="supplementary-material"}).

Whole mount staining of mammary gland {#S16}
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Inguinal mammary glands (number 4) were dissected at the indicated times of development and spread on glass slides. After fixation in Carnoy's fixative for 4 h at room temperature, the tissues were hydrated and stained in carmine alum as described on <http://mammary.nih.gov>. Samples were then dehydrated, cleared in Histoclear, and photographed. Counting of terminal end buds (TEBs) was performed by defining counting areas first, drawing 1mmX1mm squares on whole mount pictures, and taking the average number of TEBs from 5 randomly picked areas.

Immunohistochemistry {#S17}
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Inguinal mammary glands (number 4) were dissected from both MMTV-LRP6 transgenic mice and WT littermate controls, fixed in 4% phosphate-buffered paraformadehyde overnight, transferred to 70% ethanol, embedded in paraffin, and sectioned at 5μm. After deparaffinization, rehydration and antigen retrieval by heating in antigen unmasking solution (Dako, Carpinteria, CA), tissue slices were blocked with serum using Vectastain ABC kit (Vector Laboratories, Burlingame, CA), incubated with primary anti-hLRP6 antibody (R&D, Indianapolis, IN) or Ki67 antibody (Abcam, Cambridge, CA) at 4°C overnight. After washing with PBS, the slices were incubated with biotinylated secondary antibody for 30 min at room temperature, and detected by Histostain Plus DAB kit (Zymed Laboratories, CA).

H & E staining {#S18}
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Inguinal mammary glands (number 4) were excised, fixed with paraformadehyde, and embedded in paraffin. Sections were cut at 5 μm, dewaxed, rehydrated, and stained with hematoxylin and eosin.

TUNEL staining {#S19}
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Paraffin sections at 5 μm of mammary glands from MMVT-LRP6 and WT littermate controls were depariffinized. TUNEL staining was performed with TUNEL Apoptosis Detection kit (Upstate) following manufacturer's instructions, and nuclei were counterstained with DAPI 5 μg/ml for 5 min