Transcriptome and phenotypic analysis reveals Gata3-dependent signalling pathways in murine hair follicles.
The transcription factor Gata3 is crucially involved in epidermis and hair follicle differentiation. Yet, little is known about how Gata3 co-ordinates stem cell lineage determination in skin, what pathways are involved and how Gata3 differentially regulates distinct cell populations within the hair follicle. Here, we describe a conditional Gata3-/- mouse (K14-Gata3-/-) in which Gata3 is specifically deleted in epidermis and hair follicles. K14-Gata3-/- mice show aberrant postnatal growth and development, delayed hair growth and maintenance, abnormal hair follicle organization and irregular pigmentation. After the first hair cycle, the germinative layer surrounding the dermal papilla was not restored; instead, proliferation was pronounced in basal epidermal cells. Transcriptome analysis of laser-dissected K14-Gata3-/- hair follicles revealed mitosis, epithelial differentiation and the Notch, Wnt and BMP signaling pathways to be significantly overrepresented. Elucidation of these pathways at the RNA and protein levels and physiologic endpoints suggests that Gata3 integrates diverse signaling networks to regulate the balance between hair follicle and epidermal cell fates.
Kurek
Dorota
D
Department of Cell Biology, Erasmus Medical Center, P.O. Box 1738, 3000 DR Rotterdam, The Netherlands.
Garinis
George A
GA
van Doorninck
J Hikke
JH
van der Wees
Jacqueline
J
Grosveld
Frank G
FG
D000818:Animals; D000831:Animals, Newborn; D019485:Bone Morphogenetic Proteins / Q000378:metabolism; D002453:Cell Cycle; D049109:Cell Proliferation; D047108:Embryonic Development; D004817:Epidermis / Q000254:growth & development / Q000378:metabolism; D005260:Female; D005346:Fibroblast Growth Factors / Q000378:metabolism; D050990:GATA3 Transcription Factor / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D018859:Hair Follicle / Q000002:abnormalities / Q000166:cytology / Q000254:growth & development* / Q000378:metabolism*; D017488:Hyperkeratosis, Epidermolytic / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D006965:Hyperplasia; D015603:Keratinocytes / Q000166:cytology / Q000378:metabolism; D007633:Keratins / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D010641:Phenotype; D011247:Pregnancy; D051881:Receptor, Notch1 / Q000378:metabolism; D015398:Signal Transduction; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism; D014158:Transcription, Genetic; D051153:Wnt Proteins / Q000378:metabolism
D019485:Bone Morphogenetic Proteins; D050990:GATA3 Transcription Factor; C494748:Gata3 protein, mouse; C497762:Notch1 protein, mouse; D051881:Receptor, Notch1; D051153:Wnt Proteins; D005346:Fibroblast Growth Factors; D007633:Keratins