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Analysis of aPKClambda and aPKCzeta reveals multiple and redundant functions during vertebrate retinogenesis.

ABSTRACT: Retinal lamination is known to depend on cell polarity and localized signaling. In vertebrates, atypical protein kinase C proteins, aPKClambda/iota and aPKCzeta, are essential for apical-basal cell polarity. However, it is not known to what extent functional redundancy has precluded a comprehensive functional characterization of aPKC signaling during vertebrate retinogenesis. Here, we show that aPKCs lambda and zeta are functionally redundant for multiple aspects of retinogenesis including mitotic division location and orientation, cell-type positioning, and retinal pigment epithelial (RPE) and photoreceptor cell morphogenesis. Genetic mosaic analyses demonstrate a cell-autonomous requirement of aPKCs for RPE and photoreceptor development, and a cell-non-cell-autonomous function that is intrinsic to the neural retina for cell-type positioning. Our observations uncover a previously unappreciated involvement of aPKCzeta during zebrafish retinogenesis and suggest that aPKC signaling primes the retinal environment for appropriate cell migration of post-mitotic progenitor cells but is not essential for correct cell-type specification.

SUBMITTER: Cui S

PROVIDER: S-EPMC2700298 | biostudies-literature | 2007 Mar

REPOSITORIES: biostudies-literature

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Analysis of aPKClambda and aPKCzeta reveals multiple and redundant functions during vertebrate retinogenesis.

Cui Shuang S Otten Cécile C Rohr Stefan S Abdelilah-Seyfried Salim S Link Brian A BA

Molecular and cellular neurosciences 20070112 3

Retinal lamination is known to depend on cell polarity and localized signaling. In vertebrates, atypical protein kinase C proteins, aPKClambda/iota and aPKCzeta, are essential for apical-basal cell polarity. However, it is not known to what extent functional redundancy has precluded a comprehensive functional characterization of aPKC signaling during vertebrate retinogenesis. Here, we show that aPKCs lambda and zeta are functionally redundant for multiple aspects of retinogenesis including mitot ...[more]

PMID: 17223574

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Project description:Lrig proteins are conserved transmembrane proteins that modulate a variety of signaling pathways from worm to humans. In mammals, there are three family members - Lrig1, Lrig2, and Lrig3--that are defined by closely related extracellular domains with a similar arrangement of leucine rich repeats and immunoglobulin domains. However, the intracellular domains show little homology. Lrig1 inhibits EGF signaling through internalization and degradation of ErbB receptors. Although Lrig3 can also bind ErbB receptors in vitro, it is unclear whether Lrig2 and Lrig3 exhibit similar functions to Lrig1. To gain insights into Lrig gene functions in vivo, we compared the expression and function of the Lrigs in the inner ear, which offers a sensitive system for detecting effects on morphogenesis and function. We find that all three family members are expressed in the inner ear throughout development, with Lrig1 and Lrig3 restricted to subsets of cells and Lrig2 expressed more broadly. Lrig1 and Lrig3 overlap prominently in the developing vestibular apparatus and simultaneous removal of both genes disrupts inner ear morphogenesis. This suggests that these two family members act redundantly in the otic epithelium. In contrast, although Lrig1 and Lrig2 are frequently co-expressed, Lrig1(-/-);Lrig2(-/-) double mutant ears show no enhanced structural abnormalities. At later stages, Lrig1 expression is sustained in non-sensory tissues, whereas Lrig2 levels are enhanced in neurons and sensory epithelia. Consistent with these distinct expression patterns, Lrig1 and Lrig2 mutant mice exhibit different forms of impaired auditory responsiveness. Notably, Lrig1(-/-);Lrig2(-/-) double mutant mice display vestibular deficits and suffer from a more severe auditory defect that is accompanied by a cochlear innervation phenotype not present in single mutants. Thus, Lrig genes appear to act both redundantly and independently, with Lrig2 emerging as the most functionally distinct family member.

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Dataset Information

Analysis of aPKClambda and aPKCzeta reveals multiple and redundant functions during vertebrate retinogenesis.

Publications

Analysis of aPKClambda and aPKCzeta reveals multiple and redundant functions during vertebrate retinogenesis.

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