Journal
DEVELOPMENTAL DYNAMICS
Volume 235, Issue 12, Pages 3404-3412Publisher
WILEY-LISS
DOI: 10.1002/dvdy.20978
Keywords
branching morphogenesis; mammary gland; microarray profiling; terminal end buds; wnt signaling; hedgehog signaling
Categories
Funding
- NCI NIH HHS [R01 CA057621-13S1, CA057621, R01 CA057621, R01 CA057621-14, R01 CA057621-13] Funding Source: Medline
- NIEHS NIH HHS [ES012801, U01 ES012801, U01 ES012801-04S3] Funding Source: Medline
Ask authors/readers for more resources
The mammary gland develops in a process known as branching morphogenesis, whereby a distal epithelial bud extends and bifurcates to form an extensive ductal network. Compared with other branched organs, such as the lung and kidney, little is known about the molecular basis of branching in the mammary gland. Here we report a microarray profiling strategy to identify novel genes that may regulate mammary branching. We microdissected terminal end bud (TEB) and mature duct microenvironments from P-actin-green fluorescent protein reporter mice and compared their RNA expression profiles with epithelium-free mammary stroma by means of microarray. We identified 1,074 genes enriched in the TEB microenvironment, 222 genes enriched in the mature duct microenvironment, and 385 genes enriched in both TEB and mature duct microenvironments. The microarray correctly predicted the expression of genes known to be enriched in the epithelium (Ets-5) and stroma (MMP-14) of TEBs and in the mature duct microenvironment (MMP-3). The microarray also correctly predicted the localization of previously uncharacterized genes, such as the TEB-enriched SPRR-1a, the duct-enriched casein-gamma, and the general epithelial marker pleiotrophin. Analysis of genes enriched in TEBs revealed several genes in the Wnt (Wnt-2, Wnt-5a, Wnt-7b, Dsh-3, Frizzled-1, Frizzled-2), hedgehog (Dhh), ephrin (Ephrin-B1, Eph-A2), and transcription factor (Twist-1, Twist-2, Snail) families. In situ hybridization verified that these genes were enriched in the TEB epithelium (Wnt-5a, Wnt-7b, Dhh, Eph-A2) or TEB stroma (Wnt-2, Frizzled-1, Ephrin-B1). We discuss the potential roles of these genes in mammary branching morphogenesis.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available