Adrenal Development in Mice Requires GATA4 and GATA6 Transcription Factors.
The adrenal glands consist of an outer cortex and an inner medulla, and their primary purposes include hormone synthesis and secretion. The adrenal cortex produces a complex array of steroid hormones, whereas the medulla is part of the sympathetic nervous system and produces the catecholamines epinephrine and norepinephrine. In the mouse, GATA binding protein (GATA) 4 and GATA6 transcription factors are coexpressed in several embryonic tissues, including the adrenal cortex. To explore the roles of GATA4 and GATA6 in mouse adrenal development, we conditionally deleted these genes in adrenocortical cells using the Sf1Cre strain of animals. We report here that mice with Sf1Cre-mediated double deletion of Gata4 and Gata6 genes lack identifiable adrenal glands, steroidogenic factor 1-positive cortical cells and steroidogenic gene expression in the adrenal location. The inactivation of the Gata6 gene alone (Sf1Cre;Gata6(flox/flox)) drastically reduced the adrenal size and corticosterone production in the adult animals. Adrenocortical aplasia is expected to result in the demise of the animal within 2 weeks after birth unless glucocorticoids are provided. In accordance, Sf1Cre;Gata4(flox/flox)Gata6(flox/flox) females depend on steroid supplementation to survive after weaning. Surprisingly, Sf1Cre;Gata4(flox/flox)Gata6(flox/flox) males appear to live normal lifespans as vital steroidogenic synthesis shifts to their testes. Our results reveal a requirement for GATA factors in adrenal development and provide a novel tool to characterize the transcriptional network controlling adrenocortical cell fates.
Department of Physiological Sciences (S.G.T., E.J., H.M.H., T.J., S.C.F., M.B.P.), College of Veterinary Medicine, University of Florida, Gainesville, Florida 32610-0144; and Department of Applied Physiology and Kinesiology (D.A.M.), College of Health and Human Performance, University of Florida, Gainesville, Florida 32611-8200.
Sergei G
SG
Tevosian
Department of Physiological Sciences (S.G.T., E.J., H.M.H., T.J., S.C.F., M.B.P.), College of Veterinary Medicine, University of Florida, Gainesville, Florida 32610-0144; and Department of Applied Physiology and Kinesiology (D.A.M.), College of Health and Human Performance, University of Florida, Gainesville, Florida 32611-8200.
Elizabeth
E
Jiménez
Department of Physiological Sciences (S.G.T., E.J., H.M.H., T.J., S.C.F., M.B.P.), College of Veterinary Medicine, University of Florida, Gainesville, Florida 32610-0144; and Department of Applied Physiology and Kinesiology (D.A.M.), College of Health and Human Performance, University of Florida, Gainesville, Florida 32611-8200.
Heather M
HM
Hatch
Department of Physiological Sciences (S.G.T., E.J., H.M.H., T.J., S.C.F., M.B.P.), College of Veterinary Medicine, University of Florida, Gainesville, Florida 32610-0144; and Department of Applied Physiology and Kinesiology (D.A.M.), College of Health and Human Performance, University of Florida, Gainesville, Florida 32611-8200.
Tianyu
T
Jiang
Department of Physiological Sciences (S.G.T., E.J., H.M.H., T.J., S.C.F., M.B.P.), College of Veterinary Medicine, University of Florida, Gainesville, Florida 32610-0144; and Department of Applied Physiology and Kinesiology (D.A.M.), College of Health and Human Performance, University of Florida, Gainesville, Florida 32611-8200.
Deborah A
DA
Morse
Department of Physiological Sciences (S.G.T., E.J., H.M.H., T.J., S.C.F., M.B.P.), College of Veterinary Medicine, University of Florida, Gainesville, Florida 32610-0144; and Department of Applied Physiology and Kinesiology (D.A.M.), College of Health and Human Performance, University of Florida, Gainesville, Florida 32611-8200.
Shawna C
SC
Fox
Department of Physiological Sciences (S.G.T., E.J., H.M.H., T.J., S.C.F., M.B.P.), College of Veterinary Medicine, University of Florida, Gainesville, Florida 32610-0144; and Department of Applied Physiology and Kinesiology (D.A.M.), College of Health and Human Performance, University of Florida, Gainesville, Florida 32611-8200.
Maria B
MB
Padua
D015096:3-Hydroxysteroid Dehydrogenases / Q000378:metabolism; D000302:Adrenal Cortex / Q000196:embryology / Q000378:metabolism; D000311:Adrenal Glands / Q000196:embryology* / Q000378:metabolism; D000309:Adrenal Insufficiency / Q000235:genetics*; D000818:Animals; D003345:Corticosterone / Q000378:metabolism; D005260:Female; D050991:GATA4 Transcription Factor / Q000235:genetics*; D050993:GATA6 Transcription Factor / Q000235:genetics*; D017353:Gene Deletion; D015870:Gene Expression; D000075262:Hypoadrenocorticism, Familial; D008297:Male; D051379:Mice; D012333:RNA, Messenger / Q000378:metabolism*; D012737:Sex Factors; D054339:Steroidogenic Factor 1 / Q000378:metabolism; D013737:Testis / Q000378:metabolism
D050991:GATA4 Transcription Factor; D050993:GATA6 Transcription Factor; C484171:Gata4 protein, mouse; C494760:Gata6 protein, mouse; D012333:RNA, Messenger; D054339:Steroidogenic Factor 1; C515058:steroidogenic factor 1, mouse; D015096:3-Hydroxysteroid Dehydrogenases; D003345:Corticosterone