Evidence map›Paper›PMID 41075928›Full record

ArticleThe Journal of investigative dermatology2026

KCTD1/KCTD15-Mediated Repression of AP-2α/AP-2β Is Required for Proper Skin Appendage Development and Epidermal Homeostasis.

Bill Senapati, Jackelyn R Raymundo, Jasson Makkar, Ryan R Driskell, Alexander G Marneros

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in The Journal of investigative dermatology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

5 authors.

Bill SenapatiCutaneous Biology Research Center, Department of Dermatology, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts, USA.
Jackelyn R RaymundoCutaneous Biology Research Center, Department of Dermatology, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts, USA.
Jasson MakkarSchool of Molecular Biosciences, Washington State University, Pullman, Washington, USA; Center for Reproductive Biology, College of Veterinary Medicine, Washington State University, Pullman, Washington, USA.
Ryan R DriskellSchool of Molecular Biosciences, Washington State University, Pullman, Washington, USA; Center for Reproductive Biology, College of Veterinary Medicine, Washington State University, Pullman, Washington, USA.
Alexander G MarnerosCutaneous Biology Research Center, Department of Dermatology, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts, USA. Electronic address: amarneros@mgh.harvard.edu.

Funding

Cellular and molecular mechanisms of AIM2 and NLRP3 inflammasome activation in age-related macular degenerationR01EY033709 · NEI · MASSACHUSETTS GENERAL HOSPITAL · PI Alexander Georg Marneros · 2023 to 2026
$2.0M
Functional characterization of a novel key regulator of the distal nephron whose deficiency leads to renal fibrosis and cyst formationR01DK118134 · NIDDK · MASSACHUSETTS GENERAL HOSPITAL · PI MARNEROS, ALEXANDER GEORG · 2019 to 2023
$1.7M
Proangiogenic M2-type macrophages and choroidal neovascularizationR01EY033360 · NEI · MASSACHUSETTS GENERAL HOSPITAL · PI Alexander Georg Marneros · 2022 to 2026
$1.7M
Mechanisms controlling distal nephron maturationR01DK121178 · NIDDK · MASSACHUSETTS GENERAL HOSPITAL · PI MARNEROS, ALEXANDER GEORG · 2019 to 2022
$1.4M
Role of KCTD1 for primary hyperparathyroidismR21AG063377 · NIA · MASSACHUSETTS GENERAL HOSPITAL · PI MARNEROS, ALEXANDER GEORG · 2019 to 2020
$436k
NEI NIH HHS R01 EY033360NEI NIH HHS R01 EY033709NIA NIH HHS R21 AG063377NIDDK NIH HHS R01 DK118134NIDDK NIH HHS R01 DK121178
6 · The paper itself

Abstract

The transcriptional regulation of skin appendage morphogenesis during development is poorly understood. We identified a previously unknown critical role of KCTD1/KCTD15 complexes in keratinocytes for the proper formation of skin appendages. Individuals with dominant-negative mutations in KCTD1/KCTD15 have sparse hair and anhidrosis, and mice lacking KCTD1 and KCTD15 in keratinocytes have diminished sweat glands and sebaceous glands as well as progressive hair sparseness. In this study, we show that these phenotypes are a consequence of the lack of the repressor function of KCTD1/KCTD15 complexes on AP-2α and AP-2β transcription factors in keratinocytes. Countering the derepression of AP-2α/AP-2β by heterozygosity for their genes rescues skin appendage defects in mice lacking KCTD1/KCTD15 in keratinocytes. Strikingly, loss of AP-2α and AP-2β in keratinocytes results in similar abnormalities, demonstrating that both an increase and a decrease in AP-2α/AP-2β activity impairs skin appendage development. In addition, we find that KCTD1/KCTD15-mediated repression of AP-2α/AP-2β in keratinocytes maintains epidermal homeostasis in the adult and that a dermatitis caused by deficiency of AP-2α in keratinocytes can be prevented by inactivation of KCTD1/KCTD15 complexes. Collectively, our findings identify a critical role of KCTD1/KCTD15 complexes in regulating skin appendage morphogenesis and epidermal homeostasis by repressing AP-2α/AP-2β transcription factors in keratinocytes.

Indexed as

EpidermisTranscription Factor AP-2AnimalsGene Expression Regulation, DevelopmentalHomeostasisHumansKeratinocytesMiceMice, KnockoutSkinTranscription Factor AP-2AP-2Eccrine sweat glandsHair folliclesSebaceous glandsSkin appendages

Identifiers

PMID41075928
PMCPMC12798822

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.