Talk:Vision - Lens Development

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Cite this page: Hill, M.A. (2024, February 27) Embryology Vision - Lens Development. Retrieved from


Eye morphogenesis driven by epithelial flow into the optic cup facilitated by modulation of bone morphogenetic protein

Elife. 2015 Feb 24;4. doi: 10.7554/eLife.05216.

Heermann S1, Schütz L1, Lemke S1, Krieglstein K2, Wittbrodt J1.


The hemispheric, bi-layered optic cup forms from an oval optic vesicle during early vertebrate eye development through major morphological transformations. The overall basal surface, facing the developing lens, is increasing, while, at the same time, the space basally occupied by individual cells is decreasing. This cannot be explained by the classical view of eye development. Using zebrafish (Danio rerio) as a model, we show that the lens-averted epithelium functions as a reservoir that contributes to the growing neuroretina through epithelial flow around the distal rims of the optic cup. We propose that this flow couples morphogenesis and retinal determination. Our 4D data indicate that future stem cells flow from their origin in the lens-averted domain of the optic vesicle to their destination in the ciliary marginal zone. BMP-mediated inhibition of the flow results in ectopic neuroretina in the RPE domain. Ultimately the ventral fissure fails to close resulting in coloboma. KEYWORDS: BMP antagonist; coloboma; developmental biology; neuroretinal flow; neuroscience; optic cup; optic fissure; optic vesicle; stem cells; zebrafish

PMID 25719386

© 2015, Heermann et al This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited.

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The cellular and molecular mechanisms of vertebrate lens development

Development. 2014 Dec;141(23):4432-47. doi: 10.1242/dev.107953. Epub 2014 Nov 18.

Cvekl A1, Ashery-Padan R2.


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. © 2014. Published by The Company of Biologists Ltd. KEYWORDS: Cell determination; Crystallins; Differentiation; Lens; Pax6; Pre-placodal region

PMID 25406393

Pax6-dependent, but β-catenin-independent, function of Bcl9 proteins in mouse lens development

Genes Dev. 2014 Sep 1;28(17):1879-84. doi: 10.1101/gad.246140.114.

Cantù C1, Zimmerli D1, Hausmann G1, Valenta T1, Moor A2, Aguet M2, Basler K3.


Bcl9 and Bcl9l (Bcl9/9l) encode Wnt signaling components that mediate the interaction between β-catenin and Pygopus (Pygo) via two evolutionarily conserved domains, HD1 and HD2, respectively. We generated mouse strains lacking these domains to probe the β-catenin-dependent and β-catenin-independent roles of Bcl9/9l and Pygo during mouse development. While lens development is critically dependent on the presence of the HD1 domain, it is not affected by the lack of the HD2 domain, indicating that Bcl9/9l act in this context in a β-catenin-independent manner. Furthermore, we uncover a new regulatory circuit in which Pax6, the master regulator of eye development, directly activates Bcl9/9l transcription. © 2014 Cantù et al.; Published by Cold Spring Harbor Laboratory Press. KEYWORDS: Bcl9; Pax6; Pygopus; Wnt; lens induction; mouse

PMID 25184676

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

Development. 2014 Aug;141(16):3177-87. doi: 10.1242/dev.107433. Epub 2014 Jul 18.

Lang RA1, Herman K2, Reynolds AB3, Hildebrand JD4, Plageman TF Jr5.


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. © 2014. Published by The Company of Biologists Ltd. KEYWORDS: Apical constriction; Invagination; Lens pit morphogenesis; Shroom3; delta1 catenin (Ctnnd1); p120-catenin

PMID 25038041


Neural crest cells organize the eye via TGF-β and canonical Wnt signalling

Nat Commun. 2011 Apr;2:265.

Grocott T, Johnson S, Bailey AP, Streit A. Source Department of Craniofacial Development, King's College London, Guy's Campus, London SE1 9RT, UK.


In vertebrates, the lens and retina arise from different embryonic tissues raising the question of how they are aligned to form a functional eye. Neural crest cells are crucial for this process: in their absence, ectopic lenses develop far from the retina. Here we show, using the chick as a model system, that neural crest-derived transforming growth factor-βs activate both Smad3 and canonical Wnt signalling in the adjacent ectoderm to position the lens next to the retina. They do so by controlling Pax6 activity: although Smad3 may inhibit Pax6 protein function, its sustained downregulation requires transcriptional repression by Wnt-initiated β-catenin. We propose that the same neural crest-dependent signalling mechanism is used repeatedly to integrate different components of the eye and suggest a general role for the neural crest in coordinating central and peripheral parts of the sensory nervous system.

PMID: 21468017


Genetic and epigenetic mechanisms of gene regulation during lens development

Cvekl A, Duncan MK. Prog Retin Eye Res. 2007 Nov;26(6):555-97. Epub 2007 Jul 28. Review.

Recent studies demonstrated a number of links between chromatin structure, gene expression, extracellular signaling and cellular differentiation during lens development. Lens progenitor cells originate from a pool of common progenitor cells, the pre-placodal region (PPR) which is formed from a combination of extracellular signaling between the neural plate, naïve ectoderm and mesendoderm. A specific commitment to the lens program over alternate choices such as the formation of olfactory epithelium or the anterior pituitary is manifested by the formation of a thickened surface ectoderm, the lens placode. Mouse lens progenitor cells are characterized by the expression of a complement of lens lineage-specific transcription factors including Pax6, Six3 and Sox2, controlled by FGF and BMP signaling, followed later by c-Maf, Mab21like1, Prox1 and FoxE3. Proliferation of lens progenitors together with their morphogenetic movements results in the formation of the lens vesicle. This transient structure, comprised of lens precursor cells, is polarized with its anterior cells retaining their epithelial morphology and proliferative capacity, whereas the posterior lens precursor cells initiate terminal differentiation forming the primary lens fibers. Lens differentiation is marked by expression and accumulation of crystallins and other structural proteins. The transcriptional control of crystallin genes is characterized by the reiterative use of transcription factors required for the establishment of lens precursors in combination with more ubiquitously expressed factors (e.g. AP-1, AP-2alpha, CREB and USF) and recruitment of histone acetyltransferases (HATs) CBP and p300, and chromatin remodeling complexes SWI/SNF and ISWI. These studies have poised the study of lens development at the forefront of efforts to understand the connections between development, cell signaling, gene transcription and chromatin remodeling.

PMID: 17905638

Lens induction in vertebrates: variations on a conserved theme of signaling events

Donner AL, Lachke SA, Maas RL. Semin Cell Dev Biol. 2006 Dec;17(6):676-85. Epub 2006 Oct 27. Review. PMID: 17164096

Growth factor regulation of lens development

Lovicu FJ, McAvoy JW. Dev Biol. 2005 Apr 1;280(1):1-14. Review. PMID: 15766743

PMID: 18782574

A network of capillaries branches from the hyaloid vascular system and surrounds the mammalian lens throughout much of its embryonic development. These vessels are presumed to be important for the growth and maturation of the lens, although the lenses of non-mammalian vertebrates have no comparable vessels.

PMID: 8641842