Title

Notch signaling plays a key role in cardiac cell differentiation

UMMS Affiliation

Department of Medicine and Cell Biology; Department of Physiology

Date

7-18-2006

Document Type

Article

Subjects

Animals; Biological Markers; *Cell Differentiation; Chick Embryo; Gene Expression Regulation, Developmental; Heart; Myocardium; RNA, Messenger; Receptor, Notch1; *Signal Transduction

Disciplines

Life Sciences | Medicine and Health Sciences

Abstract

Results from lineage tracing studies indicate that precursor cells in the ventricles give rise to both cardiac muscle and conduction cells. Cardiac conduction cells are specialized cells responsible for orchestrating the rhythmic contractions of the heart. Here, we show that Notch signaling plays an important role in the differentiation of cardiac muscle and conduction cell lineages in the ventricles. Notch1 expression coincides with a conduction marker, HNK-1, at early stages. Misexpression of constitutively active Notch1 (NIC) in early heart tubes in chick exhibited multiple effects on cardiac cell differentiation. Cells expressing NIC had a significant decrease in expression of cardiac muscle markers, but an increase in expression of conduction cell markers, HNK-1, and SNAP-25. However, the expression of the conduction marker connexin 40 was inhibited. Loss-of-function study, using a dominant-negative form of Suppressor-of-Hairless, further supports that Notch1 signaling is important for the differentiation of these cardiac cell types. Functional studies show that the expression of constitutively active Notch1 resulted in abnormalities in ventricular conduction pathway patterns.

Rights and Permissions

Citation: Mech Dev. 2006 Aug;123(8):626-40. Epub 2006 Jul 14. Link to article on publisher's site

DOI of Published Version

10.1016/j.mod.2006.06.003

Related Resources

Link to Article in PubMed

Journal Title

Mechanisms of development

PubMed ID

16843648