Biology 133 lecture AY 2021- 2022

As mentioned in the presentation, the four types of hair (guard hair, awl hair, auchene hair, and zigzag hair) are interspersed along the mouse’s body (Panteleyev et al., 2001, as cited in Forni et al., 2012). Additionally, according to Duverger & Morasso (2009), “Hair follicles are found in specific arrays, with large follicles being interspersed by smaller follicles throughout the skin.” This means that the distribution of hair in the mouse’s body is homogenous, with a regular pattern alternating between large and smaller follicles.

To expound upon the frequency and patterning of the mouse coat, the development of the four types of hair follicles has been described to occur in three waves. The first wave of hair follicle induction occurs at around embryonic day 14, with the primary hair placodes producing the guard hair, which represent 1-3% of the total number of hair follicles. This is followed by the second wave of hair follicle induction, which occurs at around embryonic day 16 to 17. In this wave, secondary hair placodes form awl hair, which is 30% of the mouse’s coat. Then, the third and final wave of hair follicle induction produces zigzag hairs from tertiary hair placodes, occurring close to the mouse’s birth. Zigzag hair are the most abundant and constitute about 70% of hair follicles. It is unclear whether auchene hair, which is the least frequently occurring type of hair follicle (~0.1%), is formed during the second wave of hair follicle induction or the third wave. However, all in all, this process results in an organized pattern of hair follicles, with the smaller hair follicles located between large hair follicles.

In addition to the four types of hair follicles, mice also have specialized types of hair: Vibrissae and tail hair. Vibrissae, also known as whiskers, develop within characteristic blood sinuses and are neatly organized, forming a characteristic neuronal aggregation called the ‘cortical barrel.’ Vibrissae start emerging at around embryonic day 12.5, and are already fully emerged by the mouse’s birth. Meanwhile, tail hair forms simultaneously with the secondary wave of coat hair induction, at embryonic day 16.5. The tail contains parallel rings of scale-like structures along its axis, which are separated by a unique type of keratinization. A neatly patterned group of three hairs develop under each scale and emerge through the interscale region (Duverger & Morasso, 2009). These three hair follicles do not form at the same time, with the central hair typically emerging first, followed by the two other hair follicles (Schweizer & Marks, 1977, as cited in Duverger & Morasso, 2009). 

References:

• Duverger, O., & Morasso, M. I. (2009). Epidermal patterning and induction of different hair types during mouse embryonic development. Birth defects research. Part C, Embryo today : reviews, 87(3), 263–272. https://doi.org/10.1002/bdrc.20158
• Forni, M. F., Trombetta-Lima, M., & Sogayar, M. C. (2012). Stem cells in embryonic skin development. Biological research, 45(3), 215–222. https://doi.org/10.4067/S0716-97602012000300003

2. Please elaborate on the mechanism of keratinocyte migration during wound healing and how this eventually leads to wound healing. [Answered by Danica Agtarap]

Keratinocyte migration and proliferation for re-epithelialization is required for a wound to heal successfully. Hours post-injury, keratinocytes release pre-stored IL-1 which activates new cytokines and growth factors such as TNF, TGF, and IL-1, among others. These cytokines and growth factors then act in an autocrine manner such that keratinocytes are induced to go through morphological changes that allow them to become motile and migrate to cover and close the wound area, and also for the expression of new genes (e.g. keratin 6, 16, additional cytokines and growth factors). Additionally, IL-1 and TNF are also responsible for the activation of dermal fibroblasts to induce the production of FGF-7, a growth factor that triggers the inflammatory cascade and is responsible for the stimulation of epithelialization. The activated keratinocytes alert other cells in the epidermis such as epithelial cells to proliferate and differentiate to rebuild the mature stratified epithelium and restore the function of the skin as a barrier. In another case, if the basal layer is not harmed from the injury, the wound area can be closed by the upward migration of basal keratinocytes, similar to keratinocyte migration in non-injured skin. 

References:

• Horst, B., Chouhan, G., Moiemen, N. S., & Grover, L. M. (2018). Advances in keratinocyte delivery in burn wound care. Advanced Drug Delivery Reviews, 123, 18-32. https://doi.org/10.1016/j.addr.2017.06.012
• Michopoulou, A. & Rousselle, P. (2015). How do epidermal matrix metalloproteinases support re-epithelialization during skin healing? European Journal of Dermatology, 25(1). 33-42. doi: 10.1684/ejd.2015.2553

 3. Please explain how sebaceous glands can affect hair loss. [Answered by Lauriz Avenido]

Sebaceous glands are glands producing sebum which functions to lubricate skin against friction. Regression of the sebaceous glands  are reported to be associated with hair loss. An observable decrease in functioning secretory vesicles reduces lipid content. As lipid secretion is involved in hair follicle homeostasis, the absence of sebaceous gland function results in follicle destruction by affecting hair cycle progression and length. Defective cycling or the formation of shorter shafts forms hair follicles that are morphologically abnormal which affects further development and adhesion thus hair loss. 

References:

• Porter, R.M., Jahoda, C.A., Lunny, D.P. Henderson, G. , Ross, J., McLean, W.H., Whittock, N., Wilson, N., Reichelt, J., Magin, T. & Lane, E.B. (2002). Defolliculated (Dfl): a dominant mouse mutation leading to poor sebaceous gland differentiation and total elimination of pelage follicles. J Invest Dermatol, 119, 32-37. doi: 10.1046/j.1523-1747.2002.01806.x.
• Selleri, S., Seltmann, H., Gariboldi, S., Shirai, Y., Balsari, A., Zouboulis, C. & Rumio, C. (2006). Doxorubicin-Induced Alopecia Is Associated with Sebaceous Gland Degeneration. Journal of Investigative Dermatology, 126(4), 711-720. https://doi.org/10.1038/sj.jid.5700175

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Hair follicle development involves various regulatory mechanisms and essential factors. For instance, the induction of primary hair follicles involves the Eda/Edar pathway, which has been identified as the most studied and well-characterized pathway involved in primary hair follicle induction (Mikkola, 2008; Mikkola & Thesleff, 2003, as cited in Duverger & Morasso, 2009). In the same manner, the existence of different types of hair means the existence of various mechanisms and combinations of signaling pathways involved. Thus, with that in mind, the existence and identification of the various hair types would have clinical and cosmetic relevance in determining the regulatory programs on the different hair types. To expound on this, there has been identified medical conditions characterized by the disruption of patterns leading to altered hair growth and distribution, particularly in furry mammals, such as congenital generalized hypertrichosis (Baumeister et al., 1993, as cited in Duverger & Morasso, 2009).  Studying the different types of hair, and identifying the regulatory mechanisms behind them, would aid in the characterization of hair-related defects and allow for better understanding of hair follicle biology at whole. 

Reference:

• Duverger, O., & Morasso, M. I. (2009). Epidermal patterning and induction of different hair types during mouse embryonic development. Birth defects research. Part C, Embryo today : reviews, 87(3), 263–272. https://doi.org/10.1002/bdrc.20158

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