Presence and distribution of neural crest-derived cells in the murine developing thymus and their potential for differentiation.

Neural crest (NC) cells are multipotent cells that can differentiate into melanocytes, neurons, glias and myofibroblasts. They migrate into the fetal thymus on embryonic day (E) 12 in mice and may participate in thymic organogenesis. Although the abnormality of migration and distribution of NC cells in the thymus results in immunodeficiency, the spatial and temporal presence of their progeny cells has not been defined in detail. In this study, we traced NC-derived cells based on the myelin protein zero gene promoter-Cre-mediated excision. We demonstrated that large numbers of NC-derived cells in the thymus were detected on E11.5 to E16.5 but rarely on E17.5. A colony formation assay of single thymic cells demonstrated that multipotent cells with the potential to differentiate into melanocytes, neurons and/or glias were present in the E14.5 and E15.5 but not in the E17.5 fetal thymus. Furthermore, we confirmed that these multipotent cells were NC-derived cells. Taken together, these findings imply that multipotent NC-derived cells are present in the developing thymus, but rarely in this organ at a later stage, suggesting that NC-derived cells may play roles in thymic organogenesis at an early embryonic stage.

[1]  N. Manley,et al.  Developing a new paradigm for thymus organogenesis , 2004, Nature Reviews Immunology.

[2]  E. Dupin,et al.  Self-renewal capacity is a widespread property of various types of neural crest precursor cells. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[3]  Howard T. Petrie,et al.  Cell migration and the control of post-natal T-cell lymphopoiesis in the thymus , 2003, Nature Reviews Immunology.

[4]  G. Anderson,et al.  Differential Requirement for Mesenchyme in the Proliferation and Maturation of Thymic Epithelial Progenitors , 2003, The Journal of experimental medicine.

[5]  T. Pietri,et al.  The human tissue plasminogen activator-Cre mouse: a new tool for targeting specifically neural crest cells and their derivatives in vivo. , 2003, Developmental biology.

[6]  N. Manley,et al.  A developmental look at thymus organogenesis: where do the non-hematopoietic cells in the thymus come from? , 2003, Current opinion in immunology.

[7]  Philippe Soriano,et al.  Cell autonomous requirement for PDGFRα in populations of cranial and cardiac neural crest cells , 2003, Development.

[8]  B. Wehrle-Haller,et al.  Molecular identification of distinct neurogenic and melanogenic neural crest sublineages , 2003, Development.

[9]  H. Petrie,et al.  Role of thymic organ structure and stromal composition in steady‐state postnatal T‐cell production , 2002, Immunological reviews.

[10]  I. Gimenez-Conti,et al.  Cutting Edge: Thymocyte-Independent and Thymocyte-Dependent Phases of Epithelial Patterning in the Fetal Thymus1 , 2002, The Journal of Immunology.

[11]  S. Morrison,et al.  Neural Crest Stem Cells Persist in the Adult Gut but Undergo Changes in Self-Renewal, Neuronal Subtype Potential, and Factor Responsiveness , 2002, Neuron.

[12]  G. Holländer,et al.  Generation of a complete thymic microenvironment by MTS24+ thymic epithelial cells , 2002, Nature Immunology.

[13]  Alison Farley,et al.  Identification and characterization of thymic epithelial progenitor cells. , 2002, Immunity.

[14]  F. Vitelli,et al.  Tbx1 mutation causes multiple cardiovascular defects and disrupts neural crest and cranial nerve migratory pathways. , 2002, Human molecular genetics.

[15]  G. Anderson,et al.  Lymphostromal interactions in thymic development and function , 2001, Nature Reviews Immunology.

[16]  H. Kawamoto,et al.  Two distinct steps of immigration of hematopoietic progenitors into the early thymus anlage. , 2001, International immunology.

[17]  H. Etchevers,et al.  The cephalic neural crest provides pericytes and smooth muscle cells to all blood vessels of the face and forebrain. , 2001, Development.

[18]  Birgit Funke,et al.  TBX1 Is Responsible for Cardiovascular Defects in Velo-Cardio-Facial/DiGeorge Syndrome , 2001, Cell.

[19]  N. Manley Thymus organogenesis and molecular mechanisms of thymic epithelial cell differentiation. , 2000, Seminars in immunology.

[20]  J. Epstein,et al.  Migration of cardiac neural crest cells in Splotch embryos. , 2000, Development.

[21]  A. McMahon,et al.  Fate of the mammalian cardiac neural crest. , 2000, Development.

[22]  E. Jenkinson,et al.  An Essential Role for Thymic Mesenchyme in Early T Cell Development , 2000, The Journal of experimental medicine.

[23]  T. Kunisada,et al.  Derivation of melanocytes from embryonic stem cells in culture , 1999, Developmental dynamics : an official publication of the American Association of Anatomists.

[24]  D. Anderson,et al.  In vivo transplantation of mammalian neural crest cells into chick hosts reveals a new autonomic sublineage restriction. , 1999, Development.

[25]  K. Abe,et al.  A novel transgenic technique that allows specific marking of the neural crest cell lineage in mice. , 1999, Developmental biology.

[26]  M. Kirby,et al.  Connexin 43 expression reflects neural crest patterns during cardiovascular development. , 1999, Developmental biology.

[27]  E. Jenkinson,et al.  Factors regulating stem cell recruitment to the fetal thymus. , 1999, Journal of immunology.

