Loss of Gata6 causes dilation of the hair follicle canal and sebaceous duct

Abstract

The uppermost aspect of the hair follicle, known as the infundibulum or hair canal, provides a passageway for hair shaft egress and sebum secretion. Recent studies have indicated that the infundibulum and sebaceous ducts are lined by molecularly distinct differentiated cells expressing markers including Keratin 79 and Gata6. Here, we ablated Gata6 from the skin and observed dilation of both the hair canal and sebaceous ducts, independent of gender and hair cycle stage. Constitutive loss of Gata6 yielded only a mild delay in depilation-induced entry into anagen, while unperturbed mutant mice possessed overtly normal skin and hair. Furthermore, we noted that Keratin 79 and Gata6 expression and localization did not depend upon each other. Our findings implicate Gata6 in maintaining the upper hair follicle and suggest that regulation of this transcription factor may be compromised in pathologies such as acne or infundibular cystic diseases that are characterized by abnormal expansion of this follicular domain.

Single-cell transcriptome profiling reveals dermal and epithelium cell fate decisions during embryonic hair follicle development

“…Besides, our analysis here also unmasked a series of significantly enriched regulons for the underappreciated IRS (State 1) which included Gata6 , Foxc1 , Jun family members ( Jun , Junb , Jund ), and Klf family members ( Klf3/4/5 ). Noteworthy, Gata6 has been previously demonstrated as a marker for the IRS and perturbation of Gata6 caused dilation of the hair follicle canal demonstrating an indispensable role during hair follicle morphogenesis (Swanson et al, 2019).…”

Contribution of GATA6 to homeostasis of the human upper pilosebaceous unit and acne pathogenesis

“…Retinoids, including isotretinoin, the most effective treatment for acne 25 , are known to stimulate expansion of the progeny of LRIG1+ stem cells and also lead to the upregulation of GATA6 20 , 23 . Upon GATA6 knock-out in KRT5+ keratinocytes, a loss of the ductal cells and a dilation of the INF, JZ, and SD are observed, with cystic lesions filled with keratotic material resembling comedones 23 , 26 . Nevertheless, acne is a disease specific to humans and no animal model recapitulates its pathological features fully.…”

27TH Fondation René Touraine Annual SCIENTIFIC MEETING 2019

“…Combined with the clinical relevance of the SG in the ongoing acne pathobiology debate, which is getting ever more intriguing, [10,84,[87][88][89] The regulatory function of Gata6 seems to extend to the sebaceous duct and the hair canal in murine skin, as reported by Swanson et al. [90] With this wealth of rodent skin SG available now, one would really love to learn how the SG in organ-cultured human skin responds to Gata6 silencing ex vivo, which should be technically possible. [91] Gata6 may also be implicated in the But let us close where we started, that is with an evolutionary perspective.…”