THE TISSUE DISTRIBUTION OF ACTIVIN BETA(A)-SUBUNIT AND BETA(B)-SUBUNIT AND FOLLISTATIN MESSENGER RIBONUCLEIC-ACIDS SUGGESTS MULTIPLE SITES OF ACTION FOR THE ACTIVIN-FOLLISTATIN SYSTEM DURING HUMAN-DEVELOPMENT

Activins have potent effects on early morphogenetic events during amph ibian embryogenesis but no evidence for their role during human develo pment other than their expression in steroidogenic tissues has been re ported. We previously showed the expression of the activin type II and IIB receptor mRNAs in several tissues of the mid-gestational human fe tus with highest expression levels in developing neural, muscular and exocrine glandular organs. We now report that the mRNA transcripts for activin beta(A)- and beta(B)-subunits and for the activin-binding pro tein follistatin are found co-expressed in several of these extragonad al tissues. Their mRNAs were detected by Northern analyses using speci fic single-stranded P-32-labeled cDNA probes. In the nervous system, b oth activin beta(A)- and beta(B)-subunit transcripts were expressed in the cerebrum and spinal cord. Follistatin was abundantly expressed in the spinal cord whereas weaker signals where observed in the cerebrum and cerebellum. In the muscular system, beta(A)-subunit was abundantl y expressed in the heart but to a lesser extent in the skeletal muscle while the opposite was observed for follistatin. Follistatin, and act ivin beta(A)- and beta(B)-subunit mRNAs were also detected in developi ng kidney, salivary gland, liver, and adrenal. The predominance of bet a(A)-subunit mRNAs in the bone marrow and beta(B)-subunit mRNAs in the salivary gland suggests specific roles for activin A and B, respectiv ely, in these tissues. No hybridization signal was detected for the in hibin alpha-subunit in non-steroidogenic tissues indicating that, in c ontrast to activins and follistatin, the effects of inhibins may be re stricted to the gonads and adrenals which are known to express high le vels of the alpha-subunit transcript. Taken together, our results sugg est that the activin-follistatin system regulates the development of s everal organ systems in the mid-gestational human fetus.