Loss of steroidogenic factor 1 alters cellular topography in the mouse ventromedial nucleus of the hypothalamus.
Knockout (KO) mice lacking the orphan nuclear receptor steroidogenic factor 1 (SF-1) exhibit marked structural abnormalities of the ventromedial nucleus of the hypothalamus (VMH). In this study, we sought to determine the molecular mechanisms underlying the VMH abnormalities. To trace SF-1-expressing neurons, we used a SF-1/enhanced green fluorescent protein (eGFP) transgene. Although the total numbers of eGFP-positive cells in wild-type (WT) and SF-1 KO mice were indistinguishable, cells that normally localize precisely within the VMH were scattered more diffusely in adjacent regions in SF-1 KO mice. This abnormal distribution is likely due to the loss of SF-1 expression in VMH neurons rather than secondary effects of deficient steroidogenesis, as redistribution also was seen in mice with a CNS-specific KO of SF-1. Thus, the absence of SF-1 alters the distribution of cells that normally form the VMH within the mediobasal hypothalamus. Consistent with this model, the hypothalamic expression patterns of the transcription factors islet-1 and nkx2.1 also were displaced in SF-1 KO mice. Independent of gene expression, birthdate analyses further suggested that cells with earlier birthdates were affected more severely by the loss of SF-1 than were later born cells. We conclude that the absence of SF-1 causes major changes in cellular arrangement within and around the developing VMH that result from altered cell migration.
Davis
Aline M
AM
Framingham State College, Framingham, Massachusetts 01701, USA.
Seney
Marianne L
ML
Stallings
Nancy R
NR
Zhao
Liping
L
Parker
Keith L
KL
Tobet
Stuart A
SA
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism; D000818:Animals; D019521:Body Patterning / Q000235:genetics; D002454:Cell Differentiation / Q000235:genetics; D002455:Cell Division / Q000235:genetics; D002465:Cell Movement / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000172:deficiency* / Q000235:genetics; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000235:genetics*; D012739:Gonadal Steroid Hormones / Q000096:biosynthesis; D018398:Homeodomain Proteins; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009421:Nervous System Malformations / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D009474:Neurons / Q000378:metabolism / Q000473:pathology*; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism; D054339:Steroidogenic Factor 1; D000074482:Thyroid Nuclear Factor 1; D014157:Transcription Factors / Q000096:biosynthesis / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D019076:Transgenes / Q000235:genetics; D014697:Ventromedial Hypothalamic Nucleus / Q000002:abnormalities* / Q000378:metabolism / Q000473:pathology
D048868:Adaptor Proteins, Signal Transducing; D004268:DNA-Binding Proteins; D012739:Gonadal Steroid Hormones; D018398:Homeodomain Proteins; C490665:Mapk8ip protein, mouse; C000614414:Nkx2-1 protein, mouse; D009687:Nuclear Proteins; D018160:Receptors, Cytoplasmic and Nuclear; D011993:Recombinant Fusion Proteins; D054339:Steroidogenic Factor 1; D000074482:Thyroid Nuclear Factor 1; D014157:Transcription Factors; C515058:steroidogenic factor 1, mouse