Posted on: January 30, 2002
"I remember Nov. of 2001, when Dr. Elaine Fuchs from University of Chicago, gave a talk in UCLA. She was talking about her work, about her cutest mutant mouse - "chubby mouse". This mouse over-expressed stabilized beta-catenin, which resulted in constant new hair formation. She told, that next they published their work, they got literary 100 calls per day. Balding people were asking for a the cost a vial of beta-catenin...OK. So, here is the continuation of this story."
Clonemyhair Admin
Since, Dr. Fuchs' lab showed, that over-expression of stable form of beta-catenin results in de novo hair follicle formation and, by the way, cause hair-type specific tumors, now attempt to create opposite mutant was done. Successful.
Background: Protein Lef1 interact with beta-catening in cells' nuclei, causing activation of beta-cat/Lef1 dependent transcription activation. This pathway is crucial in hair biology.
Now, modified Lef1 cDNA was created (DeltaNLef1), that lacked the part, interaction with beta-cat. This Lef1 construct was specifically expressed in epidermis. This abnormal Lef1 presence inhibited normal beta-cat/lef1 pathway, thus leading to almost opposite result as beta-cat constitutive activation in Dr. Fuchs work. After, first normal hair cycle, mice developed progressive hair abnormalities: hair follicle loss, associated with the formation of cysts. I.e., under the influence of abnormal Lef1, hair follicle epithelial cells (stem cells or their direct progenitors) stopped to develop in proper (hair-like) way. Instead, they switched they program to epidermal one!
Also, this mutant mouse developed skin tumors. Yet, those tumors were different from beta-cat induced. Instead of hair-type tumors, epidermal- and sebaceous-type of tumors were formed.
Thus, "based on our results and previous data on the consequences of activating beta-catenin/Lef1 signaling in postnatal keratinocytes, we conclude that the level of beta-catenin signaling determines whether keratinocytes differentiate into hair or interfollicular epidermis, and that perturbation of the pathway by over-expression of DeltaNLef1 can lead to skin tumor formation" author conclude.
Based on: "Expression of DeltaNLef1 in mouse epidermis results in differentiation of hair follicles into squamous epidermal cysts and formation of skin tumours."
From: Development 2002 Jan;129(1):95-109
By: Niemann C, Owens DM, Hulsken J, Birchmeier W, Watt FM. |
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