Neuregulin induces the expression of mesodermal genes in the ectoderm of Xenopus laevis

The primary patterning event in early vertebrate development is the formati on of mesoderm and subsequent induction of the neural tube by the mesoderm, Some of the transforming growth factor (TGF)-beta family (Activin, Vg1) an d the fibroblast growth factor (FGF) family molecules have been implicated for their roles in mesoderm induction. Here we show first the evidence that neuregulin, an epidermal growth factor (EGF) - like growth factor known fo r its role in neural and muscle differentiation, participates in mesoderm i nduction. Neuregulin could induce the ectopic expression of mesoderm specif ic gene Xbra in animal cap explants reared to the midgastrula stage, when a nimal caps dissected from late blastula were cultured with Neuregulin at a low concentration (10 ng/ml), In situ hybridization study showed that alpha -cardiac actin was expressed in animal caps that were treated with Neuregul in overnight, Skeletal and cardiac muscle specific genes such as MyoD famil y genes (myoD, MRF4, myf5) and SL1 as well as NCAM, a pan neural marker, we re also ectopically expressed by treatment with Neuregulin, However, the ex pression of NCAM is presumed to be a secondary result of the initial mesode rm induction by Neuregulin, The temporal expression pattern of neuregulin d uring the early developmental stages was analyzed by RT-PCR in order to det ermine if neuregulin is expressed at the time of mesoderm induction. It has been found that the neuregulin transcript was already detected from the 16 -cell stage (stage 5) and continued to be expressed till the tailbud stage (stage 25), the latest embryonic stage analyzed in this study. Considering that the mesoderm is induced at early blastula before the start of zygotic transcription, maternal neuregulin is expressed at the right time to partic ipate in mesoderm induction. These data strongly suggest that neuregulin pl ays an important role in mesoderm induction.