Sox9 Is Essential for Outer Root Sheath Differentiation and the Formation of the Hair Stem Cell Compartment

Background: The mammalian hair represents an unparalleled model system to understand both developmental processes and stem cell biology. The hair follicle consists of several concentric epithelial sheaths with the outer root sheath (ORS) forming the outermost layer. Functionally, the ORS has been im...

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Published inCurrent biology Vol. 15; no. 15; pp. 1340 - 1351
Main Authors Vidal, Valerie P.I., Chaboissier, Marie-Christine, Lützkendorf, Susanne, Cotsarelis, George, Mill, Pleasantine, Hui, Chi-Chung, Ortonne, Nicolas, Ortonne, Jean-Paul, Schedl, Andreas
Format Journal Article
LanguageEnglish
Published England Elsevier Inc 09.08.2005
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Abstract Background: The mammalian hair represents an unparalleled model system to understand both developmental processes and stem cell biology. The hair follicle consists of several concentric epithelial sheaths with the outer root sheath (ORS) forming the outermost layer. Functionally, the ORS has been implicated in the migration of hair stem cells from the stem cell niche toward the hair bulb. However, factors required for the differentiation of this critical cell lineage remain to be identified. Here, we describe an unexpected role of the HMG-box-containing gene Sox9 in hair development. Results: Sox9 expression can be first detected in the epithelial component of the hair placode but then becomes restricted to the outer root sheath (ORS) and the hair stem cell compartment (bulge). Using tissue-specific inactivation of Sox9, we demonstrate that this gene serves a crucial role in hair differentiation and that skin deleted for Sox9 lacks external hair. Strikingly, the ORS acquires epidermal characteristics with ectopic expression of GATA3. Moreover, Sox9 knock hair show severe proliferative defects and the stem cell niche never forms. Finally, we show that Sox9 expression depends on sonic hedgehog (Shh) signaling and demonstrate overexpression in skin tumors in mouse and man. Conclusions: We conclude that although Sox9 is dispensable for hair induction, it directs differentiation of the ORS and is required for the formation of the hair stem cell compartment. Our genetic analysis places Sox9 in a molecular cascade downstream of sonic hedgehog and suggests that this gene is involved in basal cell carcinoma.
AbstractList BACKGROUNDThe mammalian hair represents an unparalleled model system to understand both developmental processes and stem cell biology. The hair follicle consists of several concentric epithelial sheaths with the outer root sheath (ORS) forming the outermost layer. Functionally, the ORS has been implicated in the migration of hair stem cells from the stem cell niche toward the hair bulb. However, factors required for the differentiation of this critical cell lineage remain to be identified. Here, we describe an unexpected role of the HMG-box-containing gene Sox9 in hair development.RESULTSSox9 expression can be first detected in the epithelial component of the hair placode but then becomes restricted to the outer root sheath (ORS) and the hair stem cell compartment (bulge). Using tissue-specific inactivation of Sox9, we demonstrate that this gene serves a crucial role in hair differentiation and that skin deleted for Sox9 lacks external hair. Strikingly, the ORS acquires epidermal characteristics with ectopic expression of GATA3. Moreover, Sox9 knock hair show severe proliferative defects and the stem cell niche never forms. Finally, we show that Sox9 expression depends on sonic hedgehog (Shh) signaling and demonstrate overexpression in skin tumors in mouse and man.CONCLUSIONSWe conclude that although Sox9 is dispensable for hair induction, it directs differentiation of the ORS and is required for the formation of the hair stem cell compartment. Our genetic analysis places Sox9 in a molecular cascade downstream of sonic hedgehog and suggests that this gene is involved in basal cell carcinoma.
