Differential regulation of node formation, nodal ciliogenesis and cilia positioning by <i>Noto</i> and <i>Foxj1</i>

Alten, Leonie; Schuster-Gossler, Karin; Beckers, Anja; Groos, Stephanie; Ulmer, Bärbel; Hegermann, Jan; Ochs, Matthias; Gossler, Achim

doi:10.1242/dev.072728

Cited by 46 publications

(24 citation statements)

References 55 publications

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“…The RFX transcription factors act at early stages in the ciliogenesis program, and their dysfunction affects both motile and sensory primary cilia [19, 20]. Moreover, RFX2 and RFX3 share program with FOXJ1, and are potential candidates for mutations that causes PCD [21-24]. …”

Section: Programs Of Ciliogenesismentioning

confidence: 99%

Genetics and biology of primary ciliary dyskinesia

Horani

Ferkol

Dutcher

et al. 2016

Paediatric Respiratory Reviews

156

168

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Summary Ciliopathies are a growing class of disorders caused by abnormal ciliary axonemal structure and function. Our understanding of the complex genetic and functional phenotypes of these conditions has rapidly progressed. Primary ciliary dyskinesia (PCD) remains the sole genetic disorder of motile cilia dysfunction. However, unlike many Mendelian genetic disorders, PCD is not caused by mutations in a single gene or locus, but rather, autosomal recessive mutation in one of many genes that lead to a similar phenotype. The first reported PCD mutations, more than a decade ago, identified genes encoding known structural components of the ciliary axoneme. In recent years, mutations in genes encoding novel cytoplasmic and regulatory proteins have been discovered. These findings have provided new insights into the functions of the motile cilia, and a better understanding of motile cilia disease. Advances in genetic tools will soon allow more precise genetic testing, mandating that clinicians must understand the genetic basis of PCD. Here, we review genetic mutations, their biological impact on cilia structure and function, and the implication of emerging genetic diagnostic tools.

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Section: Programs Of Ciliogenesismentioning

confidence: 99%

Genetics and biology of primary ciliary dyskinesia

Horani

Ferkol

Dutcher

et al. 2016

Paediatric Respiratory Reviews

156

168

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“…Overexpression of FoxJ1 is sufficient to confer some motile functions on primary cilia in both D. renio and X. tropicalis [49], [50]. Functional diversification of specific subsets of motile cilia involves other transcription factors including the homeobox NOTO for nodal cilia [53], [54], as well as MYB and nuclear MULTICILIN for multiciliated epithelia [55], [56].…”

Section: Introductionmentioning

confidence: 99%

HEATR2 Plays a Conserved Role in Assembly of the Ciliary Motile Apparatus

et al. 2014

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Cilia are highly conserved microtubule-based structures that perform a variety of sensory and motility functions during development and adult homeostasis. In humans, defects specifically affecting motile cilia lead to chronic airway infections, infertility and laterality defects in the genetically heterogeneous disorder Primary Ciliary Dyskinesia (PCD). Using the comparatively simple Drosophila system, in which mechanosensory neurons possess modified motile cilia, we employed a recently elucidated cilia transcriptional RFX-FOX code to identify novel PCD candidate genes. Here, we report characterization of CG31320/HEATR2, which plays a conserved critical role in forming the axonemal dynein arms required for ciliary motility in both flies and humans. Inner and outer arm dyneins are absent from axonemes of CG31320 mutant flies and from PCD individuals with a novel splice-acceptor HEATR2 mutation. Functional conservation of closely arranged RFX-FOX binding sites upstream of HEATR2 orthologues may drive higher cytoplasmic expression of HEATR2 during early motile ciliogenesis. Immunoprecipitation reveals HEATR2 interacts with DNAI2, but not HSP70 or HSP90, distinguishing it from the client/chaperone functions described for other cytoplasmic proteins required for dynein arm assembly such as DNAAF1-4. These data implicate CG31320/HEATR2 in a growing intracellular pre-assembly and transport network that is necessary to deliver functional dynein machinery to the ciliary compartment for integration into the motile axoneme.

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“…During LR axis development the canonical Wnt/β-catenin pathway initiates the expression of the transcription factor Foxj1 , a master regulator of motile cilia, in the SM [16]–[18]. The SM represents a part of the epithelial outer layer of the gastrula embryo.…”

Section: Introductionmentioning

confidence: 99%

Wnt11b Is Involved in Cilia-Mediated Symmetry Breakage during Xenopus Left-Right Development

et al. 2013

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Breakage of bilateral symmetry in amphibian embryos depends on the development of a ciliated epithelium at the gastrocoel roof during early neurulation. Motile cilia at the gastrocoel roof plate (GRP) give rise to leftward flow of extracellular fluids. Flow is required for asymmetric gene expression and organ morphogenesis. Wnt signaling has previously been involved in two steps, Wnt/ß-catenin mediated induction of Foxj1, a regulator of motile cilia, and Wnt/planar cell polarity (PCP) dependent cilia polarization to the posterior pole of cells. We have studied Wnt11b in the context of laterality determination, as this ligand was reported to activate canonical and non-canonical Wnt signaling. Wnt11b was found to be expressed in the so-called superficial mesoderm (SM), from which the GRP derives. Surprisingly, Foxj1 was only marginally affected in loss-of-function experiments, indicating that another ligand acts in this early step of laterality specification. Wnt11b was required, however, for polarization of GRP cilia and GRP morphogenesis, in line with the known function of Wnt/PCP in cilia-driven leftward flow. In addition Xnr1 and Coco expression in the lateral-most GRP cells, which sense flow and generate the first asymmetric signal, was attenuated in morphants, involving Wnt signaling in yet another process related to symmetry breakage in Xenopus.

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Differential regulation of node formation, nodal ciliogenesis and cilia positioning by Noto and Foxj1

Cited by 46 publications

References 55 publications

Genetics and biology of primary ciliary dyskinesia

Genetics and biology of primary ciliary dyskinesia

HEATR2 Plays a Conserved Role in Assembly of the Ciliary Motile Apparatus

Wnt11b Is Involved in Cilia-Mediated Symmetry Breakage during Xenopus Left-Right Development

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