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The Dkk1 dose is critical for eye development

Lieven, Oliver LU and Ruether, Ulrich (2011) In Developmental Biology 355(1). p.124-137
Abstract
During mammalian ocular development, several signaling pathways control the spatiotemporal highly defined realization of the three-dimensional eye architecture. Given the complexity of these inductive signals, the developing eye is a sensitive organ for several diseases. In this study, we investigated a Dkk1+/- haploinsufficiency during eye development, resulting in coloboma and anterior eye defects, two common developmental eye disorders. Dkk1 impacts eye development from a defined developmental time point on, and is critical for lens separation from the surface ectoderm via beta-catenin mediated Pdgfr alpha and E-cadherin expression. Dkk1 does not impact the dorso ventral retina patterning in general but is critical for Shh dependent... (More)
During mammalian ocular development, several signaling pathways control the spatiotemporal highly defined realization of the three-dimensional eye architecture. Given the complexity of these inductive signals, the developing eye is a sensitive organ for several diseases. In this study, we investigated a Dkk1+/- haploinsufficiency during eye development, resulting in coloboma and anterior eye defects, two common developmental eye disorders. Dkk1 impacts eye development from a defined developmental time point on, and is critical for lens separation from the surface ectoderm via beta-catenin mediated Pdgfr alpha and E-cadherin expression. Dkk1 does not impact the dorso ventral retina patterning in general but is critical for Shh dependent Pax2 extension into the midline region. The described results also indicate that the retinal Dkk1 dose is critical for important steps during eye development, such as optic fissure closure and cornea formation. Further analysis of the relationship between Dkk1 and Shh signaling revealed that Dkk1 and Shh coordinatively control anterior head formation and eye induction. During eye development itself, retinal Dkk1 activation is depending on cilia mediated Gli3 regulation. Therefore, our data essentially improve the knowledge of coloboma and anterior eye defects, which are common human eye developmental defects. (C) 2011 Elsevier Inc. All rights reserved. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Eye development, Dkk1, Coloboma, Wnt signaling, beta-catenin, Lens, development
in
Developmental Biology
volume
355
issue
1
pages
124 - 137
publisher
Elsevier
external identifiers
  • wos:000291454000012
  • scopus:79957625026
ISSN
1095-564X
DOI
10.1016/j.ydbio.2011.04.023
language
English
LU publication?
yes
id
7f45f496-08c4-42d3-a1a0-e54c2c582daa (old id 1984982)
date added to LUP
2011-07-01 09:11:51
date last changed
2017-09-03 03:24:38
@article{7f45f496-08c4-42d3-a1a0-e54c2c582daa,
  abstract     = {During mammalian ocular development, several signaling pathways control the spatiotemporal highly defined realization of the three-dimensional eye architecture. Given the complexity of these inductive signals, the developing eye is a sensitive organ for several diseases. In this study, we investigated a Dkk1+/- haploinsufficiency during eye development, resulting in coloboma and anterior eye defects, two common developmental eye disorders. Dkk1 impacts eye development from a defined developmental time point on, and is critical for lens separation from the surface ectoderm via beta-catenin mediated Pdgfr alpha and E-cadherin expression. Dkk1 does not impact the dorso ventral retina patterning in general but is critical for Shh dependent Pax2 extension into the midline region. The described results also indicate that the retinal Dkk1 dose is critical for important steps during eye development, such as optic fissure closure and cornea formation. Further analysis of the relationship between Dkk1 and Shh signaling revealed that Dkk1 and Shh coordinatively control anterior head formation and eye induction. During eye development itself, retinal Dkk1 activation is depending on cilia mediated Gli3 regulation. Therefore, our data essentially improve the knowledge of coloboma and anterior eye defects, which are common human eye developmental defects. (C) 2011 Elsevier Inc. All rights reserved.},
  author       = {Lieven, Oliver and Ruether, Ulrich},
  issn         = {1095-564X},
  keyword      = {Eye development,Dkk1,Coloboma,Wnt signaling,beta-catenin,Lens,development},
  language     = {eng},
  number       = {1},
  pages        = {124--137},
  publisher    = {Elsevier},
  series       = {Developmental Biology},
  title        = {The Dkk1 dose is critical for eye development},
  url          = {http://dx.doi.org/10.1016/j.ydbio.2011.04.023},
  volume       = {355},
  year         = {2011},
}