BACKGROUND: Specific molecules involved in early inductive signaling from anterior neural tissue to the placodal ectoderm to establish a lens-forming bias, as well as their regulatory factors, remain largely unknown. In this study, we sought to identify and characterize these molecules. RESULTS: Using an expression cloning strategy to isolate genes with lens-inducing activity, we identified the transcriptional cofactor ldb1. This, together with evidence for its nuclear dependence, suggests its role as a regulatory factor, not a direct signaling molecule. We propose that ldb1 mediates induction of early lens genes in our functional assay by transcriptional activation of lens-inducing signals. Gain-of-function assays demonstrate that the inductive activity of the anterior neural plate on head ectodermal structures can be augmented by ldb1. Loss-of-function assays show that knockdown of ldb1 leads to decreased expression of early lens and retinal markers and subsequently to defects in eye development. CONCLUSIONS: The functional cloning, expression pattern, overexpression, and knockdown data show that an ldb1-regulated mechanism acts as an early signal for Xenopus lens induction.
BACKGROUND: Specific molecules involved in early inductive signaling from anterior neural tissue to the placodal ectoderm to establish a lens-forming bias, as well as their regulatory factors, remain largely unknown. In this study, we sought to identify and characterize these molecules. RESULTS: Using an expression cloning strategy to isolate genes with lens-inducing activity, we identified the transcriptional cofactor ldb1. This, together with evidence for its nuclear dependence, suggests its role as a regulatory factor, not a direct signaling molecule. We propose that ldb1 mediates induction of early lens genes in our functional assay by transcriptional activation of lens-inducing signals. Gain-of-function assays demonstrate that the inductive activity of the anterior neural plate on head ectodermal structures can be augmented by ldb1. Loss-of-function assays show that knockdown of ldb1 leads to decreased expression of early lens and retinal markers and subsequently to defects in eye development. CONCLUSIONS: The functional cloning, expression pattern, overexpression, and knockdown data show that an ldb1-regulated mechanism acts as an early signal for Xenopus lens induction.
Authors: Cenap Güngör; Naoko Taniguchi-Ishigaki; Hong Ma; Alexander Drung; Baris Tursun; Heather P Ostendorff; Michael Bossenz; Catherina G Becker; Thomas Becker; Ingolf Bach Journal: Proc Natl Acad Sci U S A Date: 2007-09-11 Impact factor: 11.205