10.1371/journal.pgen.1002348
Craig S. Nowell
Craig
S. Nowell
Nicholas Bredenkamp
Nicholas
Bredenkamp
Stéphanie Tetélin
Stéphanie
Tetélin
Xin Jin
Xin
Jin
Christin Tischner
Christin
Tischner
Harsh Vaidya
Harsh
Vaidya
Julie M. Sheridan
Julie
M. Sheridan
Frances Hogg Stenhouse
Frances
Hogg Stenhouse
Raphaela Heussen
Raphaela
Heussen
Andrew J. H. Smith
Andrew
J. H. Smith
C. Clare Blackburn
C.
Clare Blackburn
Foxn1 Regulates Lineage Progression in Cortical and Medullary Thymic Epithelial Cells But Is Dispensable for Medullary Sublineage Divergence
Public Library of Science
2011
foxn1
regulates
lineage
progression
cortical
medullary
thymic
epithelial
cells
dispensable
sublineage
divergence
2011-11-03 00:30:38
Dataset
https://plos.figshare.com/articles/dataset/Foxn1_Regulates_Lineage_Progression_in_Cortical_and_Medullary_Thymic_Epithelial_Cells_But_Is_Dispensable_for_Medullary_Sublineage_Divergence/131838
<div><p>The forkhead transcription factor <em>Foxn1</em> is indispensable for thymus development, but the mechanisms by which it mediates thymic epithelial cell (TEC) development are poorly understood. To examine the cellular and molecular basis of Foxn1 function, we generated a novel and revertible hypomorphic allele of <em>Foxn1</em>. By varying levels of its expression, we identified a number of features of the Foxn1 system. Here we show that Foxn1 is a powerful regulator of TEC differentiation that is required at multiple intermediate stages of TE lineage development in the fetal and adult thymus. We find no evidence for a role for Foxn1 in TEC fate-choice. Rather, we show it is required for stable entry into both the cortical and medullary TEC differentiation programmes and subsequently is needed at increasing dosage for progression through successive differentiation states in both cortical and medullary TEC. We further demonstrate regulation by Foxn1 of a suite of genes with diverse roles in thymus development and/or function, suggesting it acts as a master regulator of the core thymic epithelial programme rather than regulating a particular aspect of TEC biology. Overall, our data establish a genetics-based model of cellular hierarchies in the TE lineage and provide mechanistic insight relating titration of a single transcription factor to control of lineage progression. Our novel revertible hypomorph system may be similarly applied to analyzing other regulators of development.</p> </div>