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

Christian A Clement; Stine G Kristensen; Kjeld Møllgård; Gregory J Pazour; Bradley K Yoder; Lars A Larsen; Søren Tvorup Christensen

doi:10.1242/jcs.049676

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

Christian A Clement, Stine G Kristensen, Kjeld Møllgård, Gregory J Pazour, Bradley K Yoder, Lars A Larsen, Søren Tvorup Christensen

75 Citations (Scopus)

Abstract

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.

Original language	English
Journal	Journal of Cell Science
Volume	122
Issue number	Pt 17
Pages (from-to)	3070-82
Number of pages	12
ISSN	0021-9533
DOIs	https://doi.org/10.1242/jcs.049676
Publication status	Published - 2009

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title = "The primary cilium coordinates early cardiogenesis and hedgehog signaling in cardiomyocyte differentiation",

abstract = "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.",

author = "Clement, {Christian A} and Kristensen, {Stine G} and Kjeld M{\o}llg{\aa}rd and Pazour, {Gregory J} and Yoder, {Bradley K} and Larsen, {Lars A} and Christensen, {S{\o}ren Tvorup}",

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doi = "10.1242/jcs.049676",

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pages = "3070--82",

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T1 - The primary cilium coordinates early cardiogenesis and hedgehog signaling in cardiomyocyte differentiation

AU - Clement, Christian A

AU - Kristensen, Stine G

AU - Møllgård, Kjeld

AU - Pazour, Gregory J

AU - Yoder, Bradley K

AU - Larsen, Lars A

AU - Christensen, Søren Tvorup

PY - 2009

Y1 - 2009

N2 - 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.

AB - 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.

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DO - 10.1242/jcs.049676

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SP - 3070

EP - 3082

JO - Journal of Cell Science

JF - Journal of Cell Science

IS - Pt 17

ER -

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

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