The nu gene acts cell-autonomously and is required for differentiation of thymic epithelial progenitors.

Abstract

The nude mutation (nu) The thymus is the obligatory site of T-cell maturation and is therefore central to the development of a fully competent immune system; athymia results in profound immunodeficiency (1). The thymic epithelium not only supplies a framework in which T-cell development occurs, it also shapes the T-cell repertoire by mediating positive and negative selection of developing thymocytes. Consequently, its organization is quite complex (2).The nude mutation (nu) has a profound effect on thymic development (3, 4) but does not affect the lymphoid compartment (4, 5). During development of the nude thymic anlage, the pharyngeal ectoderm of the third cleft fails to proliferate at embryonic day 11.5 (6) and thymogenesis does not progress beyond this point; the anlage is devoid of lymphocytes and never proceeds to a lymphoid stage (4). Adult nude mice retain a nonfunctional cystic thymic rudiment (7).Two hypotheses have previously been offered to explain the nu defect (6,8

A Putative 12 Transmembrane Domain Cotransporter Expressed in Thymic Cortical Epithelial Cells

“…A Northern blot by us of adult skin and intestinal mRNA failed to detect a signal, but a preliminary experiment with day 14 fetal skin did detect the 1C12 message (data not shown). Thus, similar to the nu gene (22)(23)(24), TSO-1C12 might be expressed in both skin and thymus.…”

Identification of Plet-1 as a specific marker of early thymic epithelial progenitor cells

“…However, its specialist functions reside largely in the diverse array of thymic epithelial cell (TEC) types that form a key component of the thymic stroma (2)(3)(4). Previous work from this and other laboratories has identified and characterized a population of epithelial progenitor cells within the mouse thymic primordium that is sufficient to generate an organized functional thymus containing all TEC subtypes upon ectopic transplantation (5)(6)(7). This population is identified by mAbs MTS20 and MTS24 (5,8).…”

“…Previous work from this and other laboratories has identified and characterized a population of epithelial progenitor cells within the mouse thymic primordium that is sufficient to generate an organized functional thymus containing all TEC subtypes upon ectopic transplantation (5)(6)(7). This population is identified by mAbs MTS20 and MTS24 (5,8). That it contains a common TEPC was initially suggested by the demonstration that the thymus arises solely from the endoderm (9,10) and was recently confirmed by clonal analysis (11,12).…”

Normal Thymic Architecture and Negative Selection Are Associated with Aire Expression, the Gene Defective in the Autoimmune-Polyendocrinopathy-Candidiasis-Ectodermal Dystrophy (APECED)

“…The two tissues are separated by a thin layer of mesenchyme originating from the cephalic neural crest (1). While the relative contribution of each germ layer to the mature thymic epithelial compartment remains to be determined, a small subpopulation of epithelial cells has been characterized that represents a common precursor cell for mature cortical and medullary epithelium (2,3). At day E11.5, hemopoietic precursor cells seed the thymus anlage although its epithelial cells are not yet competent to fully support T cell development (4).…”