A domain of Foxn1 required for crosstalk-dependent thymic epithelial cell differentiation.
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(Delta), from which an N-terminal domain was deleted. The phenotype was thymus specific, identifying a tissue-specific activity for this domain. Foxn1(Delta/Delta) mice showed abnormal thymic architecture, lacking cortical and medullary domains. In contrast to thymi in mice with the null allele, the Foxn1(Delta/Delta) 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.
Su
Dong-ming
DM
Department of Genetics, Life Sciences Building, University of Georgia, Athens, Georgia 30602, USA.
Navarre
Samuel
S
Oh
Won-jong
WJ
Condie
Brian G
BG
Manley
Nancy R
NR
D000818:Animals; D002454:Cell Differentiation / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D004848:Epithelium / Q000502:physiology; D051858:Forkhead Transcription Factors; D051379:Mice; D009154:Mutation; D017434:Protein Structure, Tertiary; D020239:Receptor Cross-Talk / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology; D013950:Thymus Gland / Q000502:physiology*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
D004268:DNA-Binding Proteins; D051858:Forkhead Transcription Factors; D014157:Transcription Factors; C090140:Whn protein