Chx10 is required to block photoreceptor differentiation but is dispensable for progenitor proliferation in the postnatal retina

Izzy Livne-Bar, Marek Pacal, Melissa C. Cheung, Mark Hankin, Judy Trogadis, Danian Chen, Kimberley M. Dorval, Rod Bremner

Research output: Contribution to journalArticle

57 Citations (Scopus)

Abstract

In the Chx10-null ocular retardation (orJ) mouse, retinal progenitor cell (RPC) proliferation is impaired, and bipolar neurons, a late born cell type, fail to differentiate. It is unclear whether Chx10 is required to maintain proliferation throughout retinogenesis or whether the bipolar cell defect is an indirect effect of growth arrest. We show that Chx10 is dispensable for late-stage RPC proliferation but is essential to promote bipolar cell genesis in place of rods. Ectopic Chx10 expression drove bipolar instead of rod cell differentiation without affecting division. Converting Chx10 to an activator impaired bipolar cell differentiation, implying that repression is important for Chx10 activity. In the Chx10 null orJ retina, only a small fraction of cells expressing mutated Chx10 mRNA were rods, but this fraction increased after p27Kip1 inactivation, which partially rescues proliferation. Most significantly, acute Chx10 knockdown in the postnatal retina promoted rods in place of bipolar neurons without affecting division. Thus, Chx10 directly controls bipolar cell genesis by inhibiting rod differentiation independent of its temporally limited early effect on RPC proliferation.

Original languageEnglish (US)
Pages (from-to)4988-4993
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume103
Issue number13
DOIs
StatePublished - Mar 28 2006
Externally publishedYes

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Retina
Stem Cells
Cell Proliferation
Cell Differentiation
Retinal Rod Photoreceptor Cells
Neurons
Messenger RNA
Growth

Keywords

  • CVC domain
  • Homeobox
  • Homeodomain
  • Short-hairpin RNA

ASJC Scopus subject areas

  • General

Cite this

Chx10 is required to block photoreceptor differentiation but is dispensable for progenitor proliferation in the postnatal retina. / Livne-Bar, Izzy; Pacal, Marek; Cheung, Melissa C.; Hankin, Mark; Trogadis, Judy; Chen, Danian; Dorval, Kimberley M.; Bremner, Rod.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 103, No. 13, 28.03.2006, p. 4988-4993.

Research output: Contribution to journalArticle

Livne-Bar, Izzy ; Pacal, Marek ; Cheung, Melissa C. ; Hankin, Mark ; Trogadis, Judy ; Chen, Danian ; Dorval, Kimberley M. ; Bremner, Rod. / Chx10 is required to block photoreceptor differentiation but is dispensable for progenitor proliferation in the postnatal retina. In: Proceedings of the National Academy of Sciences of the United States of America. 2006 ; Vol. 103, No. 13. pp. 4988-4993.
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