 |
|
|
An Zwijsen
Developmental Signaling
VIB Department of Molecular and Developmental Genetics, K.U.Leuven
PhD: Univ. of Antwerp, Antwerp, Belgium, '95
Postdoc: NIOB, Hubrecht Laboratory, Utrecht, The Netherlands, '95-'97
VIB Group leader since 2008 |
e-mail
phone +32 16 33 00 06
ADDRESS |
Current team members
Group leader: An Zwijsen
Ph.D. Students: Iván Moya, Mariya Dobreva, Paulo Pereira
Support personnel: Elke Maas
Keywords
mouse embryo - stem cell - amnion - cardiovascular development -TGF/Smad
Science
Functional analysis of Bmp-Smad mediated signaling in the mouse embryo
The signaling cascade initiated by bone morphogenetic proteins (BMPs) affects many aspects of life, from fate determination and morphogenesis in embryogenesis to congenital and chronic disease, to tissue repair and homeostasis in adult life. The aim of our research is to study BMP family signaling with a strong emphasis on the BMP-Smads Smad1 and Smad5 and the fine-tuning of the Smad signaling pathway by Smad-interacting proteins in the mouse embryo.
Our research makes use of different unique genetic mouse tools (conventional and conditional Bmp-Smad mouse knockouts and reporter mouse; explant cultures and primary cells derived of these models) to address i) the role of BMP-Smads in amnion plasticity; and ii) the role of BMP-Smads in cardiovascular development. To further unravel the action-mechanism of Bmp-Smads in these processes, we are iii) identifying and characterizing endogenous BMP-Smad interacting proteins.
The amnion is a bilayered, avascular extra-embryonic membrane that envelops and protects the embryo in utero. Although human amniotic membrane transplantations are used in regenerative medicine for about a century to heal skin burns and treat conjunctival defects in ophthalmology, surprisingly little is known about the mechanisms that underlie the plasticity of the amnion. In Smad5 mutants the amnion thickens locally and it undergoes ectopic vasculogenesis, haematopoiesis and in situ development of primordial germ cell (PGC)-like cells/stem cells; as if the mutant amnion develops a teratoma. We explore the basic principles of cell fate determination by Bmp(-Smads) in the murine amnion and lineage switching from a population of apparently uniform amnion cells to amongst others haematopoietic, endothelial and PGC-like cells. The emerging picture seems that Smad5 mediated signalling is pivotal for amnion homeostasis, and that its deficiency in the amnion results in an ectopic signaling center that alters the fate of the amnion.
Cell biological and genetic studies have revealed a direct involvement of TGFβ/BMP signaling in cardiovascular development and disease. Smad5m1\ m1 embryos were shown to develop severe cardiovascular defects. We are addressing the role of BMP-Smad-regulated blood vessel and cardiac development in vivo in the embryo, by conditional deletion of BMP-Smads in different components of the cardiovascular system.
Selected Publications
Umans L, Cox L, Tjwa M, Bito V, Vermeire L, Laperre K, Sipido K, Moons L, Huylebroeck D, Zwijsen A
Inactivation of Smad5 in Endothelial Cells and Smooth Muscle Cells Demonstrates that Smad5 Is Required for Cardiac Homeostasis
AM J PATHOL 170, 1460-72, 2007
Bosman E, Lawson K, Debruyn J, Beek L, Francis A, Schoonjans L, Huylebroeck D, Zwijsen A
Smad5 determines murine amnion fate through the control of bone morphogenetic protein expression and signalling levels
DEVELOPMENT 133, 3399-409, 2006
Search Publications
|
|