mRNA and protein localization of the IGF system during mouse embryonic development in areas with apoptosis.
We analysed mRNA and protein localization of the IGF system components in regions with apoptosis during mouse development between 9.5 and 13.5 days post coitum. A spatio-temporal relationship between these expression patterns and the onset of apoptosis in specific areas was sought. The IGFBP mRNA and protein expression patterns were tissue-specific. In most tissues, mRNA expression patterns colocalized with protein localization. Discrepancies between mRNA and protein detection were found in, for example, lens, neural layer of the retina, whiskers and somites. Localization of the IGFs, the type I IGF receptor and IGFBP-2 correlated well with cell death regions. When these genes were expressed no apoptosis occurred and vice versa. Correlation of IGFBP-3, -4 and -5 with apoptosis regions was noticed only at 13.5 days post coitum. In eye muscles, whiskers and somites, the expression of IGF system components preceded the occurrence of apoptotic cells. When IGF-I expression ceased, apoptosis occurred in these areas. In conclusion, our results suggest that IGF-I, the type I IGF receptor and IGFBP-2 inhibit apoptosis. In contrast, IGFBP-3, -4 and -5 may stimulate apoptosis by trapping the IGFs. Tissue-specific modulation of IGF protective action against apoptosis by the different IGFBPs during mouse embryonal development may contribute to organ specific morphology.
Kleffens
M
M
Laboratory of Pediatrics, Subdivision of Molecular Endocrinology, Erasmus University, Dr. Molewaterplein 50, Rotterdam, 3015 GD, Netherlands.
Groffen
C
C
Neck
J W
JW
Vermeij-Keers
C
C
Drop
S L
SL
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D004622:Embryo, Mammalian / Q000033:anatomy & histology; D005121:Extremities / Q000196:embryology; D005456:Fluorescent Dyes / Q000494:pharmacology; D018507:Gene Expression Regulation, Developmental; D006257:Head / Q000196:embryology; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D020287:In Situ Nick-End Labeling; D018969:Insulin-Like Growth Factor Binding Proteins / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D009333:Neck / Q000196:embryology; D010078:Oxazines / Q000494:pharmacology; D011506:Proteins / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis*; D013002:Somatomedins / Q000235:genetics* / Q000378:metabolism*; D013997:Time Factors
D005456:Fluorescent Dyes; D018969:Insulin-Like Growth Factor Binding Proteins; D010078:Oxazines; D011506:Proteins; D012333:RNA, Messenger; D013002:Somatomedins; C008619:Nile Blue