2 GENETICALLY SEPARABLE STEPS IN THE DIFFERENTIATION OF THYMIC EPITHELIUM

The development oi the thymus depends initially on epithelial-mesenchy mal and subsequently on reciprocal lympho-stromal interactions. The ge netic steps governing development and differentiation of the thymic mi croenvironment are unknown. With the use of a targeted disruption of t he whn gene, which recapitulates the phenotype of the athymic nude mou se, the WHN transcription factor was shown to be the product of the nu de locus. Formation of the thymic epithelial primordium before the ent ry of lymphocyte progenitors did not require the activity of WHN. Howe ver, subsequent differentiation of primitive precursor cells into subc apsular, cortical, and medullary epithelial cells of the postnatal thy mus did depend on activity of the whn gene. These results define the f irst geneticallyd separable steps during thymic epithelial differentia tion.