Cellular and molecular events during early thymus development.
The thymic stromal compartment consists of several cell types that collectively enable the attraction, survival, expansion, migration, and differentiation of T-cell precursors. The thymic epithelial cells constitute the most abundant cell type of the thymic microenvironment and can be differentiated into morphologically, phenotypically, and functionally separate subpopulations of the postnatal thymus. All thymic epithelial cells are derived from the endodermal lining of the third pharyngeal pouch. Very soon after the formation of a thymus primordium and prior to its vascularization, thymic epithelial cells orchestrate the first steps of intrathymic T-cell development, including the attraction of lymphoid precursor cells to the thymic microenvironment. The correct segmentation of pharyngeal epithelial cells and their subsequent crosstalk with cells in the pharyngeal arches are critical prerequisites for the formation of a thymus anlage. Mutations in several transcription factors and their target genes have been informative to detail some of the complex mechanisms that control the development of the thymus anlage. This review highlights recent findings related to the genetic control of early thymus organogenesis and provides insight into the molecular basis by which lymphocyte precursors are attracted to the thymus.
Holländer
Georg
G
Pediatric Immunology, The Center for Biomedicine, Department of Clinical-Biological Sciences, University of Basel, and The University Children's Hospital of Basel, Basel, Switzerland. georg-a.hollaender@unibas.ch
Gill
Jason
J
Zuklys
Saulius
S
Iwanami
Norimasa
N
Liu
Cunlan
C
Takahama
Yousuke
Y
D000818:Animals; D004062:DiGeorge Syndrome / Q000235:genetics; D051858:Forkhead Transcription Factors / Q000502:physiology; D018507:Gene Expression Regulation, Developmental; D006412:Hematopoietic Stem Cells / Q000166:cytology; D018398:Homeodomain Proteins / Q000502:physiology; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000502:physiology; D051379:Mice; D009687:Nuclear Proteins / Q000502:physiology; D051761:Paired Box Transcription Factors / Q000235:genetics / Q000502:physiology; D017027:Protein Tyrosine Phosphatases / Q000502:physiology; D020825:T-Box Domain Proteins / Q000502:physiology; D013601:T-Lymphocytes / Q000166:cytology / Q000378:metabolism; D013950:Thymus Gland / Q000166:cytology / Q000196:embryology* / Q000378:metabolism
D051858:Forkhead Transcription Factors; D018398:Homeodomain Proteins; C080331:Hoxa3 protein, mouse; D047908:Intracellular Signaling Peptides and Proteins; D009687:Nuclear Proteins; D051761:Paired Box Transcription Factors; C490947:Six1 protein, mouse; D020825:T-Box Domain Proteins; C491573:Tbx1 protein, mouse; C090140:Whn protein; C501156:Eya1 protein, mouse; D017027:Protein Tyrosine Phosphatases