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(Circulation Research. 2009;105:408.)
© 2009 American Heart Association, Inc.

Review

Heart Valve Development

Regulatory Networks in Development and Disease

Michelle D. Combs, Katherine E. Yutzey

From the Division of Molecular Cardiovascular Biology, Cincinnati Children’s Hospital Medical Center, Ohio.

Correspondence to Katherine E. Yutzey, Division of Molecular Cardiovascular Biology, Cincinnati Children’s Hospital Medical Center ML7020, 240 Albert Sabin Way, Cincinnati, OH 45229. E-mail Katherine.Yutzey{at}cchmc.org

This Review is part of a thematic series on Developmental Biology, which includes the following articles:

Signaling Pathways Controlling Second Heart Field Development [2009;104:933–942]

Heart Valve Development: Regulatory Networks in Development and Disease

The Forgotten Lineage: Cardiac Fibroblasts and the Role of Periostin

Conduction System Specification

Coronary Artery Development–Myocardial Vessel Interaction

Myocyte Development–Specification/Epicardium
Elizabeth McNally Editor

Abstract: In recent years, significant advances have been made in the definition of regulatory pathways that control normal and abnormal cardiac valve development. Here, we review the cellular and molecular mechanisms underlying the early development of valve progenitors and establishment of normal valve structure and function. Regulatory hierarchies consisting of a variety of signaling pathways, transcription factors, and downstream structural genes are conserved during vertebrate valvulogenesis. Complex intersecting regulatory pathways are required for endocardial cushion formation, valve progenitor cell proliferation, valve cell lineage development, and establishment of extracellular matrix compartments in the stratified valve leaflets. There is increasing evidence that the regulatory mechanisms governing normal valve development also contribute to human valve pathology. In addition, congenital valve malformations are predominant among diseased valves replaced late in life. The understanding of valve developmental mechanisms has important implications in the diagnosis and management of congenital and adult valve disease.

Key Words: valvulogenesis • developmental biology • cell signaling • extracellular matrix • transcriptional regulation