Background: The mammalian hair represents an unparalleled model system to understand both developmental processes and stem cell biology. The hair follicle consists of several concentric epithelial sheaths with the outer root sheath (ORS) forming the outermost layer. Functionally, the ORS has been implicated in the migration of hair stem cells from the stem cell niche toward the hair bulb. However, factors required for the differentiation of this critical cell lineage remain to be identified. Here, we describe an unexpected role of the HMG-box-containing gene Sox9 in hair development. Results: Sox9 expression can be first detected in the epithelial component of the hair placode but then becomes restricted to the outer root sheath (ORS) and the hair stem cell compartment (bulge). Using tissue-specific inactivation of Sox9, we demonstrate that this gene serves a crucial role in hair differentiation and that skin deleted for Sox9 lacks external hair. Strikingly, the ORS acquires epidermal characteristics with ectopic expression of GATA3. Moreover, Sox9 knock hair show severe proliferative defects and the stem cell niche never forms. Finally, we show that Sox9 expression depends on sonic hedgehog (Shh) signaling and demonstrate overexpression in skin tumors in mouse and man. Conclusions: We conclude that although Sox9 is dispensable for hair induction, it directs differentiation of the ORS and is required for the formation of the hair stem cell compartment. Our genetic analysis places Sox9 in a molecular cascade downstream of sonic hedgehog and suggests that this gene is involved in basal cell carcinoma.
The mammalian hair represents an unparalleled model system to understand both developmental processes and stem cell biology. The hair follicle consists of several concentric epithelial sheaths with the outer root sheath (ORS) forming the outermost layer. Functionally, the ORS has been implicated in the migration of hair stem cells from the stem cell niche toward the hair bulb. However, factors required for the differentiation of this critical cell lineage remain to be identified. Here, we describe an unexpected role of the HMG-box-containing gene Sox9 in hair development. Sox9 expression can be first detected in the epithelial component of the hair placode but then becomes restricted to the outer root sheath (ORS) and the hair stem cell compartment (bulge). Using tissue- specific inactivation of Sox9, we demonstrate that this gene serves a crucial role in hair differentiation and that skin deleted for Sox9 lacks external hair. Strikingly, the ORS acquires epidermal characteristics with ectopic expression of GATA3. Moreover, Sox9 knock hair show severe proliferative defects and the stem cell niche never forms. Finally, we show that Sox9 expression depends on sonic hedgehog (Shh) signaling and demonstrate overexpression in skin tumors in mouse and man. We conclude that although Sox9 is dispensable for hair induction, it directs differentiation of the ORS and is required for the formation of the hair stem cell compartment. Our genetic analysis places Sox9 in a molecular cascade downstream of sonic hedgehog and suggests that this gene is involved in basal cell carcinoma.
The mammalian hair represents an unparalleled model system to understand both developmental processes and stem cell biology. The hair follicle consists of several concentric epithelial sheaths with the outer root sheath (ORS) forming the outermost layer. Functionally, the ORS has been implicated in the migration of hair stem cells from the stem cell niche toward the hair bulb. However, factors required for the differentiation of this critical cell lineage remain to be identified. Here, we describe an unexpected role of the HMG-box-containing gene Sox9 in hair development. Sox9 expression can be first detected in the epithelial component of the hair placode but then becomes restricted to the outer root sheath (ORS) and the hair stem cell compartment (bulge). Using tissue-specific inactivation of Sox9, we demonstrate that this gene serves a crucial role in hair differentiation and that skin deleted for Sox9 lacks external hair. Strikingly, the ORS acquires epidermal characteristics with ectopic expression of GATA3. Moreover, Sox9 knock hair show severe proliferative defects and the stem cell niche never forms. Finally, we show that Sox9 expression depends on sonic hedgehog (Shh) signaling and demonstrate overexpression in skin tumors in mouse and man. We conclude that although Sox9 is dispensable for hair induction, it directs differentiation of the ORS and is required for the formation of the hair stem cell compartment. Our genetic analysis places Sox9 in a molecular cascade downstream of sonic hedgehog and suggests that this gene is involved in basal cell carcinoma.
Author Vidal, Valerie P.I.
