Appendix - CNIC

SCIENTIFIC REPORT ´09
> RESEARCH INTEREST
How the genome is co-ordinately regulated during
development is one of the major unanswered questions in
modern biology. We are exploring this issue by means of
comparative and functional approaches, with the aim of
understanding how gene regulatory networks were assembled
during evolution and how this determines their function.
We are particularly interested in understanding the function
of the gene regulatory network that controls embryonic
pluripotency in the mouse embryo. Comparison with other
vertebrates to determine the degree of conservation of these
genes and their interactions shows that the core pluripotency
factors (Oct4-Sox2-Nanog) were newly assembled into a
network in the mammalian lineage and that downstream
1 Cardiovascular Developmental Biology
Functional genomics of embryonic
pluripotency and heart development
Head of Laboratory: Miguel Manzanares
Postdoctoral Researchers: Susana Cañón
Mª. Eva Alonso
Cristina Arias
13
Predoctoral Researchers: Bárbara Pernaute
Beatriz Fernández-Tresguerres
Teresa Rayón
Melisa Gómez-Velázquez
target genes of this core set were recruited through the
appearance of novel enhancer elements. We are also
exploring the role of miRNAs as a second layer of regulation
in the establishment of extraembryonic stem cell
populations.
Another area of interest is the potential regulatory function
during development of intergenic genomic regions that have
been identified with human diseases through genome-wide
studies. These studies include analysis of the genomic
regions associated with increased risk of type II diabetes and
obesity as well as investigation into the role of p63 and its
downstream regulatory network in human disease.
A, The mouse Fgf4 and Sox2 loci are associated with high enhancer activity. ES cells were
transfected with genomic fragments containing the Fgf4 or Sox2 enhancers from mouse (Mm) or
chick (Gg) or with versions in which the minimal mouse functional site was substituted by the
equivalent chick sequence (Mm→Gg) or vice versa (Gg→Mm). B-D, Enhancer activity in transgenic
blastocysts of the mouse Fgf4 3’UTR enhancer (C) and the equivalent chick genomic region (D). The
activity of the mouse Oct4 distal enhancer in the inner cell mass is shown as a positive control (B).