Back to Search
Start Over
Transcription Factor PAX6 (Paired Box 6) Controls Limbal Stem Cell Lineage in Development and Disease
- Source :
- The Journal of biological chemistry, vol 290, iss 33
- Publication Year :
- 2015
- Publisher :
- Elsevier BV, 2015.
-
Abstract
- PAX6 is a master regulatory gene involved in neuronal cell fate specification. It also plays a critical role in early eye field and subsequent limbal stem cell (LSC) determination during eye development. Defects in Pax6 cause aniridia and LSC deficiency in humans and the Sey (Small eye) phenotype in mice (Massé, K., Bhamra, S., Eason, R., Dale, N., and Jones, E. A. (2007) Nature 449, 1058-1062). However, how PAX6 specifies LSC and corneal fates during eye development is not well understood. Here, we show that PAX6 is expressed in the primitive eye cup and later in corneal tissue progenitors in early embryonic development. In contrast, p63 expression commences after that of PAX6 in ocular adnexal and skin tissue progenitors and later in LSCs. Using an in vitro feeder-free culture system, we show that PAX6 knockdown in LSCs led to up-regulation of skin epidermis-specific keratins concomitant with differentiation to a skin fate. Using gene expression analysis, we identified the involvement of Notch, Wnt, and TGF-β signaling pathways in LSC fate determination. Thus, loss of PAX6 converts LSCs to epidermal stem cells, as demonstrated by a switch in the keratin gene expression profile and by the appearance of congenital dermoid tissue.
- Subjects :
- PAX6 Transcription Factor
genetic structures
Cellular differentiation
Eye
Medical and Health Sciences
Biochemistry
Cornea
Mice
Stem Cell Research - Nonembryonic - Human
Limbic System
2.1 Biological and endogenous factors
Paired Box Transcription Factors
Limbal stem cell
Aetiology
transcription factor
Skin
Genetics
integumentary system
Stem Cells
Wnt signaling pathway
Biological Sciences
Cell biology
Stem Cell Research - Nonembryonic - Non-Human
Development of treatments and therapeutic interventions
Stem cell
Signal Transduction
Biochemistry & Molecular Biology
endocrine system
1.1 Normal biological development and functioning
Cell fate determination
Biology
stem cells
Underpinning research
Animals
Humans
Cell Lineage
Progenitor cell
Eye Proteins
Eye Disease and Disorders of Vision
Molecular Biology
Homeodomain Proteins
5.2 Cellular and gene therapies
Gene Expression Profiling
Membrane Proteins
Cell Biology
Stem Cell Research
eye diseases
Repressor Proteins
cell differentiation
Chemical Sciences
Eye development
sense organs
PAX6
Subjects
Details
- ISSN :
- 00219258
- Volume :
- 290
- Database :
- OpenAIRE
- Journal :
- Journal of Biological Chemistry
- Accession number :
- edsair.doi.dedup.....951bd24dcd4326b0b62a5c3937cd2a9f