Ortonne, Jean-Paul
Ortonne, Nicolas
Cotsarelis, George
Mill, Pleasantine
Schedl, Andreas
Hui, Chi-Chung
Lützkendorf, Susanne
Chaboissier, Marie-Christine
Author_xml – sequence: 1
  givenname: Valerie P.I.
  surname: Vidal
  fullname: Vidal, Valerie P.I.
  organization: INSERM U636, Centre de Biochimie, Faculté des Sciences, Parc Valrose, 06108 Nice, France
– sequence: 2
  givenname: Marie-Christine
  surname: Chaboissier
  fullname: Chaboissier, Marie-Christine
  organization: INSERM U636, Centre de Biochimie, Faculté des Sciences, Parc Valrose, 06108 Nice, France
– sequence: 3
  givenname: Susanne
  surname: Lützkendorf
  fullname: Lützkendorf, Susanne
– sequence: 4
  givenname: George
  surname: Cotsarelis
  fullname: Cotsarelis, George
  organization: Department of Dermatology, University of Pennsylvania, Philadelphia, Pennsylvania 19014
– sequence: 5
  givenname: Pleasantine
  surname: Mill
  fullname: Mill, Pleasantine
  organization: Hospital for Sick Children Research Institute, 555 University Avenue, Toronto, Ontario M5G 1X8, Canada
– sequence: 6
  givenname: Chi-Chung
  surname: Hui
  fullname: Hui, Chi-Chung
  organization: Hospital for Sick Children Research Institute, 555 University Avenue, Toronto, Ontario M5G 1X8, Canada
– sequence: 7
  givenname: Nicolas
  surname: Ortonne
  fullname: Ortonne, Nicolas
  organization: Départment de Pathologie, Hôpital Henri Mondor, 94010 Créteil, France
– sequence: 8
  givenname: Jean-Paul
  surname: Ortonne
  fullname: Ortonne, Jean-Paul
  organization: Départment de Dermatologie, Hôpital l’Archet, 06202 Nice, France
– sequence: 9
  givenname: Andreas
  surname: Schedl
  fullname: Schedl, Andreas
  email: schedl@unice.fr
  organization: INSERM U636, Centre de Biochimie, Faculté des Sciences, Parc Valrose, 06108 Nice, France
BackLink https://www.ncbi.nlm.nih.gov/pubmed/16085486$$D View this record in MEDLINE/PubMed
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Snippet Background: The mammalian hair represents an unparalleled model system to understand both developmental processes and stem cell biology. The hair follicle...
The mammalian hair represents an unparalleled model system to understand both developmental processes and stem cell biology. The hair follicle consists of...
BACKGROUNDThe mammalian hair represents an unparalleled model system to understand both developmental processes and stem cell biology. The hair follicle...
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SubjectTerms Alopecia - genetics
Animals
Carcinoma, Basal Cell - metabolism
GATA3 Transcription Factor - metabolism
Gene Expression Regulation, Developmental
Gene Silencing
Hair Follicle - cytology
Hair Follicle - embryology
Hair Follicle - metabolism
Hair Follicle - ultrastructure
Hedgehog Proteins
High Mobility Group Proteins - metabolism
Immunohistochemistry
In Situ Hybridization
Mice
Mice, Transgenic
Microscopy, Electron, Scanning
Signal Transduction - physiology
Skin Neoplasms - metabolism
SOX9 Transcription Factor
Stem Cells - cytology
Stem Cells - metabolism
Trans-Activators - metabolism
Transcription Factors - metabolism
Title Sox9 Is Essential for Outer Root Sheath Differentiation and the Formation of the Hair Stem Cell Compartment
URI https://dx.doi.org/10.1016/j.cub.2005.06.064
https://www.ncbi.nlm.nih.gov/pubmed/16085486
https://search.proquest.com/docview/17654821
https://search.proquest.com/docview/68452840
Volume 15
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