Chapter 10 The Primary Cilium Coordinates Signaling Pathways in Cell Cycle Control and Migration During Development and Tissue Repair

Christensen, Søren T.; Pedersen, Stine Falsig; Satir, Peter; Veland, Iben R.; Schneider, Linda

doi:10.1016/s0070-2153(08)00810-7

Cited by 140 publications

(126 citation statements)

References 226 publications

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“…Redrawn from Christensen et al, 2008, with hypothesis has been falsified by experiment. In one sense, the second hypothesis is correct -that is, the majority of cells that have primary cilia are non-cycling differentiated cells or stem cells in G 0 .…”

Section: Immunofluorescencementioning

confidence: 99%

“…As indicated in the accompanying poster, the pathways include signaling through Ca 2+ , receptor tyrosine kinases (RTKs), Hedgehog (Hh), Wingless (Wnt), neuronal and purinergic receptors, as well as through communication with the ECM Christensen et al, 2008;Eggenschwiler and Anderson, 2007;Kiprilov et al, 2008;Gerdes et al, 2009;Knight et al, 2009;Masyuk et al, 2008;Praetorius and Leipziger, 2009;Wong and Reiter, 2008;Jensen et al, 2004). A single primary cilium can be set up for several different kinds of signaling and can respond, for example, to mechanical strain as well as to several morphogens, hormones or growth factors.…”

Section: Diversity and Dynamics Of Signaling Pathways In Primary Ciliamentioning

confidence: 99%

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The primary cilium at a glance

Satir

Pedersen

Christensen

2010

Journal of Cell Science

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Section: Immunofluorescencementioning

confidence: 99%

Section: Diversity and Dynamics Of Signaling Pathways In Primary Ciliamentioning

confidence: 99%

The primary cilium at a glance

Satir

Pedersen

Christensen

2010

Journal of Cell Science

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461

405

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“…Primary cilia are microtubule-based organelles, organized in a 9+0 axonemal ultrastructure, which are assembled and maintained via a process termed intraflagellar transport (IFT) in most mammalian cells during growth arrest (Rosenbaum and Witman, 2002;Pedersen et al, 2008). Primary cilia are thought to function as mechano-and chemosensory organelles that specifically coordinate a series of cellular signal transduction pathways during development and in tissue homeostasis, including Hedgehog (Hh), PDGFRα and Wnt signaling (reviewed by Christensen et al, 2008;Wong and Reiter, 2008;Gerdes and Katsanis, 2008). Consequently, defects in assembly of the primary cilium or mutations in ciliary signaling components lead to severe developmental diseases and disorders, now referred to as ciliopathies (reviewed by Pan, 2008;Lehmann et al, 2008;Davenport and Yoder, 2005).…”

Section: E115 Embryos Of the Ift88mentioning

confidence: 99%

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

Clément

Kristensen

Møllgård

et al. 2009

Journal of Cell Science

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100

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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 Ift88tm1Rpw (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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“…Recent data have linked primary cilia to diverse sensory processes, including chemo-and mechanosensation as well as the transduction and/or interpretation of different paracrine signaling cascades (Cardenas-Rodriguez and Badano, 2009;Christensen et al, 2008;Gerdes et al, 2009;Goetz and Anderson, 2010;Wallingford and Mitchell, 2011). Consistent with their broad incidence and diversity of function, ciliary defects can result in a range of clinical manifestations that are shared, to a variable extent, among clinically distinct human genetic disorders, known collectively as ciliopathies (Badano et al, 2006b;Fliegauf et al, 2007).…”

Section: Introductionmentioning

confidence: 99%

Direct role of Bardet–Biedl syndrome proteins in transcriptional regulation

Gascue

Tan

Cárdenas-Rodríguez

et al. 2012

Journal of Cell Science

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SummaryPrimary cilia are conserved organelles that play crucial roles as mechano-and chemosensors, as well as transducing signaling cascades. Consequently, ciliary dysfunction results in a broad range of phenotypes: the ciliopathies. Bardet-Biedl syndrome (BBS), a model ciliopathy, is caused by mutations in 16 known genes. However, the biochemical functions of the BBS proteins are not fully understood. Here we show that the BBS7 protein (localized in the centrosomes, basal bodies and cilia) probably has a nuclear role by virtue of the presence of a biologically confirmed nuclear export signal. Consistent with this observation, we show that BBS7 interacts physically with the polycomb group (PcG) member RNF2 and regulate its protein levels, probably through a proteasome-mediated mechanism. In addition, our data supports a similar role for other BBS proteins. Importantly, the interaction with this PcG member is biologically relevant because loss of BBS proteins leads to the aberrant expression of endogenous RNF2 targets in vivo, including several genes that are crucial for development and for cellular and tissue homeostasis. Our data indicate a hitherto unappreciated, direct role for the BBS proteins in transcriptional regulation and potentially expand the mechanistic spectrum that underpins the development of ciliary phenotypes in patients.

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Chapter 10 The Primary Cilium Coordinates Signaling Pathways in Cell Cycle Control and Migration During Development and Tissue Repair

Cited by 140 publications

References 226 publications

The primary cilium at a glance

The primary cilium at a glance

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

Direct role of Bardet–Biedl syndrome proteins in transcriptional regulation

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