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First published online 4 August 2009
doi: 10.1242/jcs.049676

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The primary cilium coordinates early cardiogenesis and hedgehog signaling in cardiomyocyte differentiation

¹ Department of Biology, University of Copenhagen, Universitetsparken 13, DK-2100 Copenhagen, Denmark
² Department of Cellular and Molecular Medicine, University of Copenhagen, Blegdamsvej 3, DK-2200 Copenhagen, Denmark
⁵ Wilhelm Johannsen Centre for Functional Genome Research, University of Copenhagen, Blegdamsvej 3, DK-2200 Copenhagen, Denmark
³ University of Massachusetts Medical School Worcester, Worcester, MA 01655, USA
⁴ The University of Alabama at Birmingham, Birmingham, AL 35294, USA

^* Author for correspondence (stchristensen{at}bio.ku.dk)

Accepted 29 May 2009

Defects in the assembly or function of primary cilia, which are sensory organelles, are tightly coupled to developmental defects and diseases in mammals. Here, we investigated the function of the primary cilium in regulating hedgehog signaling and early cardiogenesis. We report that the pluripotent P19.CL6 mouse stem cell line, which can differentiate into beating cardiomyocytes, forms primary cilia that contain essential components of the hedgehog pathway, including Smoothened, Patched-1 and Gli2. Knockdown of the primary cilium by Ift88 and Ift20 siRNA or treatment with cyclopamine, an inhibitor of Smoothened, blocks hedgehog signaling in P19.CL6 cells, as well as differentiation of the cells into beating cardiomyocytes. E11.5 embryos of the Ift88^tm1Rpw (Ift88-null) mice, which form no cilia, have ventricular dilation, decreased myocardial trabeculation and abnormal outflow tract development. These data support the conclusion that cardiac primary cilia are crucial in early heart development, where they partly coordinate hedgehog signaling.

Key words: Primary cilia, P19.CL6 cells, Cardiac development, Mouse, Heart, Hedgehog signaling, siRNA, Ift88, Ift20, Cyclopamine

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				C. A. Clement, S. G. Kristensen, K. Mollgard, G. J. Pazour, B. K. Yoder, L. A. Larsen, and S. T. Christensen The primary cilium coordinates early cardiogenesis and hedgehog signaling in cardiomyocyte differentiation Development, September 15, 2009; 136(18): e1 - e1. [Full Text]