HEAT SHOCK-INDUCED HOMEOTIC TRANSFORMATIONS OF THE AXIAL SKELETON ANDASSOCIATED SHIFTS OF HOX GENE-EXPRESSION DOMAINS IN MOUSE EMBRYOS

Pregnant ICR mice were immersed in water at 42 degrees C for up to 15 min on Day 8.5 of gestation (plug day Day 0), and their term fetuses w ere double stained with alcian blue and alizarin red S for skeletal ex amination. Heat exposure for 15 min induced homeotic vertebral transfo rmations in more than one-third of the living fetuses, in which the mo rphologic identity of vertebrae (T6-S1) was shifted anteriorly by one or two segmental levels. The frequency of fetuses with vertebral trans formations and the degree of the shift of vertebral identity were depe ndent on the length of heat exposure. The expression domains of Hoxa-7 , Hoxc-8, and Hoxc-9 genes as examined by whole mount in situ hybridiz ation were found to be shifted anteriorly in heated embryos, The heat- induced shifts of Hox gene expression domains were consistent with the observed vertebral transformations and suggested correlation or colin earity with the clustered organization of the Hox genes. The result of the present study indicates that a brief heat shock at a critical sta ge of differentiation can interfere with the normal establishment of H ox codes and subsequently, perturb the specification of vertebral iden tity. (C) 1997 Elsevier Science Inc.