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editorial
. 2016 Jan 13;9:509. doi: 10.3389/fnins.2015.00509

Figure 1.

Figure 1

CAG expansion in the human HTT gene leads to Huntington's Disease (HD): possible contribution of altered non-coding RNA transcription and aberrant developmental processes are described. (A) Top pie charts report the proportion of coding and noncoding RNAs in the human genome (Alexander et al., 2010). Highlighted in the coding portion of the genome, the Huntington's Disease gene (HTT). Wild type or expanded CAG lengths are indicated by sepia and gray colors, respectively. Bottom pie charts summarize the relative contribution of single classes of non-coding RNAs (Baker, 2011) to normal (sepia) or diseased (gray) organism physiology. The contribution of non-coding RNA transcription to HD process is still not fully dissected. (B) Schematic representation of human development at different stages [blastocyst (5 days) and 25 days embryos, 100 days and 5 months fetuses and adult organism] is shown. Normal (sepia) and mutant huntingtin [expanded HTT gene] (grayscale) expression is found in the whole organism at any given developmental stage (MacDonald et al., 2003; Gusella and MacDonald, 2006). Molecular mechanisms (miRNAs, lncRNAs, alterative splicing, histone modifications and chromatin remodeling) acting since conception in the organism bearing the mutation are represented by the gray area. (C) A simplified representation of HD brain development is shown. Developmental stages as in (B). Different color's shades denote specific brain regions such as telencephalon, diencephalon, midbrain, and hindbrain which develop differently to originate adult brain structures. Light gray lines across the head designate coronal sections unveiling inner brain organization, while puzzle pieces represent various cell types constituting each brain district. It is evident that the presence of mutant huntingtin (expanded HTT gene) places any cell of the organism—and of the brain in particular—in a “different biological state” with subtle cellular and tissue development alterations that culminate in the overt symptoms appearing in adult life. The changes induced by the expression of CAG-repeat HTT expansion compromise MSN-generating stem cells specification and prime MSN to adult neuronal degeneration (Molero et al., 2009; Humbert, 2010).