-7 contributes to a developmental decline in neuronal regeneration (Zou et al, 2013)
Summary
MicroRNAs (miRNAs) are endogenous 20–24 nt small non-coding RNAs that regulate gene expression through binding to complementary sequences in target messenger RNAs (mRNAs), leading to translational repression and/or cleavage of target mRNAs (Ambros, 2004; He and Hannon, 2004; Bartel, 2009; Chekulaeva and Filipowicz, 2009; Ghildiyal and Zamore, 2009). MiRNAs lsy-6, mir-273, and mir-71 function in asymmetric differentiation of two pairs of C. elegans sensory neurons, which will be discussed later (Johnston and Hobert, 2003; Chang et al, 2004b; Hsieh et al, 2012). A study found that 27 genes are differentially expressed in the embryonic human cerebral cortex, and the Lim domain transcription factor LMO4 is more abundant in the right perisylvian cortex than the left, and may be involved in asymmetric development of the cortex (Sun et al, 2005).
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
