Ablation of Indian hedgehog in the murine uterus results in decreased cell cycle progression, aberrant epidermal growth factor signaling, and increased estrogen signaling.
Conditional ablation of Indian hedgehog (Ihh) in the murine uterus results in mice that are sterile because of defects in embryo implantation. We performed microarray analysis on these mice at the time point at which the Ihh target genes are induced by the administration of exogenous hormone to mimic Day 3.5 of pregnancy. This analysis identified 863 genes altered by the conditional ablation of Ihh. Of these, genes that regulated the cell cycle were overrepresented. In addition, genes involved in epidermal growth factor (EGF) and estrogen (E2) signaling were found to be deregulated upon Ihh ablation. Furthermore, upon conditional ablation of Ihh, 15-mo-old mice exhibited hallmarks of estrogenized uteri, such as cystically dilated glands and hyalinized stroma. Thus, Ihh regulates embryo implantation by having an impact on the cell cycle, EGF signaling, and E2 signaling.
Franco
Heather L
HL
Departments of Molecular and Cellular Biology and Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA.
Lee
Kevin Y
KY
Broaddus
Russell R
RR
White
Lisa D
LD
Lanske
Beate
B
Lydon
John P
JP
Jeong
Jae-Wook
JW
DeMayo
Francesco J
FJ
D000818:Animals; D002453:Cell Cycle / Q000187:drug effects / Q000235:genetics* / Q000502:physiology; D010064:Embryo Implantation / Q000235:genetics; D004815:Epidermal Growth Factor / Q000378:metabolism* / Q000494:pharmacology / Q000502:physiology; D004958:Estradiol / Q000378:metabolism* / Q000494:pharmacology / Q000502:physiology; D005260:Female; D017353:Gene Deletion; D005786:Gene Expression Regulation / Q000187:drug effects; D018816:Genes, cdc / Q000187:drug effects / Q000502:physiology; D053823:Hedgehog Proteins / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D051379:Mice; D008822:Mice, Transgenic; D008954:Models, Biological; D011247:Pregnancy; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D014599:Uterus / Q000187:drug effects / Q000378:metabolism / Q000502:physiology
D053823:Hedgehog Proteins; C514061:ihh protein, mouse; D004958:Estradiol; D004815:Epidermal Growth Factor