HB-EGF function in cardiac valve development requires interaction with heparan sulfate proteoglycans

• DOI: 10.1242/dev.048926
• Publication Date: 2010-06-08T11:47:51Z
• Authors: Ryo Iwamoto; Naoki Mine; Taichiro Kawaguchi; Seigo Minami; Kazuko Saeki; Eisuke Mekada
• Keywords: Mesenchyme; Heart development

HB-EGF, a member of the EGF family growth factors, plays an important role in cardiac valve development by suppressing mesenchymal cell proliferation. Here, we show that HB-EGF must interact with heparan sulfate proteoglycans (HSPGs) to properly function this process. In developing valves, is synthesized endocardial cells but accumulates mesenchyme interacting HSPGs. Disrupting interaction between and HSPGs ex vivo model cushion explants resulted increased Moreover, homozygous knock-in mice (HB(Delta)(hb/)(Delta)(hb)) expressing mutant cannot bind developed enlarged valves hyperproliferation cells; phenotype resembled Hbegf-null mice. Interestingly, although had abnormal heart chambers lung alveoli, HB(Delta)(hb/)(Delta)(hb) did not exhibit these defects. These results indicate interactions are essential for especially development, which suppresses