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 Beisel, Bernd Fritzsch

Research output: Contribution to journalArticle

29 Citations (Scopus)

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.

Original languageEnglish
Article numbere30853
JournalPLoS One
Volume7
Issue number1
DOIs
StatePublished - Jan 24 2012

Fingerprint

Organ of Corti
cell viability
Cell Survival
Cells
hairs
Neurons
cells
neurons
Plasticity
mice
Nerve Growth Factors
Gene expression
Stereocilia
Haploinsufficiency
mutants
Cell Polarity
Transcription Factors
neurotrophins
Genes
Inner Ear

All Science Journal Classification (ASJC) codes

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Jahan, I., Pan, N., Kersigo, J., Calisto, L. E., Morris, K. A., Kopecky, B., ... Fritzsch, B. (2012). Expression of Neurog1 instead of Atoh1 can partially rescue organ of Corti cell survival. PLoS One, 7(1), [e30853]. https://doi.org/10.1371/journal.pone.0030853

Expression of Neurog1 instead of Atoh1 can partially rescue organ of Corti cell survival. / Jahan, Israt; Pan, Ning; Kersigo, Jennifer; Calisto, Lilian E.; Morris, Ken A.; Kopecky, Benjamin; Duncan, Jeremy S.; Beisel, Kirk; Fritzsch, Bernd.

In: PLoS One, Vol. 7, No. 1, e30853, 24.01.2012.

Research output: Contribution to journalArticle

Jahan, I, Pan, N, Kersigo, J, Calisto, LE, Morris, KA, Kopecky, B, Duncan, JS, Beisel, K & Fritzsch, B 2012, 'Expression of Neurog1 instead of Atoh1 can partially rescue organ of Corti cell survival', PLoS One, vol. 7, no. 1, e30853. https://doi.org/10.1371/journal.pone.0030853
Jahan I, Pan N, Kersigo J, Calisto LE, Morris KA, Kopecky B et al. Expression of Neurog1 instead of Atoh1 can partially rescue organ of Corti cell survival. PLoS One. 2012 Jan 24;7(1). e30853. https://doi.org/10.1371/journal.pone.0030853
Jahan, Israt ; Pan, Ning ; Kersigo, Jennifer ; Calisto, Lilian E. ; Morris, Ken A. ; Kopecky, Benjamin ; Duncan, Jeremy S. ; Beisel, Kirk ; Fritzsch, Bernd. / Expression of Neurog1 instead of Atoh1 can partially rescue organ of Corti cell survival. In: PLoS One. 2012 ; Vol. 7, No. 1.
@article{b1745ca7dfca43eab47c4cdead71988d,
title = "Expression of Neurog1 instead of Atoh1 can partially rescue organ of Corti cell survival",
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.",
author = "Israt Jahan and Ning Pan and Jennifer Kersigo and Calisto, {Lilian E.} and Morris, {Ken A.} and Benjamin Kopecky and Duncan, {Jeremy S.} and Kirk Beisel and Bernd Fritzsch",
year = "2012",
month = "1",
day = "24",
doi = "10.1371/journal.pone.0030853",
language = "English",
volume = "7",
journal = "PLoS One",
issn = "1932-6203",
publisher = "Public Library of Science",
number = "1",

}

TY - JOUR

T1 - Expression of Neurog1 instead of Atoh1 can partially rescue organ of Corti cell survival

AU - Jahan, Israt

AU - Pan, Ning

AU - Kersigo, Jennifer

AU - Calisto, Lilian E.

AU - Morris, Ken A.

AU - Kopecky, Benjamin

AU - Duncan, Jeremy S.

AU - Beisel, Kirk

AU - Fritzsch, Bernd

PY - 2012/1/24

Y1 - 2012/1/24

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84856200842&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84856200842&partnerID=8YFLogxK

U2 - 10.1371/journal.pone.0030853

DO - 10.1371/journal.pone.0030853

M3 - Article

VL - 7

JO - PLoS One

JF - PLoS One

SN - 1932-6203

IS - 1

M1 - e30853

ER -