Autophagy in the lens

Morishita, Hideaki; Mizushima, Noboru

doi:10.1016/j.exer.2015.08.019

Cited by 58 publications

(41 citation statements)

References 76 publications

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“…Requirements for their intracellular transport, quality control, and assembly provide numerous excellent opportunities to study fundamentals of cytoplasmic membrane biogenesis, organelle degradation and turnover [252–254], recycling of materials via autophagy [252, 255], developmental endoplasmatic reticulum stress and unfolded protein response [256], function of the ubiquitin proteasome systems [228, 257, 258], protein sorting into raft and nonraft bilayers [259, 260], remodeling of membrane cytoskeleton [261, 262], and formation of mechanical stiffness and elasticity of the lens [263–265] (Box 1, 2) and to expand studies of GRNs and extracellular signaling to include genes that either control (e.g. Gata3, Hsf4, Prox1, Sox1, and etc) or function in these processes (e.g.…”

Section: Discussionmentioning

confidence: 99%

Signaling and Gene Regulatory Networks in Mammalian Lens Development

2017

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Ocular lens development represents an advantageous system to study regulatory mechanisms governing cell fate decisions, extracellular signaling, cell and tissue organization, and underlying gene regulatory networks. Spatiotemporaly regulated domains of BMP, FGF, and other signaling molecules in the late gastrula-early neurula stage embryos generate the border region between the neural plate and non-neural ectoderm from which multiple cell types, including lens progenitor cells, emerge and undergo initial tissue formation. Extracellular signaling and DNA-binding transcription factors govern lens and optic cup morphogenesis. Pax6, c-Maf, Hsf4, Prox1, Sox1, and a few additional factors regulate expression of the lens structural proteins, the crystallins. A multitude of cross-talks between a diverse array of signaling pathways control the complexity and order of the lens morphogenetic processes and its transparency.

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Section: Discussionmentioning

confidence: 99%

Signaling and Gene Regulatory Networks in Mammalian Lens Development

2017

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“…In addition, lamin B phosphorylation mediated by Cdk1, a process that occurs during normal mitosis, is required for denucleation (Caceres et al, 2010;Chaffee et al, 2014). Further experiments are required to probe signaling upstream of JNK/mTOR, the phosphorylation of lamin B by Cdk1, and yet to be identified steps in the cascade of cellular and molecular events leading to nuclear degradation in lens fibers (Morishita and Mizushima, 2016). For example, a recent study has revealed a novel role of p27 Kip1 , upstream of Cdk1, in lens fiber cell denucleation (Lyu et al, 2016).…”

Section: Kip2mentioning

confidence: 99%

Chromatin remodeling enzyme Snf2h regulates embryonic lens differentiation and denucleation

Limi

McGreal

et al. 2016

Development

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Ocular lens morphogenesis is a model for investigating mechanisms of cellular differentiation, spatial and temporal gene expression control, and chromatin regulation. Brg1 (Smarca4) and Snf2h (Smarca5) are catalytic subunits of distinct ATP-dependent chromatin remodeling complexes implicated in transcriptional regulation. Previous studies have shown that Brg1 regulates both lens fiber cell differentiation and organized degradation of their nuclei (denucleation). Here, we employed a conditional Snf2h flox mouse model to probe the cellular and molecular mechanisms of lens formation. Depletion of Snf2h induces premature and expanded differentiation of lens precursor cells forming the lens vesicle, implicating Snf2h as a key regulator of lens vesicle polarity through spatial control of Prox1, Jag1, p27Kip1 (Cdkn1b) and p57Kip2 (Cdkn1c) gene expression. The abnormal Snf2h −/− fiber cells also retain their nuclei. RNA profiling of Snf2h −/− and Brg1 −/− eyes revealed differences in multiple transcripts, including prominent downregulation of those encoding Hsf4 and DNase IIβ, which are implicated in the denucleation process. In summary, our data suggest that Snf2h is essential for the establishment of lens vesicle polarity, partitioning of prospective lens epithelial and fiber cell compartments, lens fiber cell differentiation, and lens fiber cell nuclear degradation.

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“…Autophagic vacuoles engulfing mitochondria were reported in the lens in 1984 [43,44]. Autophagy was the expected pathway of choice for the developing lens' fiber cells to degrade cell organelles to create the organelle-free zone (reviewed in [45]). Autophagosomes were reported in both differentiating primary and secondary lens fiber cells [43,46].…”

Section: Autophagy In the Healthy And Aging Eyementioning

confidence: 99%

Autophagy in Ocular Pathophysiology

Mitter¹,

Boulton²

2016

Autophagy in Current Trends in Cellular Physiology and Pathology

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Autophagy is an evolutionarily conserved intracellular recycling pathway that is indispensable for cellular quality control. Dysfunctional autophagy has been associated with several neurodegenerative, myodegenerative, infectious, and cancerous disorders. Autophagic processes are not only important for cellular maintenance in the retina but also intimately involved with phagocytosis and the very core of retinal visual process. Additionally, excessively upregulated autophagy may culminate into a cell death modality, which may be detrimental to the non-dividing cells of various eye segments. Major advances have been made in understanding the role and fate of autophagy in different ocular tissue layers. In this chapter, we summarize the current understanding of autophagy in the eye in the context of development, aging, and disease. We also speculate on the putative therapeutic strategies where autophagy may be incorporated to treat oculopathies.

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Autophagy in the lens

Cited by 58 publications

References 76 publications

Signaling and Gene Regulatory Networks in Mammalian Lens Development

Signaling and Gene Regulatory Networks in Mammalian Lens Development

Chromatin remodeling enzyme Snf2h regulates embryonic lens differentiation and denucleation

Autophagy in Ocular Pathophysiology

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