RhoA-mediated apical actin enrichment is required for ciliogenesis and promoted by Foxj1

Pan, Jiehong; You, Yingjian; Huang, Tao; Brody, Steven L.

doi:10.1242/jcs.005306

Cited by 186 publications

(194 citation statements)

References 69 publications

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“…Studies of ciliogenesis in the quail oviduct showed that localization of basal bodies to the apical cell domain depends on actin dynamics 35 . In line with this, ciliogenesis is defective in Foxj1 mutant mice, due to abnormal basal body anchoring to the actin-based apical cytoskeleton, and failure of RhoA-mediated apical actin enrichment [44][45][46][47] . The hypothesis that PCP signaling regulates apical actin network formation required for docking of basal bodies and normal ciliogenesis predicts that mutations in other genes that control PCP in mice should similarly lead to cilia dysfunction and hydrocephalus.…”

mentioning

confidence: 66%

Lack of cadherins Celsr2 and Celsr3 impairs ependymal ciliogenesis, leading to fatal hydrocephalus

et al. 2010

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Cilia are organelles that protrude from the apical surface of most eukaryotic cells. According to their structure and motility, they are classified into three groups 1 . Primary monocilia, present in most cells, lack a central pair of microtubules (9+0 structure), and play several roles in mechanosensation and cell signaling. Nodal cilia have a 9+0 structure but, unlike primary cilia, they move and generate an asymmetric distribution of morphogenetic cues in the node, thereby contributing to laterality 2 . The third group is composed of motile 9+2 cilia that cover epithelial cells lining airways, reproductive tracts, and cerebral ventricles. Motile cilia play crucial functions in clearing mucus and debris in the airways and may assist the transit of sperm and eggs in genital tracts [3][4] . In the early postnatal mammalian brain, neuroepithelial cells that line the cerebral ventricles leave the cell cycle and differentiate into a monolayer of ependymal cells. At the end of maturation, the apical surface of ependymal cells bears dozens of cilia that beat in coordinate manner to facilitate the circulation of the cerebrospinal fluid (CSF), from sites of production in choroid plexuses to sites of absorption in subarachnoid spaces. In mice, mutations in genes involved in the assembly or structure of ependymal cilia, such as Mdnah5 5 , Ift88 (also known as Tg737 or Polaris) 6 , and Hy3 7-8 affect cilia genesis, CSF dynamics, and result in hydrocephalus. Thus far, however, little is known about the genetic factors that govern ependymal cilia polarization and the relationship between the polarity and the development and function of these organelles.Planar cell polarity (PCP), also known as tissue polarity, controls the polarization of epithelial cells in a plane perpendicular to their apicobasal axis. It was initially described in Drosophila, where it affects the stereotypic arrangement of cuticular hairs, sensory bristles, and Supplementary Fig. 1a, b). RT-PCR and (Supplementary Fig. 1c).Using the knocked-in beta-galactosidase reporter, we monitored the expression of Celsr2 in heterozygous mice. Consistent with published data [24][25][26] , Celsr2 expression was detected in all brain areas, from E11.5 to P5 (Fig. 1a-h). Celsr2 mutant mice develop progressive hydrocephalusCelsr2 mutant mice were viable and fertile, except for some females that had vaginal atresia. At birth, their brain did not display any flagrant morphological abnormality, suggesting that Celsr2 is not critical for cerebral embryonic development. However, a progressive ventricular dilation appeared between P5 and P10 with variable severity between animals, and became evident at P21 (Fig. 2a,b).The lateral ventricles were enlarged, and the septum had an abnormal triangular shape, due to 6 6 reduction of the dorsal part of the lateral septum. We did not observe any stenosis or constriction at the level of the foramen of Monro or of the aqueduct. The subcommissural organ (SCO), a structure thought to play a role in non-communicating hydrocephalus, was...

