The emerging face of primary cilia

Department of Medicine, Division of Endocrinology, Diabetes, and Nutrition, University of Maryland School of Medicine, Baltimore, Maryland, USA.
genesis (Impact Factor: 2.04). 04/2011; 49(4):231-46. DOI: 10.1002/dvg.20728
Source: PubMed

ABSTRACT Primary cilia are microtubule-based organelles that serve as hubs for the transduction of various developmental signaling pathways including Hedgehog, Wnt, FGF, and PDGF. Ciliary dysfunction contributes to a range of disorders, collectively known as the ciliopathies. Recently, interest has grown in these syndromes, particularly among craniofacial biologists, as many known and putative ciliopathies have severe craniofacial defects. Herein we discuss the current understanding of ciliary biology and craniofacial development in an attempt to gain insight into the molecular etiology for craniofacial ciliopathies, and uncover a characteristic ciliopathic craniofacial gestalt.

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    ABSTRACT: While kidney injury is associated with re-expression of numerous Wnt ligands and receptors, molecular mechanisms which underlie regulation of distinct Wnt signaling pathways and ensuing biological consequences remain incompletely understood. Primary cilia are increasingly being recognized as cellular 'antennae' which sense and transduce signals from the microenvironment, particularly through Wnt signaling. Here, we explored the role of cilia as modulators of canonical and non-canonical Wnt signaling activities involving tubular epithelial cells in the injured kidney. We demonstrate that in the mouse model of unilateral ureter obstruction, progression of kidney injury correlates with increased expression of numerous Wnt ligands, and that increased expression of Wnt ligands corresponded with over-activation of canonical Wnt signaling. In contrast, non-canonical Wnt signaling dropped significantly during the course of kidney injury despite gradually increased expression of typical non-canonical and intermediate Wnt signaling ligands. We further demonstrate that in cultured tubular epithelial cells, cilia modulate balance between canonical and non-canonical signaling responses upon exposure to Wnt ligands. We provide evidence that in the context of renal injury, primary cilia act as molecular switches between canonical and non-canonical Wnt signaling activity, possibly determining between regenerative and pro-fibrotic effects of Wnt re-expression in the injured kidney.
    Fibrogenesis & Tissue Repair 12/2015; 8(1). DOI:10.1186/s13069-015-0024-y
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    ABSTRACT: Primary cilia are cell surface, microtubule-based organelles that dynamically extend from cells to receive and process molecular and mechanical signaling cues. In the last decade, this organelle has gained increasing popularity due to its ability to act as a cellular antenna, receive molecular stimuli, and respond to the cell's environment. A growing field of data suggests that various tissues utilize and interpret the loss of cilia in different ways. Thus, careful examination of the role of cilia on individual cell types and tissues is necessary. Neural crest cells (NCCs) are an excellent example of cells that survey their environment for developmental cues. In this review, we discuss how NCCs utilize primary cilia during their ontogenic development, paying special attention to the role primary cilia play in processing developmental signals required for NCC specification, migration, proliferation, and differentiation. We also discuss how the loss of functional cilia on cranial and trunk NCCs affects the development of various organ systems to which they contribute. A deeper understanding of ciliary function could contribute greatly to understanding the molecular mechanisms guiding NCC development and differentiation. Furthermore, superimposing the ciliary contribution on our current understanding of NCC development identifies new avenues for therapeutic intervention in neurocristopathies. © 2015 Elsevier Inc. All rights reserved.
    Current Topics in Developmental Biology 01/2015; 111:97-134. DOI:10.1016/bs.ctdb.2014.11.004 · 4.21 Impact Factor
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    ABSTRACT: Context: Ciliopathies are a group of rare conditions that present through a wide range of manifestations. Given the relative common occurrence of defects of the GH/IGF-1 axis in children with short stature and growth retardation, the association between ciliopathies and these defects needs further attention. Case: Our patient is a boy who was born at term and noted to have early growth retardation and weight gain within the first 18 months of life. Biochemical tests demonstrated low IGF-1 but a normal peak GH on stimulation and an adequate rise in IGF-1 on administration of rhGH. An MRI scan revealed pituitary hypoplasia and an ectopic posterior pituitary. His growth responded well to rhGH therapy. Subsequently he also developed a retinopathy of his rods and cones, metaphyseal dysplasia and hypertension with renal failure requiring renal replacement therapy. Whole exome sequencing demonstrated compound heterozygous mutations of IFT172, thus consistent with a ciliopathy. Conclusions: This is the first reported case of a child with a mutation in IFT172 who presented with growth retardation in early childhood and was initially managed as a case of functional GH deficiency that responded to rhGH therapy. This case highlights the importance of ciliary function in pituitary development and the link between early onset growth failure and ciliopathies.
    Journal of Clinical Endocrinology &amp Metabolism 02/2015; 100(4):jc20143852. DOI:10.1210/jc.2014-3852 · 6.31 Impact Factor


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