γ-Secretase Functions through Notch Signaling to Maintain Skin Appendages but Is Not Required for Their Patterning or Initial Morphogenesis

The role of Notch signaling during skin development was analyzed using Msx2-Cre to create mosaic loss-of-function alleles with precise temporal and spatial resolution. We find that γ-secretase is not involved in skin patterning or cell fate acquisition within the hair follicle. In its absence, howev...

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Bibliographic Details
Published in:Developmental cell 2004-11, Vol.7 (5), p.731-743
Main Authors: Pan, Yonghua, Lin, Meei-Hua, Tian, Xiaolin, Cheng, Hui-Teng, Gridley, Thomas, Shen, Jie, Kopan, Raphael
Format: Article
Language:English
Subjects:
Amyloid Precursor Protein Secretases
Animals
Aspartic Acid Endopeptidases
Body Patterning - genetics
Cell Differentiation
Cell Lineage
Endopeptidases - metabolism
Epidermal Cyst - pathology
Gene Deletion
Gene Expression Regulation, Developmental
Gene Targeting
Hair Follicle - anatomy & histology
Hair Follicle - growth & development
Hair Follicle - ultrastructure
Immunohistochemistry
In Situ Hybridization
Membrane Proteins - genetics
Membrane Proteins - metabolism
Mice
Mice, Knockout
Models, Biological
Morphogenesis
Receptors, Notch
Sebaceous Glands - abnormalities
Skin - anatomy & histology
Skin - growth & development
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Summary:The role of Notch signaling during skin development was analyzed using Msx2-Cre to create mosaic loss-of-function alleles with precise temporal and spatial resolution. We find that γ-secretase is not involved in skin patterning or cell fate acquisition within the hair follicle. In its absence, however, inner root sheath cells fail to maintain their fates and by the end of the first growth phase, the epidermal differentiation program is activated in outer root sheath cells. This results in complete conversion of hair follicles to epidermal cysts that bears a striking resemblance to Nevus Comedonicus. Sebaceous glands also fail to form in γ-secretase-deficient mice. Importantly, mice with compound loss of Notch genes in their skin phenocopy loss of γ-secretase in all three lineages, demonstrating that Notch proteolysis accounts for the major signaling function of this enzyme in this organ and that both autonomous and nonautonomous Notch-dependent signals are involved.
ISSN:1534-5807
1878-1551
DOI:10.1016/j.devcel.2004.09.014