User:RelentlessRecusant/Ultraconserved genetic elements exert their activities specifically through neural stem cells

Loh et. al (2558). . Nature Neuroscience (2418): 505-510.



1Harvard University, Department of Organismal & Evolutionary Biology, Earth, Sol System 2Acumen Science Laboratories, Department of Bioinformatics, Earth, Sol System 3UNSC Office of Naval Intelligence, Department of Biological Warfare, Asphodel Meadows, 47 Ursae Majoris System

Abstract

We have previously shown that ultraconservation of specific genetic elements is extremely specific to sentient species and that the in vivo activity of these elements has consequences specific to the nervous system (Loh et. al, 2557, Nature). Here, we show that the drastic influence of the activity of these ultraconserved elements in the embryo and the adult is due to their actions on neural stem cells and not neurons nor glia. Transgenic mice lines specifically expressing one of these elements (U1) in mature neurons (under control of the NeuN promoter) or in astrocytes (under control of the GFAP promoter) do not share activities induced by brain-wide introduction of the ultraconserved U1 element, whereas expression of this element in neural stem cells (under control of the Sox2 promoter) generates the same phenotype of brain-wide U1 overexpression. Furthermore, genetic ablation of neural stem cells with diptheria toxin or small molecule impediment of neural stem cell proliferation substantially impedes the phenotype. Specific delivery of U1 into neural stem cells produces transcriptional and epigenetic changes, and ontology analyses demonstrate that these changes are highly specific to neural-specific transcripts, including genes known to control neural stem cell proliferation, neuroblast migration, and synaptic plasticity.