Sexual selection has been proposed as one mechanism to explain the maintenance of high allelic diversity in MHC genes that control the extent of resistance against pathogens and parasites in natural populations. MHC-based sexual selection is known to involve olfactory mechanisms in fish, mice, and humans. During mate choice, females of the three-spined stickleback (Gasterosteus aculeatus) use an odor-based selection strategy to achieve an optimal level of MHC diversity in their offspring, equipping them with optimal resistance toward pathogens and parasites. The molecular mechanism of odor-based mate-selection strategies is unknown. Because peptide ligands for MHC class I molecules function as individuality signals in mice, we hypothesized that female sticklebacks might assess the degree of MHC diversity of potential partners by means of the structural diversity of the corresponding peptide ligands in perceived odor signals. We show that structurally diverse MHC ligands interact with natural odors of male sticklebacks to predictably modify MHC-related mate choice. For a mating pair with suboptimal numbers of MHC alleles, peptides increase the attractiveness of male water, whereas for a mating pair with superoptimal numbers, attractiveness is decreased. Our results suggest that female sticklebacks use evolutionarily conserved structural features of MHC peptide ligands to evaluate MHC diversity of their prospective mating partners.sexual selection ͉ olfaction ͉ immunogenetics T he maintenance of high allelic diversity in MHC genes that control the extent of resistance against pathogens and parasites in natural populations has been explained by sexual selection (1, 2). MHC-based sexual selection is known to involve olfactory mechanisms in fish (3, 4), mice (5-7), and humans (8, 9). In natural populations of the three-spined stickleback (Gasterosteus aculeatus), individuals with an intermediate number of different MHC alleles are the most frequent genotype (3, 10) that both under field (10) and experimental conditions (11, 12) best resist natural parasites. During mate choice, female sticklebacks use an odor-based selection strategy to achieve this optimal level of MHC diversity in their offspring (3, 4). Therefore, male sticklebacks are postulated to produce and release MHC-related odors that provide information about the individual's composition of MHC alleles. It is also clear that, although the mechanism is as yet unknown, female sticklebacks are capable of assessing the degree of MHC diversity of their prospective mating partners. Because genes of the MHC complex are highly polymorphic and encode structurally related but distinct MHC molecules (13,14), natural chemosignals that function in MHC-related mate choice must be expected also to be structurally polymorphic, and the extent of their structural diversity should be a function of the number of structurally different MHC molecules expressed by an individual. With regard to the nature of this signal, MHC molecules or their fragments, degradation products of t...

The thymus is essential for T-cell development. Here, we focus on the role of the transcription factor Foxn1 in the development and function of thymic epithelial cells (TECs) of the mouse. TECs are of endodermal origin; they initially express Foxn1 and give rise to orthotopic (thoracic) and additional (cervical) thymi. Using Foxn1-directed cytoablation, we show that during embryogenesis, cervical thymi develop a few days after the thoracic lobes, and that bipotent epithelial progenitors of cortical and medullary compartments express Foxn1. We also show that following acute selective near-total ablation during embryogenesis, complete regeneration of TECs does not occur, providing an animal model for human thymic aplasia syndromes. Finally, we address the functional role of Foxn1-negative TECs that arise postnatally in the mouse. Lineage tracing shows that such Foxn1-negative TECs are descendants of Foxn1-positive progenitors; furthermore, Foxn1-directed subacute intoxication of TECs by polyglutamine-containing EGFP proteins indicates that a presumptive Foxn1-independent lineage does not contribute to thymopoietic function of the adult thymus. Our findings therefore support the notion that Foxn1 is the essential transcription factor regulating the differentiation of TECs and that its expression marks the major functional lineage of TECs in embryonic and adult thymic tissue.epithelium | progenitor cell | thymus | mouse

The thymus is a lymphoid organ unique to vertebrates, and it provides a unique microenvironment that facilitates the differentiation of immature hematopoietic precursors into mature T cells. We subjected the evolutionary trajectory of the thymic microenvironment to experimental analysis. A hypothetical primordial form of the thymus was established in mice by replacing FOXN1, the vertebrate-specific master regulator of thymic epithelial cell function, with its metazoan ancestor, FOXN4, thereby resetting the regulatory and coding changes that have occurred since the divergence of these two paralogs. FOXN4 exhibited substantial thymopoietic activity. Unexpectedly, histological changes and a functional imbalance between the lymphopoietic cytokine IL7 and the T cell specification factor DLL4 within the reconstructed thymus resulted in coincident but spatially segregated T and B cell development. Our results identify an evolutionary mechanism underlying the conversion of a general lymphopoietic organ to a site of exclusive T cell generation.

The analysis of chimeras has shown that communication between germ-line and soma cells plays an important role during Drosophila oogenesis. We have therefore investigated the intercellular exchange of the fluorescent tracer molecule, Lucifer yellow, pressure-injected into the oocyte of vitellogenic follicles of Drosophila. The dye reached the nurse cells via cytoplasmic bridges and entered, via gap junctions, the somatic follicle cells covering the oocyte. The percentage of follicles showing dye-coupling between oocyte and follicle cells was found to increase with the developmental stage up to stage 11, but depended also on the status of oogenesis, i.e., the stage-spectrum, in the respective ovary. During late stage 10B and stage 11, dye-coupling was restricted to the follicle cells covering the anterior pole of the oocyte. No dye-coupling was observed from stage 12 onwards. During prolonged incubation in vitro, the dye was found to move from the follicle cells back into the oocyte; this process was suppressable with dinitrophenol. Dye-coupling was inhibited when prolonged in vitro incubation preceded the dye-injection. Moreover, dye-coupling was inhibited with acidic pH, low [K+], high intracellular [Ca2+], octanol, dinitrophenol, and NaN3, but not with retinoic acid, basic pH, or high extracellular [Ca2+]. Dye-coupling was stimulated with a juvenile hormone analogue and with 20-hydroxyecdysone. Thus, gap junctions between oocyte and follicle cells may play an important role in intercellular communication during oogenesis. We discuss the significance of our findings with regard to the electrophysiological properties of the follicles, and to the coordinated activities of the different cell types during follicle development and during the establishment of polarity in the follicle.

The cloning and characterization of the zebrafish orthologue of the mouse nude (Whn/Foxn1) gene, whnb are reported. A previously described Whn-like gene from zebrafish, now designated as whna, is shown to be the orthologue of the mouse Foxn4 gene. The whnb gene is specifically expressed in the thymic rudiment of zebrafish embryos at day 3 after fertilization, whereas the whna gene is expressed in eye and brain structures. Whnb expression is maintained in cloche mutants, where endothelial and haematopoietic cell differentiation is defective, but absent in casanova mutants where endoderm formation is impaired. In adult thymi, whnb is expressed throughout cortical and medullary areas, whereas whna expression is observed in rare cell clusters only. Our results provide the first specific marker for the epithelial compartment of the zebrafish thymus.