Thymopoiesis requires Pax9 function in thymic epithelial cells.
The epithelial thymic anlage develops from the third pharyngeal pouch. Pax9 is expressed in the entire pharyngeal endoderm, and its function is required for normal development of organs derived from pharyngeal pouches. Here, we show that in Pax9 null mice, the thymic anlage develops as an ectopic polyp-like structure in the larynx. It expresses Whn/Foxn1, a marker of thymic epithelium, but fails to perform the normal caudo-ventral movement to the upper mediastinum. The thymic rudiment contains mesenchymal cells, blood vessels and is colonized by T cell progenitors. However, from embryonic day 14.5 onwards, the size of the Pax9 mutant thymus is severely reduced. Whereas expression of TCRbeta chain genes is readily detectable in the mutant thymus, no expression of the TCRgamma chain was detectable. Our results identify a new genetically defined control point of thymopoiesis.
Hetzer-Egger
Claudia
C
Max-Planck-Institut für Immunbiologie, Freiburg, Germany.
Schorpp
Michael
M
Haas-Assenbaum
Annette
A
Balling
Rudi
R
Peters
Heiko
H
Boehm
Thomas
T
D000818:Animals; D015703:Antigens, CD / Q000096:biosynthesis / Q000235:genetics; D002454:Cell Differentiation; D019070:Cell Lineage; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D004847:Epithelial Cells / Q000166:cytology; D005326:Fetal Proteins / Q000096:biosynthesis / Q000235:genetics; D051858:Forkhead Transcription Factors; D018507:Gene Expression Regulation, Developmental; D005865:Gestational Age; D007830:Larynx / Q000196:embryology; D008482:Mediastinum / Q000196:embryology; D051379:Mice; D018345:Mice, Knockout; D009024:Morphogenesis; D051764:PAX9 Transcription Factor; D010614:Pharynx / Q000196:embryology; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000096:biosynthesis / Q000235:genetics; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000096:biosynthesis / Q000235:genetics; D013047:Specific Pathogen-Free Organisms; D016176:T-Lymphocyte Subsets / Q000166:cytology* / Q000378:metabolism; D013950:Thymus Gland / Q000166:cytology / Q000196:embryology*; D014157:Transcription Factors / Q000096:biosynthesis / Q000172:deficiency / Q000235:genetics / Q000502:physiology*
D015703:Antigens, CD; D004268:DNA-Binding Proteins; D005326:Fetal Proteins; D051858:Forkhead Transcription Factors; D051764:PAX9 Transcription Factor; D016693:Receptors, Antigen, T-Cell, alpha-beta; D016692:Receptors, Antigen, T-Cell, gamma-delta; D014157:Transcription Factors; C090140:Whn protein