Techniques for investigating lncRNA transcript functions in neurodevelopment

Long noncoding RNAs (lncRNAs) are sequences of 200 nucleotides or more that are transcribed from a large portion of the mammalian genome. While hypothesized to have a variety of biological roles, many lncRNAs remain largely functionally uncharacterized due to unique challenges associated with their investigation. For example, some lncRNAs overlap with other genomic loci, are expressed in a cell-type-specific manner, and/or are differentially processed at the post-transcriptional level. The mammalian CNS contains a vast diversity of lncRNAs, and lncRNAs are highly abundant in the mammalian brain. However, interrogating lncRNA function in models of the CNS, particularly in vivo, can be complex and challenging. Here we review the breadth of methods used to investigate lncRNAs in the CNS, their merits, and the understanding they can provide with respect to neurodevelopment and pathophysiology. We discuss remaining challenges in the field and provide recommendations to assay lncRNAs based on current methods.