Which signaling molecule is required for lens differentiation and activates Sox2?
BMP4 expressed in optic vesicle and periocular mesenchyme plays biphasic roles in lens specification. Early BMP4 activates Smad-dependent transcription of Sox2 in head ectoderm that already expresses Pax6, allowing formation of Pax6-Sox2 complex on delta-crystallin enhancer. This triggers lens placode thickening and invagination. Later BMP activity must be attenuated by Noggin in neural retina to permit differentiation. Conditional deletion of Bmpr1a in mouse surface ectoderm abolishes Sox2 upregulation and lens vesicle formation, while exogenous BMP beads rescue competence, confirming require
Ref: Gilbert, Developmental Biology, 12th ed., Chapter 7: BMP signaling in lens induction and Sox2 activation.