@article {2051,
	title = {Cilia-associated wound repair mediated by IFT88 in retinal pigment epithelium.},
	journal = {Sci Rep},
	volume = {13},
	year = {2023},
	month = {2023 May 21},
	pages = {8205},
	abstract = {<p>Primary cilia are conserved organelles that integrate extracellular cues into intracellular signals and are critical for diverse processes, including cellular development and repair responses. Deficits in ciliary function cause multisystemic human diseases known as ciliopathies. In the eye, atrophy of the retinal pigment epithelium (RPE) is a common feature of many ciliopathies. However, the roles of RPE cilia in vivo remain poorly understood. In this study, we first found that mouse RPE cells only transiently form primary cilia. We then examined the RPE in the mouse model of Bardet-Biedl Syndrome 4 (BBS4), a ciliopathy associated with retinal degeneration in humans, and found that ciliation in BBS4 mutant RPE cells is disrupted early during development. Next, using a laser-induced injury model in vivo, we found that primary cilia in RPE reassemble in response to laser injury during RPE wound healing and then rapidly disassemble after the repair is completed. Finally, we demonstrated that RPE-specific depletion of primary cilia in a conditional mouse model of cilia loss promoted wound healing and enhanced cell proliferation. In summary, our data suggest that RPE cilia contribute to both retinal development and repair and provide insights into potential therapeutic targets for more common RPE degenerative diseases.</p>
},
	keywords = {Animals, Cilia, Ciliopathies, Disease Models, Animal, Humans, Mice, Microtubule-Associated Proteins, Retinal Degeneration, Retinal Pigment Epithelium, Tumor Suppressor Proteins},
	issn = {2045-2322},
	doi = {10.1038/s41598-023-35099-3},
	author = {Ning, Ke and Bhuckory, Mohajeet B and Lo, Chien-Hui and Sendayen, Brent E and Kowal, Tia J and Chen, Ming and Bansal, Ruchi and Chang, Kun-Che and Vollrath, Douglas and Berbari, Nicolas F and Mahajan, Vinit B and Hu, Yang and Sun, Yang}
}
@article {117,
	title = {Disruption of mouse Cenpj, a regulator of centriole biogenesis, phenocopies Seckel syndrome.},
	journal = {PLoS Genet},
	volume = {8},
	year = {2012},
	month = {2012},
	pages = {e1003022},
	abstract = {<p>Disruption of the centromere protein J gene, CENPJ (CPAP, MCPH6, SCKL4), which is a highly conserved and ubiquitiously expressed centrosomal protein, has been associated with primary microcephaly and the microcephalic primordial dwarfism disorder Seckel syndrome. The mechanism by which disruption of CENPJ causes the proportionate, primordial growth failure that is characteristic of Seckel syndrome is unknown. By generating a hypomorphic allele of Cenpj, we have developed a mouse (Cenpj(tm/tm)) that recapitulates many of the clinical features of Seckel syndrome, including intrauterine dwarfism, microcephaly with memory impairment, ossification defects, and ocular and skeletal abnormalities, thus providing clear confirmation that specific mutations of CENPJ can cause Seckel syndrome. Immunohistochemistry revealed increased levels of DNA damage and apoptosis throughout Cenpj(tm/tm) embryos and adult mice showed an elevated frequency of micronucleus induction, suggesting that Cenpj-deficiency results in genomic instability. Notably, however, genomic instability was not the result of defective ATR-dependent DNA damage signaling, as is the case for the majority of genes associated with Seckel syndrome. Instead, Cenpj(tm/tm) embryonic fibroblasts exhibited irregular centriole and centrosome numbers and mono- and multipolar spindles, and many were near-tetraploid with numerical and structural chromosomal abnormalities when compared to passage-matched wild-type cells. Increased cell death due to mitotic failure during embryonic development is likely to contribute to the proportionate dwarfism that is associated with CENPJ-Seckel syndrome.</p>
},
	keywords = {Animals, Apoptosis, Centrioles, DNA Damage, Dwarfism, Embryonic Development, Genomic Instability, Mice, Mice, Transgenic, Microcephaly, Microtubule-Associated Proteins, Mitosis, Mitotic Spindle Apparatus, Mutation, Signal Transduction},
	author = {McIntyre, Rebecca E and Lakshminarasimhan Chavali, Pavithra and Ismail, Ozama and Carragher, Damian M and Sanchez-Andrade, Gabriela and Forment, Josep V and Fu, Beiyuan and Del Castillo Velasco-Herrera, Martin and Edwards, Andrew and van der Weyden, Louise and Yang, Fengtang and Ramirez-Solis, Ramiro and Estabel, Jeanne and Gallagher, Ferdia A and Logan, Darren W and Arends, Mark J and Tsang, Stephen H and Mahajan, Vinit B and Scudamore, Cheryl L and White, Jacqueline K and Jackson, Stephen P and Gergely, Fanni and Adams, David J}
}
