Thymopoiesis in mice depends on a Foxn1-positive thymic epithelial cell lineage.
The thymus is essential for T-cell development. Here, we focus on the role of the transcription factor Foxn1 in the development and function of thymic epithelial cells (TECs) of the mouse. TECs are of endodermal origin; they initially express Foxn1 and give rise to orthotopic (thoracic) and additional (cervical) thymi. Using Foxn1-directed cytoablation, we show that during embryogenesis, cervical thymi develop a few days after the thoracic lobes, and that bipotent epithelial progenitors of cortical and medullary compartments express Foxn1. We also show that following acute selective near-total ablation during embryogenesis, complete regeneration of TECs does not occur, providing an animal model for human thymic aplasia syndromes. Finally, we address the functional role of Foxn1-negative TECs that arise postnatally in the mouse. Lineage tracing shows that such Foxn1-negative TECs are descendants of Foxn1-positive progenitors; furthermore, Foxn1-directed subacute intoxication of TECs by polyglutamine-containing EGFP proteins indicates that a presumptive Foxn1-independent lineage does not contribute to thymopoietic function of the adult thymus. Our findings therefore support the notion that Foxn1 is the essential transcription factor regulating the differentiation of TECs and that its expression marks the major functional lineage of TECs in embryonic and adult thymic tissue.
Corbeaux
Tatiana
T
Max-Planck Institute of Immunobiology, Freiburg D-79108, Germany.
Hess
Isabell
I
Swann
Jeremy B
JB
Kanzler
Benoît
B
Haas-Assenbaum
Annette
A
Boehm
Thomas
T
D000818:Animals; D001483:Base Sequence; D017931:DNA Primers / Q000235:genetics; D053595:Embryonic Stem Cells / Q000166:cytology / Q000378:metabolism; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism; D005260:Female; D051858:Forkhead Transcription Factors / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D038041:Lymphopoiesis / Q000235:genetics / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D011247:Pregnancy; D013950:Thymus Gland / Q000002:abnormalities / Q000166:cytology / Q000196:embryology* / Q000378:metabolism
D017931:DNA Primers; D051858:Forkhead Transcription Factors; C090140:Whn protein
J Immunol. 2005 Oct 15;175(8):5213-21
16210626
Nat Immunol. 2003 Nov;4(11):1128-35
14528302
Science. 2006 Apr 14;312(5771):284-7
16513945
J Immunol. 2008 Oct 15;181(8):5272-7
18832682
J Immunol. 2008 Nov 1;181(9):6101-8
18941199
World J Surg. 2000 Nov;24(11):1330-4
11038202
Annu Rev Immunol. 2008;26:355-88
18304000
BMC Dev Biol. 2001;1:4
11299042
J Immunol. 2006 Jun 1;176(11):6484-90
16709805
Nature. 1993 Mar 4;362(6415):70-3
8446171
Nature. 2006 Jun 22;441(7096):992-6
16791198
Blood. 2006 Dec 1;108(12):3777-85
16896157
Mech Dev. 2001 May;103(1-2):141-3
11335122
Nat Protoc. 2008;3(6):948-54
18536643
J Biol Chem. 2010 Feb 19;285(8):5836-47
19955175
Nature. 1994 Nov 3;372(6501):103-7
7969402
Nature. 2006 Jun 22;441(7096):988-91
16791197
Int Immunol. 2007 Feb;19(2):127-32
17158094
Curr Opin Immunol. 2008 Apr;20(2):178-84
18403191
Dev Biol. 2005 Feb 15;278(2):323-35
15680353
Dev Biol. 2007 May 1;305(1):333-46
17382312
EMBO J. 2004 Oct 27;23(21):4307-18
15470501
Science. 1996 May 10;272(5263):886-9
8629026
Dev Biol. 2009 Mar 1;327(1):216-27
19135046
Nat Biotechnol. 2001 Aug;19(8):746-50
11479567
Histopathology. 1992 Dec;21(6):499-511
1468748
Trends Neurosci. 2008 Oct;31(10):521-8
18778858
Mech Dev. 1999 Dec;89(1-2):215-21
10559501
Scand J Immunol. 2007 Jul;66(1):1-7
17587340