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Biology Articles » Developmental Biology » A crucial role for TGFbeta signaling in congenital eye disorders

A crucial role for TGFbeta signaling in congenital eye disorders

December 14, 2005 -- The lens in the developing eye acts as a TGFbeta signaling center that controls differentiation, survival and formation of multiple eye structures deriving from the neural crest. A study published today in the open access journal Journal of Biology shows that neural crest (NC) derived cells contribute to both anterior and posterior parts of the developing mammalian eye. NC cells migrate properly in the eye but fail to differentiate in the absence of TGFbeta signaling. The activity of TGFbeta is mediated by the two transcription factors Foxc1 and Pitx2 that have been implicated in human eye disorders. These findings shed light on the origin of congenital eye disorders that can give rise to glaucoma and blindness: Axenfeld-Rieger's anomaly and persistent hyperplastic primary vitreous.

Lukas Sommer, from the Institute of Cell Biology at the ETH in Zurich, Switzerland, heading an international team including Lars Ittner, used in vivo cell fate mapping in mice. They show that NC-derived cells can be found in the eye vesicle of mouse embryos, soon after it is formed. NC-derived cells subsequently contribute to various structures of the developing eye, and Ittner et al. show for the first time an NC contribution to the primary vitreous.

TGFbeta receptor type 2, Tgfbr2, was inactivated to study the importance of the signaling pathway in NC-derived cells. In these mice, the eyes were reduced in size and the lens and cornea failed to separate. The authors show that TGFbeta signaling is crucial for proper differentiation and morphogenesis of NC-derived cells in eye structures. Conceivably, TGFbeta might be able to support differentiation not only during eye development but also at later stages. If so, this might open up new strategies for promoting regeneration of eye structures, for example in patients suffering from loss of corneal transparency.

Source : BioMed Central


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