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  1. #11
    Senior Member
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    May 2014
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    BUMP.


    The Sonic Hedgehog signalling pathway sparked my interest again after reading this study; http://www.ncbi.nlm.nih.gov/pubmed/23211596

    Cell cycle re-entry by cochlear supporting cells and/or hair cells is considered one of the best approaches for restoring hearing loss as a result of hair cell damage. To identify mechanisms that can be modulated to initiate cell cycle re-entry and hair cell regeneration, we studied the effect of activating the sonic hedgehog (Shh) pathway. We show that Shh signaling in postnatal rat cochleae damaged by neomycin leads to renewed proliferation of supporting cells and hair cells.
    I share the frustration though of OP, it's a problem. I'm not saying SHH is the answer but it is possible that a (most likely unexplored in vivo humans) pathway can reverse miniaturization. However a very important question rises then if that particular pathway will be safe to modulate. Even if potential arises, some will just never hit the clinical setting because of this reason.

    As you can read however it seems that SHH has a rather prominent role in hair follicle biology. For example inhibition of Hedgehog signalling by vismodegib induces alopecia in more than 65% of the subjects which can even be persistent;



    In the following review they talk about the Hedgehog signalling pathway, regeneration and specific tissues like bone, skin, teeth ;

    http://dev.biologists.org/content/141/18/3445

    Growing evidence indicates that HH regulates diverse quiescent stem cell populations, but the exact roles that HH signaling plays in adult organ homeostasis and regeneration remain poorly understood. Here, we review recently identified functions of HH in modulating the behavior of tissue-specific adult stem and progenitor cells during homeostasis, regeneration and disease. We conclude that HH signaling is a key factor in the regulation of adult tissue homeostasis and repair, acting via multiple different routes to regulate distinct cellular outcomes, including maintenance of plasticity, in a context-dependent manner.
    The morphogen Sonic hedgehog (Shh) controls the growth of multipotent progenitor cells in many tissues, including limb, bone, and skin (Callahan and Oro, 2001; Ingham and McMahon, 2001; Taipale and Beachy, 2001).
    Last edited by Winston; 12-16-2015 at 01:28 PM. Reason: Please refer to our posting policies and TOS.

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