.1. For the Benefit of Antler Biologists
Resistance of stem cells in the mouse HF bulge to DNA-damage-induced cell death is a consequence of higher expression of the antiapoptotic protein Bcl-2, enhanced DNA repair activity, and the rapidly attenuated activity of p53 [117]. Expression of Bcl-2 is also observed in the mesenchymal tissue of antler (transient amplifying cells [118]); is this gene also expressed in the AP and/or PP tissue? If it is, this gene may also be important for the maintenance of antler stem cells.
In HFs, telogen can be divided into a phase that is refractory to HF growth stimuli and that is characterized by upregulation and activation of BMP2/4 and a competent phase in which bulge stem cells become highly sensitive to anagen-inducing factors [119]. In the competent phase of regenerating HFs, BMP signalling is turned off while Wnt/b-catenin signalling is turned on to reach its optimal activity in early anagen. How about AUs? The transition from velvet to hard antler can also be divided into refractory and competent phases to mitogenic factors. Do the factors that operate in the HFs also function in AUs?
8.2. For the Benefit of HF Biologists
Formation of the pedicle is independent of the E-M interactions and is solely triggered by the increase in concentrations of circulating androgen hormones [15]. When the pedicle reaches the species-specific height, AP-derived mesenchymal tissue becomes closely associated with the overlying skin and the two tissue components are then able to interact and initiate growth of the antler [17]; that is, anything formed through the E-M interactions during the initial AU generation will be destroyed and rebuilt in subsequent cycles of antler growth. How does this compare with HFs? Morphologically, at the early stage (before development of the HF peg), no obvious aggregation of dermal cells can be detected under the HF placode [5]. The molecular nature of the earliest cues of HF-inducing signals from the dermis remains unclear [120]. Is it possible that the permanent part of the HF is also formed independently of E-M interactions? It is known that the formation of the epidermal placode from which the HF will be formed is specified by reaction-diffusion waves [121]. It is also well established that E-M interactions are indispensible for the formation of the temporary/cyclic component of HF in subsequent regeneration cycles. Therefore, it is tempting to postulate that the formation of the initial permanent component of the HFs is also independent of the E-M interactions.
Nascent velvet skin contains HFs [52], indicating that these are formed de novo. It would be interesting to know what chemical factors are involved in this induction. Interestingly, HFs that are formed in the velvet skin have much larger sebaceous glands, but there are no arrector pili muscles, and sweat glands [17, 122, 123]. This unique feature may help to decipher the origin of each component of the HF and offer some clues for the identification of the molecules that regulate the decision of stem cells to enter into different hair lineages and differentiation programmes for each lineage. In contrast to the process of HF morphogenesis, the cellular and molecular mechanisms that control the various morphogenetic events during early organogenesis of sebaceous glands are largely unknown [124].
Our studies showed that the E-M interactions in organogenesis and regeneration of AUs seem to be transient in nature because once antlers have transformed or regenerated from pedicles, physical separation of the two interactive tissue types does not stop antler generation [22] or regeneration [56]. How does this compare with HFs? Are the E-M interactions taking place in the organogenesis and regeneration of HFs also transient?
The close association between velvet epidermis and the PP in the AU does not immediately trigger antler regeneration, but rather the cycles enter a quiescent phase. This is because the endocrine factors (predominately androgens) override the outcome of the E-M interactions to suppress regeneration of antlers. Likewise, the close proximity of the DP and the bulge in HFs does not trigger regeneration of the temporal part of an HF, but the cycle enters a quiescent period called telogen, the length of which varies with species and follicle types. What factors suppress the outcome of the E-M interactions and determine the length of telogen for each HF type? If these overriding factors act in an endocrine or paracrine manner, then we must consider that different hair types may contain different receptors because HFs in different regions on a body have differing lengths of the telogen phase although they share the same systemic milieu. Factors involved in the BMP signalling pathway may also be implicated in this because there is increased activity in BMP signalling pathways to maintain HF stem cells in a quiescent state and these signals must be overcome to promote new tissue growth [116, 119]. Further research is required to clarify this hypothesis.
