Stage-specific homeotic vertebral transformations in mouse fetuses induced by maternal hyperthermia during somitogenesis.

To investigate the heat shock effects upon somitogenesis and specification of the vertebral identity, pregnant ICR mice were briefly exposed to 42 degrees C or 43 degrees C at E7.5, E8.5, or E9.5 (noon of the plug day = E0.5). Heat treatment induced embryonic day-specific vertebral transformations whose frequency and severity were dependent on the temperature elevation. Following a heat treatment at E8.5, the vertebral identity of T6 through S1 was shifted anteriorly by one or two segments (posterior transformations). Such shifts were found in more than one-third of the fetuses heat-stressed at 42 degrees C, and in over 90% of those exposed to 43 degrees C. When heated at E7.5, the anterior boundary of vertebral transformations was shifted cranially to cervical levels (C1-C7), and when heated at E9.5, it was shifted caudally to the lower thoracic and lumbar levels (T13-L4). Examination of Hox gene expression domains by in situ hybridization showed that the anterior boundaries of Hoxa-5, Hoxa-7, Hoxc-8, and Hoxc-9 expression domains in the paraxial mesoderm were shifted cranially by one somite segment in embryos heated at E7.5, as compared with the corresponding levels of their expression in control embryos. Such cranial shifts were found for Hoxa-7, Hoxc-8 and Hoxc-9, but not for Hoxa-5, in embryos heated at E8.0. In embryos heated at E8.5, only the expression domains for Hoxc-8 and Hoxc-9 were found to be shifted. The observed stage-specific vertebral transformations and shifts of the Hox gene expression domains were consistent with the temporal colinearity and posterior predominance of Hox gene expression during development. Further histological and cytochemical analyses revealed that heat-induced vertebral transformations may not be a result of induced cell death, but heat-induced transient arrest of cell proliferation and somitogenesis could result in altered expression of Hox genes and subsequently produce vertebral transformations.