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The role of Lhx2 in hair follicle morphogenesis and regeneration
Umeå University, Faculty of Medicine, Umeå Centre for Molecular Medicine (UCMM). (Leif Carlsson)
2010 (English)Licentiate thesis, comprehensive summary (Other academic)
Abstract [en]

Hair is important for thermoregulation, physical protection, sensory activity, seasonal camouflage and social interactions. Hair is produced in hair follicles (HFs), complex mini-organs in the skin devoted to this task. HFs are formed during embryonic development (morphogenesis) and new hair is continuously generated throughout life since the postnatal HF goes through cycles of regression (catagen), quiescence (telogen) and growth (anagen). The transcriptional regulation of this process is not well understood. The LIM-homeodomain transcription factor Lhx2 has previously been shown to be critically involved in epithelial-mesenchymal interactions during development of various organs and a potent regulator of stem cell function. We therefore elucidated the expression pattern and function of Lhx2 during hair formation.

Lhx2 is expressed during both morphogenesis and anagen in cells scattered in the outer root sheath and in a subpopulation of the matrix cells in the proximal part of the hair bulb. Matrix cells are proliferating progenitor cells that differentiate into the components of the HF including the hair shaft. Expression is turned off during telogen, however Lhx2 expression reappears in the secondary hair germ immediately prior to initiation of the anagen stage. In contrast to previously published results Lhx2 appears to be expressed by progenitor cells distinct from those in the stem cell niche in the bulge region. The developmental-, stage- and cell-specific expression pattern of Lhx2 suggests that Lhx2 is involved in the generation and regeneration of hair.

To test our hypothesis we used different genetically modified mouse strains. First we studied the effect of over-expression of Lhx2 in the HFs using a mouse model where transgenic Lhx2 expression could be induced in dorsal skin. Using this model we could show that Lhx2 expression is sufficient to induce anagen. To analyze the consequence of lack-of-function of Lhx2 we developed a mouse model where it is possible to conditionally inactivate Lhx2 and a mouse strain harbouring a hypomorphic allele of Lhx2. Mice where Lhx2 was conditionally inactivated in postnatal HFs were unable to regrow hair on a shaved area whereas all controls did regrow their hair. The mutant HFs initiated anagen but were unable to produce normal hair shafts. Thus Lhx2 is required for postnatal hair formation. We used the mouse strain carrying a hypomorphic allele of Lhx2 to study the role of Lhx2 during HF morphogenesis. Embryos homozygous for the hypomorphic allele form significantly less HFs compared to control embryos, and the HFs that do form in the mutant embryos appear to be developmentally arrested. These results suggest that Lhx2 is also important during HF morphogenesis. Thus, Lhx2 is an essential positive regulator of hair generation and regeneration.

Place, publisher, year, edition, pages
Umeå: Umeå Centre for Molecular Medicine, Umeå University , 2010. , 49 p.
National Category
Biochemistry and Molecular Biology
Research subject
Molecular Cellbiology
Identifiers
URN: urn:nbn:se:umu:diva-36155OAI: oai:DiVA.org:umu-36155DiVA: diva2:352405
Presentation
2010-09-17, Major Groove, By 6L, Umeå University, Umeå, 09:00 (English)
Supervisors
Available from: 2010-09-27 Created: 2010-09-20 Last updated: 2010-09-27Bibliographically approved
List of papers
1. Cyclic expression of lhx2 regulates hair formation.
Open this publication in new window or tab >>Cyclic expression of lhx2 regulates hair formation.
2010 (English)In: PLoS genetics, ISSN 1553-7404, Vol. 6, no 4, e1000904- p.Article in journal (Refereed) Published
Abstract [en]

Hair is important for thermoregulation, physical protection, sensory activity, seasonal camouflage, and social interactions. Hair is generated in hair follicles (HFs) and, following morphogenesis, HFs undergo cyclic phases of active growth (anagen), regression (catagen), and inactivity (telogen) throughout life. The transcriptional regulation of this process is not well understood. We show that the transcription factor Lhx2 is expressed in cells of the outer root sheath and a subpopulation of matrix cells during both morphogenesis and anagen. As the HFs enter telogen, expression becomes undetectable and reappears prior to initiation of anagen in the secondary hair germ. In contrast to previously published results, we find that Lhx2 is primarily expressed by precursor cells outside of the bulge region where the HF stem cells are located. This developmental, stage- and cell-specific expression suggests that Lhx2 regulates the generation and regeneration of hair. In support of this hypothesis, we show that Lhx2 is required for anagen progression and HF morphogenesis. Moreover, transgenic expression of Lhx2 in postnatal HFs is sufficient to induce anagen. Thus, our results reveal an alternative interpretation of Lhx2 function in HFs compared to previously published results, since Lhx2 is periodically expressed, primarily in precursor cells distinct from those in the bulge region, and is an essential positive regulator of hair formation.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:umu:diva-33655 (URN)10.1371/journal.pgen.1000904 (DOI)000277354200021 ()20386748 (PubMedID)
Available from: 2010-04-30 Created: 2010-04-30 Last updated: 2010-09-27Bibliographically approved

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