Functional microarray analysis of mammary organogenesis reveals a developmental role in adaptive thermogenesis.
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 beta-oxidation of fatty acids. Surprisingly, our findings demonstrate that the coordinate regulation of genes involved in the beta-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 PPARalpha, 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.
Master
Stephen R
SR
Department of Cancer Biology and Abramson Family Cancer Research Institute, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104-6160, USA.
Hartman
Jennifer L
JL
D'Cruz
Celina M
CM
Moody
Susan E
SE
Keiper
Elizabeth A
EA
Ha
Seung I
SI
Cox
James D
JD
Belka
George K
GK
Chodosh
Lewis A
LA
D002001:Adipose Tissue, Brown / Q000378:metabolism; D000818:Animals; D001940:Breast / Q000254:growth & development* / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism; D005227:Fatty Acids / Q000378:metabolism; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D007473:Ion Channels; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D024101:Mitochondrial Proteins; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods*; D038081:Organogenesis; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism; D022722:Thermogenesis; D014157:Transcription Factors / Q000378:metabolism; D000071256:Uncoupling Protein 1
D002352:Carrier Proteins; D005227:Fatty Acids; D007473:Ion Channels; D008565:Membrane Proteins; D024101:Mitochondrial Proteins; D018160:Receptors, Cytoplasmic and Nuclear; D014157:Transcription Factors; C000604372:Ucp1 protein, mouse; D000071256:Uncoupling Protein 1