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Department of Cancer Biology (S.R.M., J.L.H., C.M.D., S.E.M., E.A.K., S.I.H., J.D.C., G.K.B., L.A.C.); Department of Cell and Developmental Biology (L.A.C.); Department of Medicine (L.A.C.), Division of Endocrinology, Diabetes and Metabolism, and Abramson Family Cancer Research Institute, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104-6160
Address all correspondence and requests for reprints to: Dr. Lewis Chodosh, Department of Cancer Biology, University of Pennsylvania School of Medicine, 612 Biomedical Research Building II/III, 421 Curie Boulevard, Philadelphia, Pennsylvania 19104-6160. E-mail: chodosh{at}mail.med.upenn.edu.
ABSTRACT
The use of DNA microarrays to study vertebrate organogenesis presents unique analytical challenges compared with expression profiling of homogeneous cell populations. We have used a general approach that permits the automated, unbiased identification of biologically relevant patterns of gene expression to study murine mammary gland development. Our studies confirm the utility of this approach by demonstrating the ready identification of cellular processes and pathways of known functional importance in mammary development. Additionally, this approach permitted the identification of genetic pathways with unpredicted patterns of developmental regulation, including those involved in angiogenesis, extracellular matrix synthesis, and the β-oxidation of fatty acids. Surprisingly, our findings demonstrate that the coordinate regulation of genes involved in the β-oxidation of fatty acids reflects the presence of an abundant, yet previously unrecognized stromal compartment within the mammary gland that is composed of brown adipose tissue. Our data demonstrate that the amount of brown adipose tissue present in the mammary gland is developmentally regulated; that PPAR
, Ucp1, and genes involved in fatty acid oxidation are spatially and temporally coregulated during development; that the mammary gland plays a functional role in adaptive thermogenesis; and that the transcriptional control of this adaptive response to cold is itself developmentally regulated.
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