LINE elements as mediators of genomic variability and neuronal plasticity in the brain: development of a zebrafish model

• Applicant: Dr. Thomas Widmann
• Subject Area: Developmental Neurobiology
• Term: from 2011 to 2013
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 212150453

The human genome is largely composed of non-coding DNA, only 3-5% codes for exons. The majority of the non-coding DNA is however fundamental for the correct functioning and regulation of the genome. Transposable elements (TEs) like LINEs generated up to 50% of the human genome during evolution. They can mobilize, causing mutations but also conferring genomic plasticity. The generation of new insertions in the germ line led to the concept of TEs as ‘selfish’ DNA. However, inconsistent with their hereditary transmission, it was recently shown by the host lab and others that most of the action of TEs occurs in somatic cells, especially in the human brain.Thus, to deeply understand the impact of the somatic activity of LINE elements, we propose to develop and use zebrafish (Danio rerio) as a model organism for LINE transposition. It contains several active LINE elements, of which Zfl2-2 is the most similar one to human LINEs. With this model, we aim to answer the following: 1) Are LINEs active in the Central Nervous System (CNS) of other organisms? 2) Are LINEs active in other somatic tissues? 3) What’s the impact of LINE activity in the CNS of zebrafish? 4) Does LINE activity in the CNS of zebrafish have any phenotypic consequence?To answer these questions, we will map the site of new LINE insertions during development, using a LINE reporter cassette and deep sequencing, on samples from ecto-, meso-, and endoderm germ layers, and from the developing brain. We aim to detect hot spots of LINE integration, allowing the analysis of possible genetic and phenotypic consequences. In-vivo imaging of LINE transposition during zebrafish development will further show us tissues where transposition occurs with higher frequency, and possible phenotypic alterations. We therefore hope to detect new principles of genomic plasticity that could regulate gene expression. Especially in the brain this could regulate neuronal plasticity and ultimately cognition and behaviour

• DFG Programme: Research Fellowships
• International Connection: Spain
• Host: Dr. José Luis Garcia-Pérez