Maturation arrest in early postnatal sensory receptors by deletion of the miR-183/96/182 cluster in mouse

被引：49

作者：

Fan, Jianguo ^{[1
]}

Jia, Li ^{[2
]}

Li, Yan ^{[3
]}

Ebrahim, Seham ^{[4
]}

May-Simera, Helen ^{[5
,9
]}

Wood, Alynda ^{[6
]}

Morell, Robert J. ^{[7
]}

Liu, Pinghu ^{[3
]}

Lei, Jingqi ^{[3
]}

Kachar, Bechara ^{[4
]}

Belluscio, Leonardo ^{[6
]}

Qian, Haohua ^{[8
]}

Li, Tiansen ^{[5
]}

Li, Wei ^{[2
]}

Wistow, Graeme ^{[1
]}

Dong, Lijin ^{[3
]}

机构：

[1] NEI, NIH, Mol Struct & Funct Genom Sect, Bethesda, MD 20892 USA

[2] NEI, NIH, Retinal Neurophysiol Sect, Bethesda, MD 20892 USA

[3] NEI, NIH, Genet Engn Core, Bethesda, MD 20892 USA

[4] Natl Inst Deafness & Other Commun Disorders, NIH, Sect Struct Cell Biol, Bethesda, MD 20892 USA

[5] NEI, NIH, Retinal Cell Biol & Degenerat, Bethesda, MD 20892 USA

[6] NINDS, NIH, Dev Neural Plast Sect, Bethesda, MD 20892 USA

[7] Natl Inst Deafness & Other Commun Disorders, NIH, Lab Mol Genet, Bethesda, MD 20892 USA

[8] NEI, NIH, Visual Funct Core, Bethesda, MD 20892 USA

[9] Johannes Gutenberg Univ Mainz, Inst Mol Physiol, Cilia Cell Biol, D-55128 Mainz, Germany

来源：

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 2017年 / 114卷 / 21期

关键词：

miR-183/96/182; cluster; photoreceptors; hair cells; olfactory epithelium; terminal differentiation; PHOTORECEPTOR DEGENERATION; NUCLEAR MIGRATION; RETINA; EZH2; EXPRESSION; PROTEIN; ADULT; LIGHT; DIFFERENTIATION; MORPHOGENESIS;

D O I：

10.1073/pnas.1619442114

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

The polycistronic miR-183/96/182 cluster is preferentially and abundantly expressed in terminally differentiating sensory epithelia. To clarify its roles in the terminal differentiation of sensory receptors in vivo, we deleted the entire gene cluster in mouse germline through homologous recombination. The miR-183/96/ 182 null mice display impairment of the visual, auditory, vestibular, and olfactory systems, attributable to profound defects in sensory receptor terminal differentiation. Maturation of sensory receptor precursors is delayed, and they never attain a fully differentiated state. In the retina, delay in up-regulation of key photoreceptor genes underlies delayed outer segment elongation and possibly mispositioning of cone nuclei in the retina. Incomplete maturation of photoreceptors is followed shortly afterward by early-onset degeneration. Cell biologic and transcriptome analyses implicate dysregulation of ciliogenesis, nuclear translocation, and an epigenetic mechanism that may control timing of terminal differentiation in developing photoreceptors. In both the organ of Corti and the vestibular organ, impaired terminal differentiation manifests as immature stereocilia and kinocilia on the apical surface of hair cells. Our study thus establishes a dedicated role of the miR-183/96/182 cluster in driving the terminal differentiation of multiple sensory receptor cells.

引用

页码：E4271 / E4280

页数：10

共 51 条

[1] Characterization of vestibular dysfunction in the mouse model for Usher syndrome 1F [J].

Alagramam, KN ;

Stahl, JS ;

Jones, SM ;

Pawlowski, KS ;

Wright, CG .

JARO-JOURNAL OF THE ASSOCIATION FOR RESEARCH IN OTOLARYNGOLOGY, 2005, 6 (02) :106-118

[2] Nuclear migration events throughout development [J].

Bone, Courtney R. ;

Starr, Daniel A. .

JOURNAL OF CELL SCIENCE, 2016, 129 (10) :1951-1961

[3] miRNAs 182 and 183 Are Necessary to Maintain Adult Cone Photoreceptor Outer Segments and Visual Function [J].

Busskamp, Volker ;

Krol, Jacek ;

Nelidova, Dasha ;

Daum, Janine ;

Szikra, Tamas ;

Tsuda, Ben ;

Juettner, Josephine ;

Farrow, Karl ;

Scherf, Brigitte Gross ;

Alvarez, Claudia Patricia Patino ;

Genoud, Christel ;

Sothilingam, Vithiyanjali ;

Tanimoto, Naoyuki ;

Stadler, Michael ;

Seeliger, Mathias ;

Stoffel, Markus ;

Filipowicz, Witold ;

Roska, Botond .

NEURON, 2014, 83 (03) :586-600

[4]

CARTERDAWSON LD, 1979, J COMP NEUROL, V188, P245, DOI 10.1002/cne.901880204

[5] Spatiotemporal expression of Ezh2 in the developing mouse cochlear sensory epithelium [J].

Chen, Yan ;

Li, Wenyan ;

Li, Wen ;

Chai, Renjie ;

Li, Huawei .

FRONTIERS OF MEDICINE, 2016, 10 (03) :330-335

[6] Coupling of the nucleus and cytoplasm: role of the LINC complex [J].

Crisp, M ;

Liu, Q ;

Roux, K ;

Rattner, JB ;

Shanahan, C ;

Burke, B ;

Stahl, PD ;

Hodzic, D .

JOURNAL OF CELL BIOLOGY, 2006, 172 (01) :41-53

[7] MicroRNAs couple cell fate and developmental timing in retina [J].

Decembrini, Sarah ;

Bressan, Dario ;

Vignali, Robert ;

Pitto, Letizia ;

Mariotti, Sara ;

Rainaldi, Giuseppe ;

Wang, Xiumei ;

Evangelista, Monica ;

Barsacchi, Giuseppina ;

Cremisi, Federico .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2009, 106 (50) :21179-21184

[8] Night blindness and abnormal cone electroretinogram ON responses in patients with mutations in the GRM6 gene encoding mGluR6 [J].

Dryja, TP ;

McGee, TL ;

Berson, EL ;

Fishman, GA ;

Sandberg, MA ;

Alexander, KR ;

Derlacki, DJ ;

Rajagopalan, AS .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2005, 102 (13) :4884-4889

[9] Specialized Cilia in Mammalian Sensory Systems [J].

Falk, Nathalie ;

Loesl, Marlene ;

Schroeder, Nadja ;

Giessl, Andreas .

CELLS, 2015, 4 (03) :500-519

[10] Genetic insights into the morphogenesis of inner ear hair cells [J].

Frolenkov, GI ;

Belyantseva, IA ;

Friedman, TB ;

Griffith, AJ .

NATURE REVIEWS GENETICS, 2004, 5 (07) :489-498

← 1 2 3 4 5 6 →