The role of exogenous growth-promoting factors and their receptors in embryogenesis.
During organogenesis, the cells of the embryo may require growth factors that promote a cascade of intracellular events. An absolute requirement for exogenous insulin by presomite 9.5-d rat embryos grown in culture has been demonstrated. The uptake and processing of insulin and insulin-like growth factor-I showed different uptake and localization patterns. When epidermal growth factor (EGF) or "long EGF" is added to media depleted of low molecular weight material, a dose-dependent improvement in growth is observed. Furthermore, the specific EGF receptor signal transduction inhibitor Tyrphostin 47 can inhibit embryonic growth when it is administered in culture. When Tyrphostin 47 was microinjected into embryos on Day 11 and their growth and differentiation evaluated on Day 12 of gestation, a dose-dependent decrease in developmental score was observed. Thus, exogenous growth factors may be essential to normal rat development and these may be synthesized locally in the decidua or placental tissues. Perturbations to ligand-receptor interactions may be a mechanism for dysmorphogenesis.
Pratten
M K
MK
Department of Human Anatomy and Cell Biology, The Medical School, Queens Medical Centre, Nottingham, United Kingdom. Margaret.Pratten@nottingham.ac.uk
D000818:Animals; D046508:Culture Techniques; D004305:Dose-Response Relationship, Drug; D004622:Embryo, Mammalian / Q000187:drug effects / Q000502:physiology*; D005314:Embryonic and Fetal Development / Q000187:drug effects / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004815:Epidermal Growth Factor / Q000494:pharmacology / Q000502:physiology*; D005260:Female; D007328:Insulin / Q000494:pharmacology / Q000502:physiology*; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology / Q000502:physiology*; D009570:Nitriles / Q000494:pharmacology; D011247:Pregnancy; D051381:Rats; D017208:Rats, Wistar; D017978:Receptors, Growth Factor / Q000502:physiology*; D020032:Tyrphostins; D015017:Yolk Sac / Q000187:drug effects
D004791:Enzyme Inhibitors; D007328:Insulin; D009570:Nitriles; D017978:Receptors, Growth Factor; D020032:Tyrphostins; C060152:tyrphostin 47; D004815:Epidermal Growth Factor; D007334:Insulin-Like Growth Factor I