Developmental biology: The early heart remodelled

Abstract

What factors direct the formation of heart muscle in the developing embryo? Unexpectedly, a chromatin-remodelling protein complex turns out to be a crucial determinant of cardiac-cell fate.

Figure 1. A chromatin-remodelling complex instructs heart development

Takeuchi and Bruneau induced the expression of the cardiac-specific Baf60c subunit and the transcription factor Gata4 in mouse embryonic tissues outside the heart developmental fields. a, Transfected Baf60c probably assembles with the other ten BAF subunits to form a cardiogenic BAF complex (cBAF). Baf60a and Baf60b are not incorporated into cBAF. b, cBAF seems to bind to target loci, perhaps by multivalent recognition through histone- and DNA-binding domains. c, cBAF recruits Gata4 through a presumed interaction between Baf60c and Gata4, which results in the expression of heart-specific genes. The arrangement of subunits in the BAF complex is not yet established.

Figure 2. The genetic circuitry regulating heart development

In mammals, extracellular signals act directly or indirectly to produce localized expression of the BAF complex subunit Baf60c and the transcription factor Gata4 in the area of the embryo that gives rise to the heart. Baf60c and Gata4 work together with another cardiogenic transcription factor, Tbx5, to activate genes encoding other regulators of heart development — Mef2, Nkx2–5, Hand and Isl1. These directly activate certain muscle-specific genes. Additional steps, requiring Tbx5, organize synchronous activity of cardiac muscle cells, giving rise to beating heart muscle. (Modified from ref. .)