Notch signaling regulates growth and differentiation in the mammalian lens

Sheldon Rowan, Kevin W. Conley, Tien T. Le, Amy L. Donner, Richard L. Maas, Nadean L Brown

Research output: Contribution to journalArticle

76 Citations (Scopus)

Abstract

The Notch signal transduction pathway regulates the decision to proliferate versus differentiate. Although there are a myriad of mouse models for the Notch pathway, surprisingly little is known about how these genes regulate early eye development, particularly in the anterior lens. We employed both gain-of-function and loss-of-function approaches to determine the role of Notch signaling in lens development. Here we analyzed mice containing conditional deletion of the Notch effector Rbpj or overexpression of the activated Notch1 intracellular domain during lens formation. We demonstrate distinct functions for Notch signaling in progenitor cell growth, fiber cell differentiation and maintenance of the transition zone. In particular, Notch signaling controls the timing of primary fiber cell differentiation and is essential for secondary fiber cell differentiation. Either gain or loss of Notch signaling leads to formation of a dysgenic lens, which in loss-of-function mice undergoes a profound postnatal degeneration. Our data suggest both Cyclin D1 and Cyclin D2, and the p27Kip1 cyclin-dependent kinase inhibitor act downstream of Notch signaling, and define multiple critical functions for this pathway during lens development.

Original languageEnglish (US)
Pages (from-to)111-122
Number of pages12
JournalDevelopmental Biology
Volume321
Issue number1
DOIs
StatePublished - Sep 1 2008
Externally publishedYes

Fingerprint

Lenses
Growth
Cell Differentiation
Cyclin D2
Critical Pathways
Cyclin-Dependent Kinases
Cyclin D1
Signal Transduction
Stem Cells
Maintenance
Genes

Keywords

  • Activated Notch
  • CKI
  • Cyclins
  • Growth
  • Lens development
  • Notch signaling
  • Rbpj

ASJC Scopus subject areas

  • Developmental Biology

Cite this

Notch signaling regulates growth and differentiation in the mammalian lens. / Rowan, Sheldon; Conley, Kevin W.; Le, Tien T.; Donner, Amy L.; Maas, Richard L.; Brown, Nadean L.

In: Developmental Biology, Vol. 321, No. 1, 01.09.2008, p. 111-122.

Research output: Contribution to journalArticle

Rowan, Sheldon ; Conley, Kevin W. ; Le, Tien T. ; Donner, Amy L. ; Maas, Richard L. ; Brown, Nadean L. / Notch signaling regulates growth and differentiation in the mammalian lens. In: Developmental Biology. 2008 ; Vol. 321, No. 1. pp. 111-122.
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