A domain of Foxn1 required for crosstalk-dependent thymic epithelial cell differentiation

Dong Ming Su; Samuel Navarre; Won Jong Oh; Brian G. Condie; Nancy R. Manley

doi:10.1038/ni983

A domain of Foxn1 required for crosstalk-dependent thymic epithelial cell differentiation

Dong Ming Su, Samuel Navarre, Won Jong Oh, Brian G. Condie, Nancy R. Manley

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63 Scopus citations

Abstract

Thymic epithelial cells (TECs) are required for T cell maturation within the thymus. In the nude (Foxn1^nu/nu) mouse, TECs fail to differentiate. We have generated a hypomorphic allele called Foxn1^Δ, from which an N-terminal domain was deleted. The phenotype was thymus specific, identifying a tissue-specific activity for this domain. Foxn1^Δ/Δ mice showed abnormal thymic architecture, lacking cortical and medullary domains. In contrast to thymi in mice with the null allele, the Foxn1^Δ/Δ thymus promoted T cell development, but with specific defects at both the double-negative and double-positive stages. Thus, initiation and progression of TEC differentiation are genetically separable functions of Foxn1, and the N-terminal domain is required for crosstalk-dependent TEC differentiation.

Original language	English
Pages (from-to)	1128-1135
Number of pages	8
Journal	Nature Immunology
Volume	4
Issue number	11
DOIs	https://doi.org/10.1038/ni983
State	Published - Nov 2003

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@article{4a92f91495e2486da069aa45a6d41332,

title = "A domain of Foxn1 required for crosstalk-dependent thymic epithelial cell differentiation",

abstract = "Thymic epithelial cells (TECs) are required for T cell maturation within the thymus. In the nude (Foxn1nu/nu) mouse, TECs fail to differentiate. We have generated a hypomorphic allele called Foxn1Δ, from which an N-terminal domain was deleted. The phenotype was thymus specific, identifying a tissue-specific activity for this domain. Foxn1Δ/Δ mice showed abnormal thymic architecture, lacking cortical and medullary domains. In contrast to thymi in mice with the null allele, the Foxn1Δ/Δ thymus promoted T cell development, but with specific defects at both the double-negative and double-positive stages. Thus, initiation and progression of TEC differentiation are genetically separable functions of Foxn1, and the N-terminal domain is required for crosstalk-dependent TEC differentiation.",

author = "Su, {Dong Ming} and Samuel Navarre and Oh, {Won Jong} and Condie, {Brian G.} and Manley, {Nancy R.}",

note = "Funding Information: We thank L. Cheng and L. Swart for technical assistance. We thank E. Richie for advice and for reading the manuscript. Embryonic stem cell culture and chimera generation was done by the Medical College of Georgia Transgenic Core Facility. Cell sorting by MoFlo was done by the University of Georgia Flow Cytometry Core Facility. Supported by grants from the National Institutes of Health, Institute of Child Health and Human Development (HD035920) and the Institute of Allergy and Infectious Diseases (AI055001) to N.R.M.",

year = "2003",

month = nov,

doi = "10.1038/ni983",

language = "English",

volume = "4",

pages = "1128--1135",

journal = "Nature Immunology",

issn = "1529-2908",

publisher = "Nature Publishing Group",

number = "11",

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T1 - A domain of Foxn1 required for crosstalk-dependent thymic epithelial cell differentiation

AU - Su, Dong Ming

AU - Navarre, Samuel

AU - Oh, Won Jong

AU - Condie, Brian G.

AU - Manley, Nancy R.

N1 - Funding Information: We thank L. Cheng and L. Swart for technical assistance. We thank E. Richie for advice and for reading the manuscript. Embryonic stem cell culture and chimera generation was done by the Medical College of Georgia Transgenic Core Facility. Cell sorting by MoFlo was done by the University of Georgia Flow Cytometry Core Facility. Supported by grants from the National Institutes of Health, Institute of Child Health and Human Development (HD035920) and the Institute of Allergy and Infectious Diseases (AI055001) to N.R.M.

PY - 2003/11

Y1 - 2003/11

N2 - Thymic epithelial cells (TECs) are required for T cell maturation within the thymus. In the nude (Foxn1nu/nu) mouse, TECs fail to differentiate. We have generated a hypomorphic allele called Foxn1Δ, from which an N-terminal domain was deleted. The phenotype was thymus specific, identifying a tissue-specific activity for this domain. Foxn1Δ/Δ mice showed abnormal thymic architecture, lacking cortical and medullary domains. In contrast to thymi in mice with the null allele, the Foxn1Δ/Δ thymus promoted T cell development, but with specific defects at both the double-negative and double-positive stages. Thus, initiation and progression of TEC differentiation are genetically separable functions of Foxn1, and the N-terminal domain is required for crosstalk-dependent TEC differentiation.

AB - Thymic epithelial cells (TECs) are required for T cell maturation within the thymus. In the nude (Foxn1nu/nu) mouse, TECs fail to differentiate. We have generated a hypomorphic allele called Foxn1Δ, from which an N-terminal domain was deleted. The phenotype was thymus specific, identifying a tissue-specific activity for this domain. Foxn1Δ/Δ mice showed abnormal thymic architecture, lacking cortical and medullary domains. In contrast to thymi in mice with the null allele, the Foxn1Δ/Δ thymus promoted T cell development, but with specific defects at both the double-negative and double-positive stages. Thus, initiation and progression of TEC differentiation are genetically separable functions of Foxn1, and the N-terminal domain is required for crosstalk-dependent TEC differentiation.

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DO - 10.1038/ni983

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VL - 4

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EP - 1135

JO - Nature Immunology

JF - Nature Immunology

IS - 11

ER -

A domain of Foxn1 required for crosstalk-dependent thymic epithelial cell differentiation

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