Cilia and coordination of signaling networks during heart development

Koefoed, Klaus; Veland, Iben R.; Pedersen, Lotte B.; Larsen, Lars Allan; Christensen, Søren T.

doi:10.4161/org.27483

Cited by 81 publications

(76 citation statements)

References 228 publications

(325 reference statements)

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“…The loss of primary cilia at cardiac cushions is crucial for the Tgfβ/Alk5 (Tgfβr1)-dependent endMT of chick endocardial cells, which is induced by shear stress (Egorova et al, 2011a,b;Ten Dijke et al, 2012). Hence, it is possible that the bending and stability of cilia, which are differentially distributed within the cardiac tube in a flow-dependent manner, could generate sensory inputs that might explain why endocardial cells exhibit different responses to flow within different regions of the cardiac tube (Koefoed et al, 2014).…”

Section: Mechanosensitive Pathways Within the Endocardiummentioning

confidence: 99%

The force within: endocardial development, mechanotransduction and signalling during cardiac morphogenesis

Haack

Abdelilah‐Seyfried

2016

Development

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Endocardial cells are cardiac endothelial cells that line the interior of the heart tube. Historically, their contribution to cardiac development has mainly been considered from a morphological perspective. However, recent studies have begun to define novel instructive roles of the endocardium, as a sensor and signal transducer of biophysical forces induced by blood flow, and as an angiocrine signalling centre that is involved in myocardial cellular morphogenesis, regeneration and reprogramming. In this Review, we discuss how the endocardium develops, how endocardial-myocardial interactions influence the developing embryonic heart, and how the dysregulation of blood flowresponsive endocardial signalling can result in pathophysiological changes.

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Section: Mechanosensitive Pathways Within the Endocardiummentioning

confidence: 99%

The force within: endocardial development, mechanotransduction and signalling during cardiac morphogenesis

Haack

Abdelilah‐Seyfried

2016

Development

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“…The exact mechanisms underlying CHD in OFD syndromes or other ciliopathies are currently unknown. Both nodal and primary cardiac cilia belong to the group of primary cilia and play a crucial role in early heart development (Koefoed, Veland, Pedersen, Larsen, & Christensen, 2014). Nodal cilia are a key player in the establishment of the embryonic left‐right axis as they coordinate numerous embryonic signaling pathways (including the Hedgehog pathway) which are involved in cardiogenesis.…”

Section: Discussionmentioning

confidence: 99%

“…A significant clinical overlap between heterotaxy‐syndromes and ciliopathies was further illustrated in a later report (Karp, Grosse‐Wortmann, & Bowdin, 2012). In addition, it can be hypothesized that left‐sided obstruction defects are not the direct result of laterality defects as these are established during cardiac morphogenesis and maturation in the post‐gastrulational phase (Koefoed et al, 2014). …”

Section: Discussionmentioning

confidence: 99%

Oral‐facial‐digital syndrome type 1 in males: Congenital heart defects are included in its phenotypic spectrum

Bouman

Alders

Oostra

et al. 2017

American J of Med Genetics Pt A

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Oral‐facial‐digital syndrome type 1 (OFD1; OMIM# 311200) is an X‐linked dominant ciliopathy caused by mutations in the OFD1 gene. This condition is characterized by facial anomalies and abnormalities of oral tissues, digits, brain, and kidneys. Almost all affected patients are female, as OFD1 is presumed to be lethal in males, mostly in the first or second trimester of pregnancy. Live born males with OFD1 are a rare occurrence, with only five reported patients to date. In four patients the presence of a congenital heart defect (CHD) was observed. Here, we report an affected male fetus with a hemizygous de novo mutation in OFD1 (c.2101C>T; p.(Gln701*)). Ultrasound examination demonstrated severe hydrocephalus, a hypoplastic cerebellum and a hypoplastic left ventricle of the heart. The pregnancy was terminated at 16 weeks of gestation because of poor prognosis. Post‐mortem examination of the fetus confirmed severe hypoplasia of the left ventricle of the heart. We emphasize that CHDs should be included in the phenotypic spectrum of OFD1 in males. This justifies molecular analysis of OFD1 when CHD is encountered prenatally in combination with one or more phenotypic features previously described in the OFD1 gene alteration spectrum. The underlying pathogenesis of CHD in OFD1 (and other ciliopathies) probably involves dysfunction of the primary cilia regarding coordination of left‐right signalling during early heart development. Whether these CHDs wholly or partly result from defective left right signalling, in which different types of cilia are known to play a critical role, remains a topic of research.

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“…These left-right asymmetry defects can have a particularly important impact on heart development, as discussed in the accompanying article by Christensen and colleagues. 20 However, as these authors point out, some congenital heart defects may arise during later development as a result of defective signaling from primary cilia in cardiac tissues. Indeed, what is now becoming clear is the diversity and pleiotropy of organ involvement that is seen in ciliopathies whose major pathological consequences seem to arise from loss of function of primary cilia.…”

Section: Ciliary Signaling Organ Development and Human Diseasementioning

confidence: 99%