Group leader: An Zwijsen

PhD: Univ. of Antwerp, Antwerp, Belgium, '95
Postdoc: NIOB, Hubrecht Laboratory, Utrecht, The Netherlands, '95-'97
VIB Group leader since 2008

Research interests

Growth and differentiation of an embryo is dependent on the integrated function of various polypeptide growth factors. The principal growth factor signalling pathway studied within the group is that of Transforming Growth Factor type b  (Tgfb) / bone morphogenetic proteins (Bmps). Members of the R-Smad family are substrates for type I receptor kinase activity in liganded typeI/type II receptor complexes. Activation of Smad1, -5 and/or -8 (by BMPs, GDFs) or of Smad2 and/or -3 (by nodals, activins, TGFβs) induces complex formation with Smad4. This Smad complex translocates to the nucleus were it participates in gene transcription regulation, via interactions with other co-factors. The lab of Danny Huylebroeck identified Smad1 and -5 quite some time ago and analyzed their BMP-like effects in Xenopus embryos injected with RNA encoding full-length (or deletion mutants of) Smad5. Thereafter, we decided to study the function(s) of Smad5 in the establishment of the mammalian body plan during embryogenesis. Both conventional and conditional Smad5 deficient mice and cells provide a solid basis for our molecular and developmental driven research.
Smad5 deficient embryos have revealed several new functions for Smad5 that were not anticipated from classic in vitro studies. Currently our in vivo studies focus on the function of Smad5 in amnion homeostasis, in endothelium and cardiac morphogenesis. In adiition, we study Smad5-interacting proteins.
In order to understand Smad5 function in particular, and BMP-Smad function in general, in the vertebrate embryo and to explain the defects in our mutant Smad5 models we identify and characterize endogenous Smad5 interacting proteins (S5IPs).
We also exploit embryonic stem (ES) cells in chimaeric embryos composed of mutant and wild-type cells and in in vitro differentiation assays to help us to refine our understanding of Smad5 gene function and its target genes and their regulation.

Key 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. 2007 May;170(5):1460-72. PMID: 17456754
• Bosman EA, Lawson KA, 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. 2006 Sep;133(17):3399-409
• Umans L, Vermeire L, Francis A, Chang H, Huylebroeck D, Zwijsen A. (2003) Generation of a floxed allele of Smad5 for cre-mediated conditional knockout in the mouse. Genesis. 37, 5-11.
  Chang H, Zwijsen A, Vogel H, Huylebroeck D, Matzuk MM. (2000) Smad5 is essential for left-right asymmetry in mice. Dev Biol. 219, 71-8.
• Chang H, Huylebroeck D, Verschueren K, Guo Q, Matzuk MM, Zwijsen A. (1999) Smad5 knockout mice die at mid-gestation due to multiple embryonic and extraembryonic defects. Development 126, 1631-42.
• Goumans MJ, Zwijsen A, van Rooijen MA, Huylebroeck D, Roelen BA, Mummery CL. (1999) Transforming growth factor-beta signalling in extraembryonic mesoderm is required for yolk sac vasculogenesis in mice. Development. 126, 3473-83.

Research team