Abstract
Like other skin appendages, the embryonic mammary gland develops via extensive epithelial–mesenchymal interactions. Early stages in embryonic mammary development strikingly resemble analogous steps in the development of hair follicles and teeth. In each case the first morphological sign of development is a localized thickening in the surface epithelium that subsequently invaginates to form a mammary, hair follicle or tooth bud. Similar sets of intersecting signaling pathways are involved in patterning the mammary, hair follicle and dental epithelium, directing placode formation, and controlling bud invagination. Despite these similarities, subsequent events in the formation of these appendages are diverse. The mammary bud extends to form a sprout that begins to branch upon contact with the mammary fat pad. Hair follicles also extend into the underlying mesenchyme, but instead of branching, hair follicle epithelium folds around a condensation of dermal cells. In contrast, teeth undergo a more complex folding morphogenesis. Here, we review what is known of the molecular and cellular mechanisms controlling early steps in the development of these organs, attempt to unravel both common themes and unique aspects that can begin to explain the diversity of appendage formation, and discuss human genetic diseases that affect appendage morphogenesis.
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Abbreviations
- ADULT:
-
acro-dermato-ungual-lacrimal-tooth syndrome
- APC:
-
adenomatous Polyposis Coli
- AREG:
-
Amphiregulin
- AEC:
-
ankyloblepharon-ectodermal dysplasia-clefting syndrome
- BCC:
-
basal cell carcinoma
- BMP:
-
bone morphogenetic protein
- DKK1:
-
Dickkopf 1
- EDA:
-
Ectodysplasin
- EDAR:
-
edctodysplasin receptor
- EEC:
-
ectrodactyly-ectodermal-dysplasia-clefting syndrome
- E:
-
embryonic day
- FGFR:
-
fibroblast growth factor receptor
- LMS:
-
limb-mammary syndrome
- NRG3:
-
Neuregulin 3
- SHFM:
-
non-syndromic split-hand/split-foot malformation
- PTHrP:
-
parathyroid hormone-related protein
- SEM:
-
scanning electron microscopy
- SHH:
-
Sonic hedgehog
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Acknowledgements
Research in Sarah Millar’s laboratory is supported by NIH grants R01-AR47709 and R01- DE015342.
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Mikkola, M.L., Millar, S.E. The Mammary Bud as a Skin Appendage: Unique and Shared Aspects of Development. J Mammary Gland Biol Neoplasia 11, 187–203 (2006). https://doi.org/10.1007/s10911-006-9029-x
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DOI: https://doi.org/10.1007/s10911-006-9029-x