Submitted May 22, 2006
Accepted June 12, 2006
Coordination between CCR7- and CCR9-mediated chemokine signals in pre-vascular fetal thymus colonization
Cunlan Liu, Fumi Saito, Zhijie Liu, Yu Lei, Shoji Uehara, Paul Love, Martin Lipp, Shunzo Kondo, Nancy Manley, and Yousuke Takahama*
Division of Experimental Immunology, Institute for Genome Research, University of Tokushima
Department of Genetics, University of Georgia
Laboratory of Mammalian Genes and Development, National Institutes of Health
Department of Molecular Tumorgenetics and Immunogenetics, Max-Delbruk Center for Molecular Medicine
JEOL Ltd
* Corresponding author; email: takahama{at}genome.tokushima-u.ac.jp.
Thymus seeding by T-lymphoid progenitor cells is a prerequisite for T-cell development. However, molecules guiding thymus colonization and their roles before and after thymus vascularization are unclear. Here we show that mice doubly deficient for chemokine receptors CCR7 and CCR9 were defective specifically in fetal thymus colonization before, but not after, thymus vascularization. The defective pre-vascular fetal thymus colonization was followed by selective loss of the first wave of T-cell development generating epidermal V 
3+ 
T cells. Unexpectedly, CCL21, a CCR7 ligand, was expressed not by Foxn1-dependent thymic primordium but by Gcm2-dependent parathyroid primordium, whereas CCL25, a CCR9 ligand, was predominantly expressed by Foxn1-dependent thymic primordium, revealing the role of adjacent parathyroid in guiding fetal thymus colonization. These results indicate coordination between Gcm2-dependent parathyroid and Foxn1-dependent thymic primordia in establishing CCL21/CCR7- and CCL25/CCR9-mediated chemokine guidance essential for pre-vascular fetal thymus colonization.
