Abnormal hair development and apparent follicular transformation to mammary gland in the absence of Hedgehog signaling

• Here, we show that removing the Shh receptor Smoothened from the skin epithelium results in a seemingly contradictory constellation of phenotypes including cellular disorganization, altered proliferation, and loss of hair follicle (HF) progenitors. We provide evidence that the lack of Smoothened in the epithelium results in excess Shh levels in the mesenchyme. Thus, the observed defects can be attributed not only to decreased epithelial Shh signaling, but increased mesenchymal Shh signalling. The latter contributes to exuberant HF induction, while the former depletes the resulting follicular stem cell niches. Two additional, unanticipated epithelial requirements for Shh relate to the robust acquisition of appropriate cell type identities: In the mutant mice, follicular outer root sheath takes on an epidermal character, and certain HF disappear altogether, having adopted a strikingly mammary gland-like fate. Our study uncovers a multifaceted function for Shh in sculpting and maintaining the integrity and identity of the developing HF.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Odontologi (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Dentistry (hsv//eng)

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)

NATURVETENSKAP  -- Biologi -- Utvecklingsbiologi (hsv//swe)

NATURAL SCIENCES  -- Biological Sciences -- Developmental Biology (hsv//eng)

Nyckelord

Sonic hedgehog

Smoothened

cell signaling

epithelium

mesenchyme

stem cell

Publikations- och innehållstyp

ref (ämneskategori)

art (ämneskategori)