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      The cellular and molecular mechanisms of vertebrate lens development

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          Abstract

          The ocular lens is a model system for understanding important aspects of embryonic development, such as cell specification and the spatiotemporally controlled formation of a three-dimensional structure. The lens, which is characterized by transparency, refraction and elasticity, is composed of a bulk mass of fiber cells attached to a sheet of lens epithelium. Although lens induction has been studied for over 100 years, recent findings have revealed a myriad of extracellular signaling pathways and gene regulatory networks, integrated and executed by the transcription factor Pax6, that are required for lens formation in vertebrates. This Review summarizes recent progress in the field, emphasizing the interplay between the diverse regulatory mechanisms employed to form lens progenitor and precursor cells and highlighting novel opportunities to fill gaps in our understanding of lens tissue morphogenesis.

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          ChIP-seq accurately predicts tissue-specific activity of enhancers.

          Axel Visel, Matthew J. Blow, Zirong Li … (2009)
          A major yet unresolved quest in decoding the human genome is the identification of the regulatory sequences that control the spatial and temporal expression of genes. Distant-acting transcriptional enhancers are particularly challenging to uncover because they are scattered among the vast non-coding portion of the genome. Evolutionary sequence constraint can facilitate the discovery of enhancers, but fails to predict when and where they are active in vivo. Here we present the results of chromatin immunoprecipitation with the enhancer-associated protein p300 followed by massively parallel sequencing, and map several thousand in vivo binding sites of p300 in mouse embryonic forebrain, midbrain and limb tissue. We tested 86 of these sequences in a transgenic mouse assay, which in nearly all cases demonstrated reproducible enhancer activity in the tissues that were predicted by p300 binding. Our results indicate that in vivo mapping of p300 binding is a highly accurate means for identifying enhancers and their associated activities, and suggest that such data sets will be useful to study the role of tissue-specific enhancers in human biology and disease on a genome-wide scale.
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            Essential role for Nix in autophagic maturation of erythroid cells.

            Swapan K. Dasgupta, Josef T Prchal, Jin-Wang Wei … (2008)
            Erythroid cells undergo enucleation and the removal of organelles during terminal differentiation. Although autophagy has been suggested to mediate the elimination of organelles for erythroid maturation, the molecular mechanisms underlying this process remain undefined. Here we report a role for a Bcl-2 family member, Nix (also called Bnip3L), in the regulation of erythroid maturation through mitochondrial autophagy. Nix(-/-) mice developed anaemia with reduced mature erythrocytes and compensatory expansion of erythroid precursors. Erythrocytes in the peripheral blood of Nix(-/-) mice exhibited mitochondrial retention and reduced lifespan in vivo. Although the clearance of ribosomes proceeded normally in the absence of Nix, the entry of mitochondria into autophagosomes for clearance was defective. Deficiency in Nix inhibited the loss of mitochondrial membrane potential (DeltaPsi(m)), and treatment with uncoupling chemicals or a BH3 mimetic induced the loss of DeltaPsi(m) and restored the sequestration of mitochondria into autophagosomes in Nix(-/-) erythroid cells. These results suggest that Nix-dependent loss of DeltaPsi(m) is important for targeting the mitochondria into autophagosomes for clearance during erythroid maturation, and interference with this function impairs erythroid maturation and results in anaemia. Our study may also provide insights into molecular mechanisms underlying mitochondrial quality control involving mitochondrial autophagy.
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              FOXO transcription factors: key regulators of cellular quality control.

              Ashley Webb, Anne Brunet (2014)
              FOXO transcription factors are conserved regulators of longevity downstream of insulin signaling. These transcription factors integrate signals emanating from nutrient deprivation and stress stimuli to coordinate programs of genes involved in cellular metabolism and resistance to oxidative stress. Here, we discuss emerging evidence for a pivotal role of FOXO factors in promoting the expression of genes involved in autophagy and the ubiquitin-proteasome system--two cell clearance processes that are essential for maintaining organelle and protein homeostasis (proteostasis). The ability of FOXO to maintain cellular quality control appears to be critical in processes and pathologies where damaged proteins and organelles accumulate, including aging and neurodegenerative diseases. Copyright © 2014 Elsevier Ltd. All rights reserved.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Development
                Journal ID (iso-abbrev): Development
                Journal ID (publisher-id): DEV
                Journal ID (hwp): develop
                Title: Development (Cambridge, England)
                Publisher: The Company of Biologists
                ISSN (Print): 0950-1991
                ISSN (Electronic): 1477-9129
                Publication date (Print): December 2014
                Publication date PMC-release: 1 December 2015
                Volume: 141
                Issue: 23
                Pages: 4432-4447
                Affiliations
                [1 ]Department of Genetics, Albert Einstein College of Medicine , Bronx, NY 10461, USA
                [2 ]Department of Ophthalmology and Visual Sciences, Albert Einstein College of Medicine , Bronx, NY 10461, USA
                [3 ]Sackler School of Medicine and Sagol School of Neuroscience, Tel-Aviv University , 69978 Ramat Aviv, Tel Aviv, Israel
                Author notes
                Article
                Publisher ID: DEV107953
                DOI: 10.1242/dev.107953
                PMC ID: 4302924
                PubMed ID: 25406393
                SO-VID: fe825ac9-f6e1-4dca-978a-2acdbb09b6e5
                Copyright © © 2014. Published by The Company of Biologists Ltd
                License:

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed.

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                Categories
                Subject: Review

                ScienceOpen disciplines: Developmental biology
                Keywords: cell determination,crystallins,differentiation,lens,pax6,pre-placodal region
                Data availability:
                ScienceOpen disciplines: Developmental biology
                Keywords: cell determination, crystallins, differentiation, lens, pax6, pre-placodal region

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