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The activity of Mouse cerberus like 2 during cardiogenesis: genetic and morphogenetic studies
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Abstract(s)
The heart is the first organ that becomes functional in the vertebrate embryo. Heart
morphogenesis is a complex process, with precise control developmental mechanisms,
that can nevertheless fail. There are morphological aspects as polarity of the heart
intrinsically related with the three body axes, anterior?posterior (A-P), dorsal?ventral
(D-V), and left?right (L-R). The L-R axis has became subject of many studies in recent
years and was found that the heart undergoes multiple morphogenetic processes, which
are governed by this axis. Development of internal organs proceeds across the L-R axis
and gain shape during organogenesis as a result of the early asymmetric activation of
the conserved Nodal signalling cascade, in the left lateral plate mesoderm (Hamada et
al., 2002). A Cerberus/Dan family member, mouse cerberus-like2 (cerl-2) is
asymmetrically expressed on the right side of the mouse node and encodes for a
secreted protein that binds directly to nodal restricting the Nodal signalling pathway
towards the left side by preventing its activity in the right side (Marques et al, 2004).
Preliminary studies showed that cerl-2 knockout (KO) mice display multiple laterality
defects including heart?s rotation failure and randomization of organs? position due to
L/R axis disruption. In addition, was observed several cardiac defects as severe
hyperplasia of the myocardium and incomplete atria formation and ventricular septation
that may not be explained by laterality abnormalities. In this study, were conducted
morphological analyses of cerl-2 KO newborns, histological sections of newborn hearts
and WISH with Gata-4, mefc2, hand and fgf8 probes on embryos throughout heart
development (7,5dpc to 10.5dpc). Furthermore, a new compound mouse line cerl-
2KO::mlc1vlacZ was generated which will help to identify the contribution of the
Secondary Heart Field (SHF) to the cerl-2KO heart defects. This body of work leads to
the suggestion that, in addition to the previously described laterality-related defects,
another distinct mechanism may contribute to the spectrum of complex cardiac defects
in cerl-2 KO mice that cannot be explained only by the disruption of the nodal cascade
in LPM.
Problems in heart morphogenesis lead to congenital heart disease, which is the most
common form of birth defect in humans (Harvey, 2002; Olson and Schenider, 2003).
Abstract
Description
Dissertação mest., Ciências Biomédicas, Universidade do Algarve, 2009
Keywords
Teses Genética Cardiologia Morfogenética Ratos Doenças congénitas