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Differential Expression of GATA-4 and GATA-6 in Fetal and Adult Mouse and Human Adrenal Tissue

Children’s Hospital (S.K., M.W.-O., M.H.), Program for Developmental and Reproductive Biology (S.K., M.H.), Biomedicum Helsinki, and Department of Pathology (J.L., R.V.), University of Helsinki, 00290 Helsinki, Finland; Departments of Pediatrics (N.N., D.B.W., M.H.) and Molecular Biology and Pharmacology (D.B.W.), Washington University, St. Louis, Missouri 63110; and Department of Pediatrics, Kuopio University Hospital (R.V.), 70210 Kuopio, Finland

Address all correspondence and requests for reprints to: Markku Heikinheimo, M.D., Ph.D., Program for Developmental and Reproductive Biology, Biomedicum Helsinki, P.O. Box 63 (Haartmaninkatu 8), 00014 University of Helsinki, Finland. E-mail: . markku.heikinheimo{at}helsinki.fi

Earlier work implicates transcription factors GATA-4 and GATA-6 in murine adrenal function. We have now studied their expression during mouse and human adrenal development in detail. GATA-4 and GATA-6 mRNAs and protein are readily detectable from embryonic d 14 and gestational wk 19 onwards in the mouse and human adrenal cortex, respectively. In the postnatal adrenal, GATA-4 expression is down-regulated, whereas GATA-6 mRNA and protein continue to be expressed. To clarify the significance of GATA-4 for early adrenocortical development, Gata4-/- ES cells were injected into eight-cell-stage embryos derived from ROSA26 mice, a transgenic line expressing ß-galactosidase in all cell types, including the adrenocortical cells. The resultant chimeric embryos were stained with X-gal to discriminate ES cell- and host-derived tissue. Gata4-/- cells contributed to adrenocortical cells in these chimeras, and these cells also expressed GATA-6. Taken together, our findings suggest that GATA-6 expression is needed throughout adrenal development from fetal to adult age. GATA-4, on the other hand, may serve a role in the fetal adrenal gene regulation, although it is not essential for early adrenocortical differentiation.

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