Expression of hedgehog proteins in the human thymus.
The Hedgehog (Hh) family of secreted proteins includes intercellular signaling molecules that specify cell fate and patterning during the development of many tissues. In this study we show that the different components of the Hh signaling pathway are expressed in human thymus. The three mammalian Hh proteins, Sonic (Shh), Indian (Ihh), and Desert (Dhh) hedgehog, are produced by thymic epithelial cells. Shh-expressing epithelial cells are restricted to the thymic subcapsula and medulla, whereas Ihh- and Dhh-producing epithelial cells are distributed throughout the thymus. The requisite Hh receptors, Patched 1(Ptc1) and Smoothened (Smo), and the Gli transcription factors are expressed by thymocytes and also by epithelial cells. Ptc1 is expressed in most thymocyte subsets, whereas Smo expression is mainly associated with immature thymocytes. The isoform of the Ptc receptor, Ptc2, is expressed only by intrathymic progenitor cells and epithelial cells. Other Hh-binding proteins with modulating functions, such as Hedgehog-interacting protein (Hip) and growth arrest-specific gene-1 (Gas-1), are also expressed in human thymus. Our study shows that the intrathymic expression pattern of the Hh signaling pathway components is complex and suggests that Hh proteins may regulate human thymocyte differentiation from the earliest developmental stages, as well as thymic epithelial cell function.
Sacedón
Rosa
R
Department of Cell Biology, Faculty of Medicine, Complutense University, 28040 Madrid, Spain.
Varas
Alberto
A
Hernández-López
Carmen
C
Gutiérrez-deFrías
Cruz
C
Crompton
Tessa
T
Zapata
Agustín G
AG
Vicente
Angeles
A
D002460:Cell Line; D002675:Child, Preschool; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D053823:Hedgehog Proteins; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008565:Membrane Proteins / Q000096:biosynthesis; D015513:Oncogene Proteins / Q000096:biosynthesis; D000072079:Patched Receptors; D000072081:Patched-1 Receptor; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000072086:Smoothened Receptor; D013950:Thymus Gland / Q000378:metabolism*; D015534:Trans-Activators / Q000096:biosynthesis*; D014157:Transcription Factors / Q000096:biosynthesis; D000071676:Zinc Finger Protein GLI1
D053823:Hedgehog Proteins; D008565:Membrane Proteins; D015513:Oncogene Proteins; C000606236:PTCH1 protein, human; D000072079:Patched Receptors; D000072081:Patched-1 Receptor; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; C509239:SHH protein, human; C491023:SMO protein, human; D000072086:Smoothened Receptor; D015534:Trans-Activators; D014157:Transcription Factors; D000071676:Zinc Finger Protein GLI1