Journal Article

Lens induction requires attenuation of ERK signaling by <i>Nf1</i>

Christian Carbe and Xin Zhang

in Human Molecular Genetics

Volume 20, issue 7, pages 1315-1323
Published in print April 2011 | ISSN: 0964-6906
Published online January 2011 | e-ISSN: 1460-2083 | DOI: http://dx.doi.org/10.1093/hmg/ddr014
Lens induction requires attenuation of ERK signaling by Nf1

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Aphakia (lack of lens) is a rare human congenital disorder with its genetic etiology largely unknown. Even in model organisms, very few mutations are known to result in such a drastic ocular defect. In this study, we have shown that homozygous deletion of Nf1, the Ras GTPase gene underlying human neurofibromatosis type 1 syndrome, causes lens dysgenesis in mouse. Although early lens specification proceeded normally in Nf1 mutants, lens induction was disrupted due to deficient cell proliferation. Further analysis showed that extracellular signal-regulated kinase (ERK) signaling was initially elevated in the invaginating lens placode, but by the lens vesicle stage, ERK phosphorylation was significantly reduced. Only after intraperitoneal treatment of U0126, an inhibitor of ERK phosphorylation, was lens development restored in Nf1 mutants. Hyperactive Ras-mitogen-activated protein kinase (MAPK) signaling is known to cause neuro-cardiofacial-cutaneous (NCFC) syndromes in humans. As a member of NCFC family genes, Nf1 represents the first example that attenuation of Ras-MAPK kinase signaling pathway is essential for normal lens development.

Journal Article.  4278 words.  Illustrated.

Subjects: Genetics and Genomics

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