BMP4 is required for the initial expression of MITF in melanocyte precursor differentiation from embryonic stem cells.
Although the differentiation of melanoblasts to melanocytes is known to depend on many distinct factors, it is still poorly understood which factors lead to the induction of melanoblasts. To determine which factors might induce melanoblasts, we examined a set of candidate factors for their ability to induce expression of MITF, a master regulator of melanoblast development, in an ES cell-based melanocyte differentiation system. It appears that BMP4 is capable of inducing MITF expression in stem cells. In contrast, a number of other factors normally implicated in the development of the melanocyte lineage, including WNT1, WNT3a, SCF, EDN3, IGF1, PDGF, and RA, cannot induce MITF expression. Nevertheless, BMP4 alone does not allow MITF-expressing precursors to become differentiated melanocytes, but the addition of EDN3 further promotes differentiation of the precursors into mature melanocytes. Our results support a model in which BMP4 induces MITF expression in pluripotent stem cells and EDN3 subsequently promotes differentiation of these MITF expressing cells along the melanocyte lineage.
Developmental Cell Biology and Disease Program, School of Ophthalmology and Optometry and Eye Hospital, Wenzhou Medical University, Wenzhou 325003, China; State Key Laboratory Cultivation Base and Key Laboratory of Vision Science of Ministry of Health and Zhejiang Provincial Key Laboratory of Ophthalmology, Wenzhou 325003, China.
Juan
J
Yang
Jing
J
Wang
Li
L
Pan
Huirong
H
Li
Chunbao
C
Rao
Xiaobo
X
Zhang
Guozhen
G
Niu
Jia
J
Qu
Ling
L
Hou
D000818:Animals; D055415:Bone Morphogenetic Protein 4 / Q000378:metabolism*; D002454:Cell Differentiation; D002460:Cell Line; D053595:Embryonic Stem Cells / Q000166:cytology / Q000378:metabolism*; D008544:Melanocytes / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D051739:Microphthalmia-Associated Transcription Factor / Q000096:biosynthesis* / Q000378:metabolism
C525810:Bmp4 protein, mouse; D055415:Bone Morphogenetic Protein 4; D051739:Microphthalmia-Associated Transcription Factor; C497235:Mitf protein, mouse
BMP; Cell lineage; DCT; EBs; EDN3; ES; Fate specification; MITF; Pigment cells; RA; SCF; Signaling; TYRP1; Transcription factor; bFGF; basic fibroblast growth factors; bone morphogenetic protein; dopachrome tautomerase; embryoid bodies; embryonic stem cell; endothelin 3; microphthalmia-associated transcription factor; retinoic acid; stem cell factor; tyrosinase-related protein 1