MESSENGER-RNA EXPRESSION PATTERNS OF THE IGF SYSTEM DURING MOUSE LIMBBUD DEVELOPMENT, DETERMINED BY WHOLE-MOUNT IN-SITU HYBRIDIZATION

During limb development the primary limb bud requires various signals to differentiate. Insulin-like growth factor (IGF)-I and IGF-II serve as ubiquitous cellular growth promoters and are modulated by their bin ding proteins (IGFBPs), which inhibit or augment IGF bioavailability. This is the first study to give a complete overview of the mRNA expres sion patterns of Igf-l, Igf-2, type 1 Igf-receptor (Igf1r) and six Igf binding proteins (IGFBP-1-6) in embryonic mouse limbs, at various sta ges of development, by whole mount in situ hybridization (ISH). Our re sults show that all the members of the Igf system, except Igfbp-1 and -6, have specific spatio-temporal mRNA expression patterns. IGFBP-2 an d -5 are found in the apical ectodermal ridge (AER), and IGF-I and IGF BP-4 in the region of the zone of polarizing activity (ZPA). IGF-II an d IGF1R are found in regions of pre-cartilage formation. At 13.5 days post coitus (dpc) the IGF system colocalizes with apoptosis areas; IGF BP-2, -4 and -5 are found in the interdigital zone, while IGFBP-3 and IGF-I border this region. Furthermore, IGFBP-3, -4 and -5 are found in the phalangeal joint areas, at an early stage of joint formation. Thi s supports the hypothesis that the IGF system may be involved in chond rogenic differentiation of mesenchyme and the regulation of apoptosis in the developing limb. (C) 1998 Elsevier Science Ireland Ltd. All rig hts reserved.