Michael Nehls, ^* Bruno Kyewski, Martin Messerle, Ralph Waldschütz, Kerstin Schüddekopf, Andrew J. H. Smith, ^§ Thomas Boehm

The development of the thymus depends initially on epithelial-mesenchymal and subsequently on reciprocal lympho-stromal interactions. The genetic steps governing development and differentiation of the thymic microenvironment are unknown. With the use of a targeted disruption of the whn gene, which recapitulates the phenotype of the athymic nude mouse, the WHN transcription factor was shown to be the product of the nude locus. Formation of the thymic epithelial primordium before the entry of lymphocyte progenitors did not require the activity of WHN. However, subsequent differentiation of primitive precursor cells into subcapsular, cortical, and medullary epithelial cells of the postnatal thymus did depend on activity of the whn gene. These results define the first genetically separable steps during thymic epithelial differentiation.

M. Nehls, B. Kyewski, M. Messerle, R. Waldschütz, K. Schüddekopf, T. Boehm, Deutsches Krebsforschungszentrum, Im Neuenheimer Feld 280, 69120 Heidelberg, Germany.
A. J. H. Smith, MRC Laboratory of Molecular Biology, Hills Road, Cambridge CB2 2QH, UK.
^* Present address: Zentrum der Inneren Medizin-Molekulare Kardiologie, Universität Frankfurt, 60590 Frankfurt, Germany.
Present address: Institut für Virologie, Universität Heidelberg, Heidelberg, Germany.
Present address: Institut für Humangenetik, Universität Hamburg, 22529 Hamburg, Germany.
^§ Present address: Center of Genome Research, University of Edinburgh, Edinburgh EH9 3JQ, UK.
To whom correspondence should be addressed. E-mail: t.boehm{at}dkfz-heidelberg.de