4.7 Article

'Cyclic alopecia' in Msx2 mutants: defects in hair cycling and hair shaft differentiation

Journal

DEVELOPMENT
Volume 130, Issue 2, Pages 379-389

Publisher

COMPANY OF BIOLOGISTS LTD
DOI: 10.1242/dev.00201

Keywords

alopecia; hair cycle; hair differentiation; homeobox genes; Msx2; Foxn1; Ha3; Fgf5; mouse

Funding

  1. EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH &HUMAN DEVELOPMENT [T32HD007390] Funding Source: NIH RePORTER
  2. NATIONAL CANCER INSTITUTE [P30CA034196] Funding Source: NIH RePORTER
  3. NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES [R01AR042177, R01AR047364, R01AR043801] Funding Source: NIH RePORTER
  4. NATIONAL INSTITUTE OF DENTAL & CRANIOFACIAL RESEARCH [R01DE011697] Funding Source: NIH RePORTER
  5. NCI NIH HHS [CA34196, P30 CA034196] Funding Source: Medline
  6. NCRR NIH HHS [RR173] Funding Source: Medline
  7. NIAMS NIH HHS [R01 AR042177-05, R01 AR042177-07S1, R01 AR042177-07, AR43801, R01 AR042177, R01 AR047364, R01 AR042177-06, R01 AR042177-06S1, AR47364, R01AR42177] Funding Source: Medline
  8. NICHD NIH HHS [HD07390, T32 HD007390] Funding Source: Medline
  9. NIDCR NIH HHS [R01 DE011697, 1R01DE11697] Funding Source: Medline

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Msx2-deficient mice exhibit progressive hair loss, starting at P14 and followed by successive cycles of wavelike regrowth and loss. During the hair cycle, Msx2 deficiency shortens anagen phase, but, prolongs catagen and telogen. Msx2-deficient hair shafts are structurally abnormal. Molecular analyses suggest a Bmp4/Bmp2/Msx2/Foxn1 acidic hair keratin pathway is involved. These structurally abnormal hairs are easily dislodged in catagen implying a precocious exogen. Deficiency in Msx2 helps to reveal the distinctive skin domains on the same mouse. Each domain cycles asynchronously - although hairs within each skin domain cycle in synchronized waves. Thus, the combinatorial defects in hair cycling and differentiation, together with concealed skin domains, account for the cyclic alopecia phenotype.

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