Interplay between Foxd3 and Mitf regulates cell fate plasticity in the zebrafish neural crest.
Pigment cells of the zebrafish, Danio rerio, offer an exceptionally tractable system for studying the genetic and cellular bases of cell fate decisions. In the zebrafish, neural crest cells generate three types of pigment cells during embryogenesis: yellow xanthophores, iridescent iridophores and black melanophores. In this study, we present evidence for a model whereby melanophores and iridophores descend from a common precursor whose fate is regulated by an interplay between the transcription factors Mitf and Foxd3. Loss of mitfa, a key regulator of melanophore development, resulted in supernumerary ectopic iridophores while loss of foxd3, a mitfa repressor, resulted in fewer iridophores. Double mutants showed a restoration of iridophores, suggesting that one of Foxd3's roles is to suppress mitfa to promote iridophore development. Foxd3 co-localized with pnp4a, a novel marker of early iridophore development, and was necessary for its expression. A considerable overlap was found between iridoblast and melanoblast markers but not xanthoblast markers, which resolved as cells began to differentiate. Cell lineage analyses using the photoconvertible marker, EosFP, revealed that both melanophores and iridophores develop from a mitfa+ precursor. Taken together, our data reveal a Foxd3/mitfa transcriptional switch that governs whether a bi-potent pigment precursor will attain either an iridophore or a melanophore fate.
Curran
Kevin
K
Department of Biology, University of Washington, Seattle, WA 98195-7420, USA.
Lister
James A
JA
Kunkel
Gary R
GR
Prendergast
Andrew
A
Parichy
David M
DM
Raible
David W
DW
D000818:Animals; D030801:Animals, Genetically Modified; D019070:Cell Lineage; D051858:Forkhead Transcription Factors / Q000502:physiology*; D018507:Gene Expression Regulation, Developmental; D008544:Melanocytes / Q000166:cytology; D051739:Microphthalmia-Associated Transcription Factor / Q000502:physiology*; D008856:Microscopy, Fluorescence; D008954:Models, Biological; D008957:Models, Genetic; D009154:Mutation; D009432:Neural Crest / Q000378:metabolism*; D010802:Phylogeny; D010858:Pigmentation; D015027:Zebrafish; D029961:Zebrafish Proteins / Q000502:physiology*
D051858:Forkhead Transcription Factors; D051739:Microphthalmia-Associated Transcription Factor; D029961:Zebrafish Proteins; C491002:foxd3 protein, zebrafish
Dev Biol. 1998 Apr 15;196(2):145-59
9576828
Pigment Cell Res. 1995 Feb;8(1):28-36
7792252
Nat Genet. 1994 Nov;8(3):251-5
7874167
Cell Differ. 1980 Feb;9(1):51-61
7379129
Development. 1999 Sep;126(17):3757-67
10433906
Nature. 2005 Feb 24;433(7028):884-7
15729346
Nat Genet. 1996 Sep;14(1):50-4
8782819
Dev Biol. 2008 May 15;317(2):508-22
18417109
Science. 1979 Feb 2;203(4379):410-5
760198
Annu Rev Genet. 2004;38:365-411
15568981
J Cell Biol. 2002 Sep 16;158(6):1079-87
12235125
Cell. 2009 Oct 16;139(2):366-79
19837037
Dev Biol. 2005 Oct 15;286(2):391-404
16125692
Cell. 1999 Mar 5;96(5):737-49
10089888
Mol Biol Evol. 2006 Jun;23(6):1192-202
16547150
Mech Dev. 2000 May;93(1-2):161-4
10781949
Cell Tissue Res. 1999 Sep;297(3):371-82
10460485
Development. 2001 Nov;128(21):4113-25
11684650
Hum Mol Genet. 2000 Aug 12;9(13):1907-17
10942418
J Biol Chem. 2000 Dec 1;275(48):37978-83
10973953
Biochem Biophys Res Commun. 1996 Jun 25;223(3):514-9
8687427
Semin Cell Dev Biol. 2009 Feb;20(1):105-10
18935965
Dev Biol. 2010 Jun 1;342(1):39-50
20346935
Proc Natl Acad Sci U S A. 2004 Nov 9;101(45):15905-10
15505211
Neuron. 2002 May 16;34(4):577-88
12062041
Dev Biol. 2005 Sep 1;285(1):169-84
16083872
Dev Biol. 2008 Jan 15;313(2):568-83
18068699
Semin Cell Dev Biol. 2009 Feb;20(1):72-81
19073271
Pigment Cell Res. 2000 Apr;13(2):60-9
10841026
Development. 2003 Jun;130(12):2809-18
12736222
J Bacteriol. 1995 Oct;177(19):5506-16
7559336
Development. 2001 Jul;128(13):2525-36
11493569
Cell. 1993 Jul 30;74(2):395-404
8343963
Dev Dyn. 2007 Nov;236(11):3088-99
17937395
Mech Dev. 2001 May;103(1-2):93-106
11335115
J Cell Biol. 1968 Jul;38(1):67-79
5691979
Pigment Cell Res. 2007 Feb;20(1):14-26
17250544
Pigment Cell Res. 2003 Jun;16(3):172-82
12753383
Development. 1997 Jun;124(12):2377-86
9199364
Dev Biol. 2000 Sep 15;225(2):277-93
10985850
Development. 1994 Mar;120(3):495-503
8162850
Dev Biol. 2006 Apr 1;292(1):174-88
16499899
Nat Genet. 1998 Mar;18(3):283-6
9500554
J Biol Chem. 2004 Oct 1;279(40):41911-7
15277526
Dev Biol. 2001 Sep 15;237(2):333-44
11543618
Pigment Cell Res. 2005 Aug;18(4):243-51
16029418
Dev Dyn. 1995 Jul;203(3):253-310
8589427
Methods Cell Biol. 2004;77:505-19
15602929
J Neurosci. 2000 Oct 1;20(19):7370-6
11007895
Hum Genet. 2000 Jul;107(1):1-6
10982026
J Biol Chem. 2007 Jan 26;282(4):2548-57
17138566
Development. 2000 Jul;127(14):3031-44
10862741
Brain Behav Evol. 1992;40(2-3):141-56
1422807
Dev Genes Evol. 1998 Jul;208(5):245-58
9683740
Pigment Cell Res. 2004 Aug;17(4):326-36
15250934
Genes Dev. 2000 Jan 15;14(2):158-62
10652270
J Biol Chem. 2000 Oct 6;275(40):30757-60
10938265
Hum Mol Genet. 1998 Apr;7(4):703-8
9499424
Dev Biol. 2006 Feb 15;290(2):359-72
16386728
Mech Dev. 1998 Aug;76(1-2):185-90
9767163
J Biol Chem. 2000 May 12;275(19):14013-6
10747853
Nat Genet. 2000 Oct;26(2):216-20
11017081
Neuron. 2003 Apr 10;38(1):17-31
12691661
Dev Biol. 2009 Aug 15;332(2):408-17
19527705
PLoS Genet. 2008 Mar 07;4(3):e1000026
18369445
Pharmacol Ther. 2000 Dec;88(3):349-425
11337031
Development. 2009 Jun;136(11):1849-58
19403660
Development. 2006 Dec;133(23):4619-30
17065232
Development. 1996 Dec;123:369-89
9007256
Neuron. 2001 Jan;29(1):57-71
11182081
Dev Biol. 2006 Feb 1;290(1):92-104
16364284