Comparative analysis of Delta-like 1 regulatory elements during brain development using transgenic mice

LÓPEZ-LEAL RODRIGO; RUBINSTEIN MARCELO; FRANCHINI LUCÍA F.

Congreso; Society for Neuroscience 2011; 2011

The gene Delta-like 1 (Dll1) has been implicated in the proliferation/differentiation switch of neural precursors during brain development. Dll1 encodes a ligand of Notch that inhibits the differentiation of neuronal precursors, allowing them to proliferate and to increase the undifferentiated progenitor pool. The expression of Dll1 is thighly controlled during brain development but the regions and mechanisms controlling its expression are not completely known. Previous works have shown that a region located 4.3 kb upstream of Dll1 (4.3-Dll1) drives the expression of the reporter gene lacZ in a subdomain of the endogenous expression pattern. In additon, in our laboratory we have identified an additional region located at 5.9 kb of Dll1 (5.9-Dll1) that controls the expression of a reporter gene in an overlapping manner to the endogenous gene pattern. In this work we have performed a comparison of these two regulatory regions in order to identify the unique properties of each region. Using transgenic mice expressing fluorescent proteins under the control of 4.3-Dll1 and/or 5.9-Dll1 and with the aid of cell markers we have performed a detailed temporo-spatial study of coexpression and colocalization during mouse development. Our results show that the region 4.3-Dll1 showed an extended spatio-temporal expression pattern related to the endogenous Dll1 pattern indicating that some inhibitory regions are missing. On the other hand, 5.9-Dll1 drove reporter expression in a more restricted spatio-temporal manner suggesting that this region is a more specific enhancer that controls Dll1 expression at particular time points and places during brain development. Our data brings new information into the understanding of the regulation of Dll1 expression during brain development.   Acknowledgements: DID-UACH D-2010-7 and CONICYT to RRL; ANPCyT and CONICET to LFF; HHMI to MR.