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confidence: 66%

Lack of cadherins Celsr2 and Celsr3 impairs ependymal ciliogenesis, leading to fatal hydrocephalus

et al. 2010

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“…5b, arrows). In addition, the microvilli, which interspaced the axonema, appeared to be reduced in length as well as in number, compared with the WT samples from the same litter, reminiscent of actin organization or Rho GTPase activity defect 32,33 . Thus, in mutant cells basal bodies multiply normally but fail to migrate apically, suggesting a defect in transport and/or docking at the apical membrane.…”

Section: Cyld Interacts With Cap350 At the Centrosome/basal Bodiesmentioning

confidence: 97%

The deubiquitinating enzyme CYLD controls apical docking of basal bodies in ciliated epithelial cells

et al. 2014

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CYLD is a tumour suppressor gene mutated in familial cylindromatosis, a genetic disorder leading to the development of skin appendage tumours. It encodes a deubiquitinating enzyme that removes Lys63-or linear-linked ubiquitin chains. CYLD was shown to regulate cell proliferation, cell survival and inflammatory responses, through various signalling pathways. Here we show that CYLD localizes at centrosomes and basal bodies via interaction with the centrosomal protein CAP350 and demonstrate that CYLD must be both at the centrosome and catalytically active to promote ciliogenesis independently of NF-kB. In transgenic mice engineered to mimic the smallest truncation found in cylindromatosis patients, CYLD interaction with CAP350 is lost disrupting CYLD centrosome localization, which results in cilia formation defects due to impairment of basal body migration and docking. These results point to an undiscovered regulation of ciliogenesis by Lys63 ubiquitination and provide new perspectives regarding CYLD function that should be considered in the context of cylindromatosis.

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“…The forkhead transcription factor Foxj1 is required for ciliogenesis and also involved in the organization of the apical membrane. 39 In the differentiated pseudostratified epithelium, Foxj1 is present and expressed at the same level in most cell nuclei of the epithelium. In ␣BTX-exposed cultures, Foxj1 is still present in the basal progenitor cells of the epithelium, but its expression is much lower in the intermediate cells and finally absent in the upper part of the epithelium ( Figure 7D).…”

Section: The ␣7 Nachr Is Involved In the Differentiation Pathway Of Tmentioning

confidence: 99%

α7 Nicotinic Acetylcholine Receptor Regulates Airway Epithelium Differentiation by Controlling Basal Cell Proliferation

Maouche

Polette

Jolly

et al. 2009

The American Journal of Pathology

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Airway epithelial basal cells are known to be critical for regenerating injured epithelium and maintaining tissue homeostasis. Recent evidence suggests that the ␣7 nicotinic acetylcholine receptor (nAChR), which is highly permeable to Ca 2؉ , is involved in lung morphogenesis. Here, we have investigated the potential role of the ␣7 nAChR in the regulation of airway epithelial basal cell proliferation and the differentiation of the human airway epithelium. In vivo during fetal development and in vitro during the regeneration of the human airway epithelium, ␣7 nAChR expression coincides with epithelium differentiation. Inactivating ␣7 nAChR function in vitro increases cell proliferation during the initial steps of the epithelium regeneration, leading to epithelial alterations such as basal cell hyperplasia and squamous metaplasia, remodeling observed in many bronchopulmonary diseases. The regeneration of the airway epithelium after injury in ␣7 The respiratory epithelium, which is constantly exposed to airborne pollutants, is frequently injured, which results in altered epithelial functions. To restore these functions, the respiratory epithelium must undergo rapid repair via epithelial cell spreading and migration and regenerate its structure via basal cell proliferation and differentiation.

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RhoA-mediated apical actin enrichment is required for ciliogenesis and promoted by Foxj1

Cited by 186 publications

References 69 publications

Lack of cadherins Celsr2 and Celsr3 impairs ependymal ciliogenesis, leading to fatal hydrocephalus

Lack of cadherins Celsr2 and Celsr3 impairs ependymal ciliogenesis, leading to fatal hydrocephalus

The deubiquitinating enzyme CYLD controls apical docking of basal bodies in ciliated epithelial cells

α7 Nicotinic Acetylcholine Receptor Regulates Airway Epithelium Differentiation by Controlling Basal Cell Proliferation

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