Extracellular signal transduction into cells through ligand-activated receptor tyrosine kinases, such as insulin-like growth factor-1 (IGF-1) receptor (IGF-1R) and insulin receptor (IR) is required for normal embryonic growth and development. The major mediators of IR and IGF-1R are adaptor proteins of the insulin receptor substrate family, the best characterized member of which is IRS-1. Insulin receptor substrate IRS-1 has been shown to influence cell and body size and to interfere with differentiation. We have isolated IRS-1 from Xenopus laevis embryos and analyzed for the first time its spatial and temporal expression pattern during embryogenesis. We found that Xenopus IRS-1 is expressed maternally and constantly during embryogenesis. It is predominantly found in neural tissue at different stages. Furthermore, knock down of IRS-1 in neural tissue by specific antisense morpholino oligonucleotides (MO) resulted in abnormal eye formation accompanied by reduction of the eye-specific marker genes Rx1 and Pax6 and a decreased cell proliferation. Developmental Dynamics 240:1705-1715,