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Hedgehog Signaling Pathway

Hedgehog Signaling Pathway

The Hedgehog gene (Hh) was first discovered due to its control of the growth of disorganized, hair-like bristles phenotype in Drosophila, much like hedgehog spines. Hh plays a crucial role in the development of organs and the maintenance of homeostasis in both invertebrates and vertebrates. However, while Drosophila has only one Hh protein, mammals have multiple functional Hedgehog proteins - Sonic (Shh), Desert (Dhh), and Indian Hedgehog (Ihh). All of these homologous proteins have adapted to...

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Cell Population Analyses During Skin Carcinogenesis

Cell Population Analyses During Skin Carcinogenesis

Published on: August 21, 2013

Epidermal hyperplasia and appendage abnormalities in mice lacking CD109.

Shinji Mii¹, Yoshiki Murakumo, Naoya Asai

¹Department of Pathology, Nagoya University Graduate School of Medicine, Nagoya, Japan.

The American Journal of Pathology

|August 1, 2012

Summary

CD109 deficiency in mice impairs hair growth and alters epidermal structure. This suggests CD109 regulates keratinocyte differentiation through the Stat3 signaling pathway in vivo.

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Area of Science:

Cell Biology
Dermatology
Molecular Biology

Background:

CD109 is a glycoprotein highly expressed in squamous cell carcinomas and certain normal tissues.
Its physiological role in vivo, particularly in skin, is largely unknown.
Previous in vitro studies suggested CD109 negatively regulates TGF-β signaling.

Purpose of the Study:

To investigate the in vivo function of CD109.
To elucidate the role of CD109 in skin homeostasis and keratinocyte differentiation.

Main Methods:

Generation of CD109-deficient (CD109(-/-)) mice.
Histological and immunohistochemical analysis of skin and hair follicles.
Analysis of signaling pathways, including Smad2 phosphorylation and Stat3 phosphorylation.

Main Results:

CD109(-/-) mice exhibited transient hair growth impairment, kinked hair, and epidermal hyperplasia.
Histology showed thickened epidermal layers and sebaceous gland hyperplasia in CD109(-/-) mice.
Elevated Stat3 phosphorylation, but not Smad2 phosphorylation, was observed in the epidermis of CD109(-/-) mice.

Conclusions:

CD109 plays a role in regulating hair growth and skin homeostasis.
CD109 appears to regulate keratinocyte differentiation.
The Stat3 signaling pathway is implicated in CD109's function in the epidermis.