The Gli2 Transcription Factor Is Required for Normal Mouse Mammary Gland Development

Autor: Phyllis Strickland, Charles W. Daniel, Michael T. Lewis, Sarajane Ross, Elsa Jimenez, Chi-chung Hui, Charles W. Sugnet
Rok vydání: 2001
Předmět:
Time Factors
Epithelium
Mice
0302 clinical medicine
Pregnancy
In Situ Hybridization
0303 health sciences
Mice
Inbred BALB C
Homozygote
Gene Expression Regulation
Developmental
Zinc Fingers
Cell biology
medicine.anatomical_structure
Phenotype
030220 oncology & carcinogenesis
Female
Signal Transduction
medicine.medical_specialty
Heterozygote
Stromal cell
animal structures
Genotype
Kruppel-Like Transcription Factors
Mice
Nude
Mammary Neoplasms
Animal
Biology
Zinc Finger Protein Gli2
03 medical and health sciences
Mammary Glands
Animal
GLI1
GLI2
Internal medicine
GLI3
medicine
Animals
Hedgehog Proteins
RNA
Messenger
Hedgehog
Molecular Biology
Alleles
030304 developmental biology
Transplantation
Wild type
Epithelial Cells
Cell Biology
Endocrinology
biology.protein
Trans-Activators
Transcription Factors
Developmental Biology
Zdroj: Developmental Biology, vol 238, iss 1
ISSN: 0012-1606
DOI: 10.1006/dbio.2001.0410
Popis: The hedgehog signal transduction network performs critical roles in mediating cell-cell interactions during embryogenesis and organogenesis. Loss-of-function or misexpression mutation of hedgehog network components can cause birth defects, skin cancer, and other tumors. The Gli gene family (Gli1, Gli2, and Gli3) encodes zinc finger transcription factors that act as mediators of hedgehog signal transduction. In this study, we investigate the role of Gli2 in mammary gland development. Mammary expression of Gli2 is developmentally regulated in a tissue compartment-specific manner. Expression is exclusively stromal during virgin stages of development but becomes both epithelial and stromal during pregnancy and lactation. The null phenotype with respect to both ductal and alveolar development was examined by transplantation rescue of embryonic mammary glands into physiologically normal host females. Glands derived from both wild type and null embryo donors showed ductal outgrowths that developed to equivalent extents in virgin hosts. However, in null transplants, ducts were frequently distended or irregularly shaped and showed a range of histological alterations similar to micropapillary ductal hyperplasias in the human breast. Alveolar development during pregnancy was not overtly affected by loss of Gli2 function. Ductal defects were not observed when homozygous null epithelium was transplanted into a wild type stromal background, indicating that Gli2 function is required primarily in the stroma for proper ductal development. DeltaGli2 heterozygotes also demonstrated an elevated frequency and severity of focal ductal dysplasia relative to that of wild type littermate- and age-matched control animals.
Databáze: OpenAIRE
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