Expression of Neurog1 instead of Atoh1 can partially rescue organ of Corti cell survival

Israt Jahan; Ning Pan; Jennifer Kersigo; Lilian E Calisto; Ken A Morris; Benjamin Kopecky; Jeremy S Duncan; Kirk W Beisel; Bernd Fritzsch

doi:10.1371/journal.pone.0030853

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Expression of Neurog1 instead of Atoh1 can partially rescue organ of Corti cell survival

Journal article

Open access

Peer reviewed

Expression of Neurog1 instead of Atoh1 can partially rescue organ of Corti cell survival

Israt Jahan, Ning Pan, Jennifer Kersigo, Lilian E Calisto, Ken A Morris, Benjamin Kopecky, Jeremy S Duncan, Kirk W Beisel and Bernd Fritzsch

PloS one, Vol.7(1), pp.e30853-e30853

2012

DOI: 10.1371/journal.pone.0030853

PMCID: PMC3265522

PMID: 22292060

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Abstract

In the mammalian inner ear neurosensory cell fate depends on three closely related transcription factors, Atoh1 for hair cells and Neurog1 and Neurod1 for neurons. We have previously shown that neuronal cell fate can be altered towards hair cell fate by eliminating Neurod1 mediated repression of Atoh1 expression in neurons. To test whether a similar plasticity is present in hair cell fate commitment, we have generated a knockin (KI) mouse line (Atoh1(KINeurog1)) in which Atoh1 is replaced by Neurog1. Expression of Neurog1 under Atoh1 promoter control alters the cellular gene expression pattern, differentiation and survival of hair cell precursors in both heterozygous (Atoh1(+/KINeurog1)) and homozygous (Atoh1(KINeurog1/KINeurog1)) KI mice. Homozygous KI mice develop patches of organ of Corti precursor cells that express Neurog1, Neurod1, several prosensory genes and neurotrophins. In addition, these patches of cells receive afferent and efferent processes. Some cells among these patches form multiple microvilli but no stereocilia. Importantly, Neurog1 expressing mutants differ from Atoh1 null mutants, as they have intermittent formation of organ of Corti-like patches, opposed to a complete 'flat epithelium' in the absence of Atoh1. In heterozygous KI mice co-expression of Atoh1 and Neurog1 results in change in fate and patterning of some hair cells and supporting cells in addition to the abnormal hair cell polarity in the later stages of development. This differs from haploinsufficiency of Atoh1 (Pax2cre; Atoh1(f/+)), indicating the effect of Neurog1 expression in developing hair cells. Our data suggest that Atoh1(KINeurog1) can provide some degree of functional support for survival of organ of Corti cells. In contrast to the previously demonstrated fate plasticity of neurons to differentiate as hair cells, hair cell precursors can be maintained for a limited time by Neurog1 but do not transdifferentiate as neurons.

Hair Cells, Auditory - cytology

Hair Cells, Auditory - metabolism

Organ of Corti - embryology

Embryo, Mammalian

Cell Survival - genetics

Organ of Corti - physiology

Basic Helix-Loop-Helix Transcription Factors - metabolism

Hair Cells, Auditory - physiology

Gene Expression Regulation, Developmental

Female

Basic Helix-Loop-Helix Transcription Factors - physiology

Nerve Tissue Proteins - physiology

Basic Helix-Loop-Helix Transcription Factors - genetics

Cells, Cultured

Mice, Transgenic

Nerve Tissue Proteins - genetics

Gene Knock-In Techniques

Nerve Tissue Proteins - metabolism

Pregnancy

Animals

Organogenesis - genetics

Genes, Lethal - genetics

Organ of Corti - cytology

Mice

Organ of Corti - metabolism

Details

Title: Subtitle: Expression of Neurog1 instead of Atoh1 can partially rescue organ of Corti cell survival
Creators: Israt Jahan - University of Iowa, Department of Biology, Iowa City, Iowa, United States of America
Ning Pan
Jennifer Kersigo
Lilian E Calisto
Ken A Morris
Benjamin Kopecky
Jeremy S Duncan
Kirk W Beisel
Bernd Fritzsch
Resource Type: Journal article
Publication Details: PloS one, Vol.7(1), pp.e30853-e30853
DOI: 10.1371/journal.pone.0030853
PMID: 22292060
PMCID: PMC3265522
NLM abbreviation: PLoS One
ISSN: 1932-6203
eISSN: 1932-6203
Publisher: Public Library of Science; United States
Grant note: R01 S1 DC 005590 / NIDCD NIH HHS P30 DC 010362 / NIDCD NIH HHS R01 DC005590 / NIDCD NIH HHS T32 GM007337 / NIGMS NIH HHS P30 DC010362 / NIDCD NIH HHS R01 DC 005590 / NIDCD NIH HHS
Language: English
Date published: 2012
Academic Unit: Iowa Neuroscience Institute; Biology; Craniofacial Anomalies Research Center
Record Identifier: 9984070278302771

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