Cell autonomous roles for AP‐2α in lens vesicle separation and maintenance of the lens epithelial cell phenotype

Pontoriero, Giuseppe; Deschamps, Paula; Ashery‐Padan, Ruth; Wong, Ryan; Yang, Ying; Zavadil, Jiří; Cvekl, Aleš; Sullivan, S; Williams, Trevor; West‐Mays, Judith A.

doi:10.1002/dvdy.21445

Cited by 58 publications

(69 citation statements)

References 78 publications

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“…An important part of these morphogenetic movements is the separation of the lens vesicle from the surface ectoderm that subsequently gives rise to the corneal epithelium. This process is disrupted in AP-2α −/− [147], Cited2 −/− [148], Foxe3 −/− [149], Pax6 +/− [150], Rxra −/− ;Rarg −/− [151], Rbpj −/− [152], and Sox11 −/− [153]. A cooperative action of E- and N-cadherins and spatialy regulated apoptosis are required to initiate and complete these cell separations [154].…”

Section: Lens Morphogenesis and Gene Regulatory Networkmentioning

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: Lens Morphogenesis and Gene Regulatory Networkmentioning

confidence: 99%

Signaling and Gene Regulatory Networks in Mammalian Lens Development

2017

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“…This might be due to unidentified function(s) mediated by Shroom3 that are distinct from those involving p120-catenin. Several mouse mutants that display a similar lens stalk phenotype have disruptions in additional morphogenetic processes, such as proliferation, adhesion, differentiation and apoptosis, leaving open the possibility that Shroom3 might also function in these processes (Dimanlig et al, 2001;Ozeki et al, 2001;Medina-Martinez et al, 2005;Yoshimoto et al, 2005;Chen et al, 2008;Pontoriero et al, 2008Pontoriero et al, , 2009Kuracha et al, 2011;Cavalheiro et al, 2014).…”

Section: P120-catenin and Shroom3 Are Required For Normal Lens Morphomentioning

confidence: 99%

p120-catenin-dependent junctional recruitment of Shroom3 is required for apical constriction during lens pit morphogenesis

et al. 2014

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Apical constriction (AC) is a widely utilized mechanism of cell shape change whereby epithelial cells transform from a cylindrical to conical shape, which can facilitate morphogenetic movements during embryonic development. Invertebrate epithelial cells undergoing AC depend on the contraction of apical cortex-spanning actomyosin filaments that generate force on the apical junctions and pull them toward the middle of the cell, effectively reducing the apical circumference. A current challenge is to determine whether these mechanisms are conserved in vertebrates and to identify the molecules responsible for linking apical junctions with the AC machinery. Utilizing the developing mouse eye as a model, we have uncovered evidence that lens placode AC may be partially dependent on apically positioned myosin-containing filaments associated with the zonula adherens. In addition we found that, among several junctional components, p120-catenin genetically interacts with Shroom3, a protein required for AC during embryonic morphogenesis. Further analysis revealed that, similar to Shroom3, p120-catenin is required for AC of lens cells. Finally, we determined that p120-catenin functions by recruiting Shroom3 to adherens junctions. Together, these data identify a novel role for p120-catenin during AC and further define the mechanisms required for vertebrate AC.

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“…Immunolabeling for Ap-2a, a factor involved in lens vesicle separation (Pontoriero et al, 2008), revealed expression in the epithelial cells and in the lens vesicle cells at E10.5 for both wild-type and ak lens (Fig. 2B).…”

Section: Pitx3 Directly Regulates Foxe3 743mentioning

confidence: 99%

Pitx3 directly regulates Foxe3 during early lens development

Ahmad¹,

Aslam²,

Muenster³

et al. 2013

Int. J. Dev. Biol.

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Pitx3 is a bicoid-related homeodomain transcription factor critical for the development of the ocular lens, mesencephalic dopaminergic neurons and skeletal muscle. In humans, mutations in PITX3 are responsible for cataracts and anterior segment abnormalities of varying degree; polymorphisms are associated with Parkinson's disease. In aphakia (ak) mice, two deletions in the promoter region of Pitx3 cause abnormal lens development. Here, we investigated systematically the role of Pitx3 in lens development including its molecular targets responsible for the ak phenotype. We have shown that ak lenses exhibit reduced proliferation and aberrant fiber cell differentiation. This was associated with loss of Foxe3 expression, complete absence of Prox1 expression, reduced expression of e-tubulin and earlier expression of g-crystallin during lens development. Using EMSA and ChIP assays, we demonstrated that Pitx3 binds to an evolutionary conserved bicoid-binding site on the 5'-upstream region of Foxe3. Finally, Pitx3 binding to 5'-upstream region of Foxe3 increased transcriptional activity significantly in a cell-based reporter assay. Identification of Foxe3 as a transcriptional target of Pitx3 explains at least in part some of the phenotypic similarities of the ak and dyl mice (dysgenic lens, a Foxe3 allele). These findings enhance our understanding of the molecular cascades which subserve lens development.

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Cell autonomous roles for AP‐2α in lens vesicle separation and maintenance of the lens epithelial cell phenotype

Cited by 58 publications

References 78 publications

Signaling and Gene Regulatory Networks in Mammalian Lens Development

Signaling and Gene Regulatory Networks in Mammalian Lens Development

p120-catenin-dependent junctional recruitment of Shroom3 is required for apical constriction during lens pit morphogenesis

Pitx3 directly regulates Foxe3 during early lens development

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