Cellular and Molecular Life Sciences

, Volume 70, Issue 16, pp 2899–2917

Co-ordinating Notch, BMP, and TGF-β signaling during heart valve development

Review

DOI: 10.1007/s00018-012-1197-9

Cite this article as:
Garside, V.C., Chang, A.C., Karsan, A. et al. Cell. Mol. Life Sci. (2013) 70: 2899. doi:10.1007/s00018-012-1197-9

Abstract

Congenital heart defects affect approximately 1–5 % of human newborns each year, and of these cardiac defects 20–30 % are due to heart valve abnormalities. Recent literature indicates that the key factors and pathways that regulate valve development are also implicated in congenital heart defects and valve disease. Currently, there are limited options for treatment of valve disease, and therefore having a better understanding of valve development can contribute critical insight into congenital valve defects and disease. There are three major signaling pathways required for early specification and initiation of endothelial-to-mesenchymal transformation (EMT) in the cardiac cushions: BMP, TGF-β, and Notch signaling. BMPs secreted from the myocardium set up the environment for the overlying endocardium to become activated; Notch signaling initiates EMT; and both BMP and TGF-β signaling synergize with Notch to promote the transition of endothelia to mesenchyme and the mesenchymal cell invasiveness. Together, these three essential signaling pathways help form the cardiac cushions and populate them with mesenchyme and, consequently, set off the cascade of events required to develop mature heart valves. Furthermore, integration and cross-talk between these pathways generate highly stratified and delicate valve leaflets and septa of the heart. Here, we discuss BMP, TGF-β, and Notch signaling pathways during mouse cardiac cushion formation and how they together produce a coordinated EMT response in the developing mouse valves.

Keywords

Heart valve developmentNotchTGF-βBMPCross-talk

Copyright information

© Springer Basel 2012

Authors and Affiliations

  1. 1.Terry Fox LaboratoryBC Cancer AgencyVancouverCanada
  2. 2.Michael Smith Genome Sciences CentreBC Cancer AgencyVancouverCanada
  3. 3.Cell and Developmental Biology ProgramUniversity of British ColumbiaVancouverCanada
  4. 4.Department of Medical GeneticsUniversity of British ColumbiaVancouverCanada
  5. 5.Department of Pathology and Laboratory MedicineUniversity of British ColumbiaVancouverCanada