Regulation of retinal progenitor expansion by Frizzled receptors: implications for microphthalmia and retinal coloboma

Chunqiao Liu; Hirva Bakeri; Tiansen Li; Anand Swaroop

doi:10.1093/hmg/ddr616

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Regulation of retinal progenitor expansion by Frizzled receptors: implications for microphthalmia and retinal coloboma

Journal article

Open access

Peer reviewed

Regulation of retinal progenitor expansion by Frizzled receptors: implications for microphthalmia and retinal coloboma

Chunqiao Liu, Hirva Bakeri, Tiansen Li and Anand Swaroop

Human molecular genetics, Vol.21(8), pp.1848-1860

04/15/2012

DOI: 10.1093/hmg/ddr616

PMCID: PMC3313798

PMID: 22228100

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Abstract

Nineteen Wnt ligands and 10 Frizzled (Fz) receptors mediate multiple distinct cellular events during neuronal development. However, their precise roles in cell-type specification and organogenesis are poorly delineated because of overlapping functions and expression profiles. Here, we have explored the role of two closely related Frizzled receptors, Fz5 and Fz8, in mouse retinal development. We previously showed that Fz5(-/-) mice exhibit mild coloboma and microphthalmia at ~50% penetrance. Fz8 expression overlaps with Fz5 in the neural retina and optic fissure/disc. Mice lacking Fz8 show minimal eye and retinal defects. The embryos lacking both Fz5 and Fz8 die early in development, but a majority of triallelic Fz5(-/-);Fz8(+/-) mutants survive until birth. The triallelic mutant develops severe retinal coloboma and microphthalmia with full penetrance. At the cellular level, impaired neurogenesis is indicated by increased early-born retinal neurons that result from accelerated cell cycle exit of progenitors. Deficiency of apical retinal neuroepithelium is indicated by altered localization of apical junction markers, such as atypical protein kinase C, RhoA and β-catenin. Hes1 expression, which is critical for retinal progenitor expansion, is down-regulated in the triallelic mutant mouse. Furthermore, blocking Frizzled receptors in cultured retinal explants led to basally shifted divisions of retinal progenitors. Together, our studies suggest a dose-dependent regulation of signaling by Fz5 and Fz8 in optic fissure/disc formation and progenitor expansion.

Retina - metabolism

Microphthalmos - genetics

Mitosis

Coloboma - genetics

Axons - physiology

Microphthalmos - metabolism

Retina - embryology

Neural Stem Cells - cytology

Neurogenesis

Retinal Neurons - cytology

Optic Disk - embryology

Gene Expression Regulation, Developmental

Optic Disk - metabolism

Receptors, G-Protein-Coupled - physiology

Gliosis - genetics

Signal Transduction

rho GTP-Binding Proteins - genetics

Down-Regulation

Gliosis - metabolism

Neural Stem Cells - physiology

Frizzled Receptors - physiology

beta Catenin - metabolism

beta Catenin - genetics

Mice, Knockout

Animals

Frizzled Receptors - genetics

rho GTP-Binding Proteins - metabolism

Mice

Receptors, G-Protein-Coupled - genetics

Coloboma - metabolism

Mutation

Retinal Neurons - physiology

Details

Title: Subtitle: Regulation of retinal progenitor expansion by Frizzled receptors: implications for microphthalmia and retinal coloboma
Creators: Chunqiao Liu - Neurobiology Neurodegeneration and Repair Laboratory, National Eye Institute, Bethesda, MD 20892, USA. cqliu@nei.nih.gov
Hirva Bakeri
Tiansen Li
Anand Swaroop
Resource Type: Journal article
Publication Details: Human molecular genetics, Vol.21(8), pp.1848-1860
DOI: 10.1093/hmg/ddr616
PMID: 22228100
PMCID: PMC3313798
ISSN: 0964-6906
eISSN: 1460-2083
Grant note: Intramural NIH HHS
Language: English
Date published: 04/15/2012
Academic Unit: General Internal Medicine; Internal Medicine
Record Identifier: 9984094559802771

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