Fibroblast growth factor (FGF) signaling is an essential regulator of lens epithelial cell proliferation and survival, as well as lens fiber cell differentiation. However, the identities of these FGF factors, their source tissue and the genes that regulate their synthesis are unknown. We have found that Chx10-Cre;Lhx2lox/lox mice, which selectively lack Lhx2 expression in neuroretina from E10.5, showed an early arrest in lens fiber development along with severe microphthalmia. These mutant animals showed reduced expression of multiple neuroretina-expressed FGFs and canonical FGF-regulated genes in neuroretina. When FGF expression was genetically restored in Lhx2-deficient neuroretina of Chx10-Cre;Lhx2lox/lox mice, we observed a partial but nonetheless substantial rescue of the defects in lens cell proliferation, survival and fiber differentiation. These data demonstrate that neuroretinal expression of Lhx2 and neuroretina-derived FGF factors are crucial for lens fiber development in vivo.
The authors declare no competing or financial interests.
Conceptulalization: T.T., J.d.M. and S.B.; Methodology: T.T., J.d.M., C.Z., B.S.C., F.J. and S.B.; Investigation: T.T., J.d.M., C.Z., B.S.C. and S.B.; Writing – Original Draft: T.T and S.B.; Writing – Review and Editing: T.T., J.d.M., C.Z., B.S.C. and S.B. Funding Acquisition: J.d.M. and S.B.; Resources: S.B.; Supervision: S.B.
This work was supported by the National Institutes of Health [R01EY020560 and R01EY017015 to S.B and F32EY024201 to B.S.C], by a grant from the Knights Templar Eye Foundation (to J.d.M.). S.B. was awarded a W. M. Keck Distinguished Young Scholar in Medical Research. Deposited in PMC for release after 12 months.
Supplementary information available online at http://dev.biologists.org/lookup/doi/10.1242/dev.137760.supplemental
- Received March 17, 2016.
- Accepted September 1, 2016.