An unanticipated discourse of HB-EGF with VANGL2 signaling during embryo implantation. Academic Article uri icon

abstract

  • Implantation is the first direct encounter between the embryo and uterus during pregnancy, and Hbegf is the earliest known molecular signaling for embryo-uterine crosstalk during implantation. The downstream effectors of heparin-binding EGF (HB-EGF) in implantation remain elusive due to the complexity of EGF receptor family. This study shows that the formation of implantation chamber (crypt) triggered by HB-EGF is disrupted by uterine deletion of Vangl2, a key planar cell polarity component (PCP). We found that HB-EGF binds to ERBB2 and ERBB3 to recruit VANGL2 for tyrosine phosphorylation. Using in vivo models, we show that uterine VAGL2 tyrosine phosphorylation is suppressed in Erbb2/Erbb3 double conditional knockout mice. In this context, severe implantation defects in these mice lend support to the critical role of HB-EGF-ERBB2/3-VANGL2 in establishing a two-way dialogue between the blastocyst and uterus. In addition, the result addresses an outstanding question how VANGL2 is activated during implantation. Taken together, these observations reveal that HB-EGF regulates the implantation process by influencing uterine epithelial cell polarity comprising VANGL2.

published proceedings

  • Proc Natl Acad Sci U S A

altmetric score

  • 5.08

author list (cited authors)

  • Kim, Y. S., Yuan, J., Dewar, A., Borg, J., Threadgill, D. W., Sun, X., & Dey, S. K.

citation count

  • 0

complete list of authors

  • Kim, Yeon Sun||Yuan, Jia||Dewar, Amanda||Borg, Jean-Paul||Threadgill, David W||Sun, Xiaofei||Dey, Sudhansu K

publication date

  • May 2023