Scholars@Duke publication: Ankyrin-G regulated epithelial phenotype is required for mouse lens morphogenesis and growth.

Ankyrin-G regulated epithelial phenotype is required for mouse lens morphogenesis and growth.

Publication , Journal Article

Rasiah, PK; Maddala, R; Bennett, V; Rao, PV

Published in: Dev Biol

February 1, 2019

Epithelial cell polarity, adhesion, proliferation, differentiation and survival are essential for morphogenesis of various organs and tissues including the ocular lens. The molecular mechanisms regulating the lens epithelial phenotype however, are not well understood. Here we investigated the role of scaffolding protein ankyrin-G (AnkG) in mouse lens development by conditional suppression of AnkG expression using the Cre-LoxP recombination approach. AnkG, which serves to link integral membrane proteins to the spectrin/actin cytoskeleton, was found to distribute predominantly to the lateral membranes of lens epithelium with several isoforms of the protein being detected in the mouse lens. Conditional deficiency of AnkG impaired mouse lens morphogenesis starting from embryonic stage E15.5, with neonatal (P1) AnkG cKO lenses exhibiting overt abnormalities in shape, size, epithelial cell height, sheet length and lateral membrane assembly together with defective fiber cell orientation relative to lenses from littermate AnkG floxed or Cre expressing mice. Severe disruptions in E-cadherin/β-catenin-based adherens junctions, and the membrane organization of spectrin-actin cytoskeleton, ZO-1, connexin-50 and Na+-K+-ATPase were noted in AnkG deficient lenses, along with detection in lens epithelium of α-smooth muscle actin, a marker of epithelial to mesenchymal transition. Moreover, lens epithelial cell proliferation and survival were severely compromised while differentiation appears to be normal in AnkG deficient mouse lenses. Collectively, these results indicate that AnkG regulates establishment of the epithelial phenotype via lateral membrane assembly, stabilization of E-cadherin-based cell-cell junctions, polarity and membrane organization of transport and adhesion proteins and the spectrin-actin skeleton, and provide evidence for an obligatory role for AnkG in lens morphogenesis and growth.

Duke Scholars

Author Rupalatha Maddala Ophthalmology

Author Vann Bennett Biochemistry

Author Ponugoti Vasantha Rao Ophthalmology, Glaucoma

Published In

Dev Biol

DOI

10.1016/j.ydbio.2018.12.016

EISSN

1095-564X

Publication Date

February 1, 2019

Volume

446

Issue

Start / End Page

119 / 131

Location

United States

Related Subject Headings

Phenotype
Morphogenesis
Mice, Transgenic
Mice, Knockout
Mice, Inbred C57BL
Lens, Crystalline
Gene Expression Regulation, Developmental
Epithelium
Epithelial-Mesenchymal Transition
Epithelial Cells

Citation

APA

Chicago

ICMJE

MLA

NLM

Rasiah, P. K., Maddala, R., Bennett, V., & Rao, P. V. (2019). Ankyrin-G regulated epithelial phenotype is required for mouse lens morphogenesis and growth. Dev Biol, 446(1), 119–131. https://doi.org/10.1016/j.ydbio.2018.12.016

Rasiah, Pratheepa Kumari, Rupalatha Maddala, Vann Bennett, and Ponugoti Vasantha Rao. “Ankyrin-G regulated epithelial phenotype is required for mouse lens morphogenesis and growth.” Dev Biol 446, no. 1 (February 1, 2019): 119–31. https://doi.org/10.1016/j.ydbio.2018.12.016.

Rasiah PK, Maddala R, Bennett V, Rao PV. Ankyrin-G regulated epithelial phenotype is required for mouse lens morphogenesis and growth. Dev Biol. 2019 Feb 1;446(1):119–31.

Rasiah, Pratheepa Kumari, et al. “Ankyrin-G regulated epithelial phenotype is required for mouse lens morphogenesis and growth.” Dev Biol, vol. 446, no. 1, Feb. 2019, pp. 119–31. Pubmed, doi:10.1016/j.ydbio.2018.12.016.

Rasiah PK, Maddala R, Bennett V, Rao PV. Ankyrin-G regulated epithelial phenotype is required for mouse lens morphogenesis and growth. Dev Biol. 2019 Feb 1;446(1):119–131.