Lineage Tracing of Neuronal Progenitor Cells Expressing dlx1a/2a in the Zebrafish Brain

Title: Lineage Tracing of Neuronal Progenitor Cells Expressing dlx1a/2a in the Zebrafish Brain
Authors: Feng, Shengrui
Date: 2014
Abstract: The Distal-less homeobox (Dlx) genes encode homeodomain transcription factors that play important roles in the development of limbs, sensory organs, branchial arches and the forebrain. In the forebrain, Dlx1 and Dlx2 are expressed in neuronal progenitor cells and play essential roles in GABAergic neuron differentiation and migration. In order to understand the fate of neuronal progenitor cells that express dlx1a/2a genes in the brain, we produced lines of Tg(dlx1a/2a:CreERT2) transgenic fish expressing the CreERT2 recombinase driven by regulatory elements from the dlx1a/2a locus. CreERT2 expression in these fish faithfully recapitulates that of dlx1a/2a genes in the forebrain. These fish were mated with Tg(ubi:Switch) reporter fish that express a loxP-flanked GFP gene followed by mCherry, driven by the ubiquitin promoter. Upon tamoxifen treatment, the double transgenic fish express mCherry in dlx1a/2a-expressing cells. Live imaging data showed that mCherry-expressing cells were observed first in the telencephalon and prethalamus, regions from which they migrated and populated the telencephalon, prethalamus and hypothalamus by 10dpf. Fate mapping of mCherry-expressing cells in double transgenic fish demonstrated that a majority of dlx1a/2a-expressing cells give rise to GABAergic neurons. Furthermore, as zebrafish produce new neurons throughout life, the role of dlx1a/2a during adult neurogenesis was examined. Our preliminary data showed that dlx1a/2a-expressing progenitor cells populate various domains of the forebrain during adult neurogenesis. Our lineage tracing system provides a powerful tool to investigate the origin of GABAergic neuron progenitors and the mechanisms by which they populate or repopulate the adult brain.
CollectionThèses, 2011 - // Theses, 2011 -