[28]  David J. Anderson,et al.  Prospective Identification, Isolation by Flow Cytometry, and In Vivo Self-Renewal of Multipotent Mammalian Neural Crest Stem Cells , 1999, Cell.

[29]  E. Jenkinson,et al.  Studies on the phenotype of migrant thymic stem cells , 1999, European journal of immunology.

[30]  D. Champeval,et al.  Endothelin 3 selectively promotes survival and proliferation of neural crest-derived glial and melanocytic precursors in vitro. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[31]  J. A. Weston,et al.  Timing and pattern of cell fate restrictions in the neural crest lineage. , 1997, Development.

[32]  Philippe Soriano The PDGF alpha receptor is required for neural crest cell development and for normal patterning of the somites. , 1997, Development.

[33]  D. Anderson Cellular and molecular biology of neural crest cell lineage determination. , 1997, Trends in genetics : TIG.

[34]  S. Nishikawa,et al.  PDGFRα Expression During Mouse Embryogenesis: Immunolocalization Analyzed by Whole-mount Immunohistostaining Using the Monoclonal Anti-mouse PDGFRα Antibody APA5 , 1997 .

[35]  G. Anderson,et al.  Fibroblast dependency during early thymocyte development maps to the CD25+ CD44+ stage and involves interactions with fibroblast matrix molecules , 1997, European journal of immunology.

[36]  T. Natoli,et al.  Positive and negative DNA sequence elements are required to establish the pattern of Pax3 expression. , 1997, Development.

[37]  K. Yamamura,et al.  Purification of primordial germ cells from TNAPbeta-geo mouse embryos using FACS-gal. , 1996, Developmental Biology.

[38]  S. Nishikawa,et al.  Distinct stages of melanocyte differentiation revealed by anlaysis of nonuniform pigmentation patterns. , 1996, Development.

[39]  M. Bronner‐Fraser Origins and developmental potential of the neural crest. , 1995, Experimental cell research.

[40]  C. Erickson,et al.  Avian neural crest cells can migrate in the dorsolateral path only if they are specified as melanocytes. , 1995, Development.

[41]  R. Hammer,et al.  Interaction of endothelin-3 with endothelin-B receptor is essential for development of epidermal melanocytes and enteric neurons , 1994, Cell.

[42]  David J. Anderson,et al.  Glial growth factor restricts mammalian neural crest stem cells to a glial fate , 1994, Cell.

[43]  J. Coligan,et al.  Constitutive activation of integrin alpha 4 beta 1 defines a unique stage of human thymocyte development , 1994, The Journal of experimental medicine.

[44]  A. Zlotnik,et al.  A developmental pathway involving four phenotypically and functionally distinct subsets of CD3-CD4-CD8- triple-negative adult mouse thymocytes defined by CD44 and CD25 expression. , 1993, Journal of immunology.

[45]  M. Sieber-Blum,et al.  Pluripotent and developmentally restricted neural-crest-derived cells in posterior visceral arches. , 1993, Developmental biology.

[46]  M. Sieber-Blum,et al.  In vitro clonal analysis of mouse neural crest development. , 1992, Developmental biology.

[47]  I. Jackson,et al.  A second tyrosinase‐related protein, TRP‐2, is a melanogenic enzyme termed DOPAchrome tautomerase. , 1992, The EMBO journal.

[48]  E. Dupin,et al.  Common precursors for neural and mesectodermal derivatives in the cephalic neural crest. , 1991, Development.

[49]  S. Kuratani,et al.  Impaired development of the thymic primordium after neural crest ablation , 1990, The Anatomical record.

[50]  S. Kuratani,et al.  The participation of neural crest derived mesenchymal cells in development of the epithelial primordium of the thymus. , 1990, Archives of histology and cytology.

[51]  S. Nishikawa,et al.  B lymphopoiesis on stromal cell clone: stromal cell clones acting on different stages of B cell differentiation* , 1988, European journal of immunology.

[52]  D. Noden Interactions and fates of avian craniofacial mesenchyme. , 1988, Development.

[53]  M. Bronner‐Fraser Analysis of the early stages of trunk neural crest migration in avian embryos using monoclonal antibody HNK-1. , 1986, Developmental biology.

[54]  M. Kirby,et al.  Neural crest interactions in the development of the immune system. , 1985, Journal of immunology.

[55]  M. Kirby,et al.  Dependence of thymus development on derivatives of the neural crest. , 1984, Science.

[56]  F. Jotereau,et al.  Tracing of cells of the avian thymus through embryonic life in interspecific chimeras , 1975, The Journal of experimental medicine.

[57]  J. Heremans,et al.  Nude Mouse Embryo: Ectodermal Nature of the Primordial Thymic Defect , 1975, Scandinavian journal of immunology.

[58]  T. Mayer,et al.  The migratory pathway of neural crest cells into the skin of mouse embryos. , 1973, Developmental biology.

[59]  S. Hayashi,et al.  Tooth development and tooth regeneration using tooth germ, dental pulp cells, neural crest cells and embryonic stem cells , 2003 .

[60]  T. Kunisada,et al.  Presence of osteoclast precursors in colonies cloned in the presence of hematopoietic colony-stimulating factors. , 2001, Experimental hematology.

[61]  Philippe Soriano Generalized lacZ expression with the ROSA26 Cre reporter strain , 1999, Nature Genetics.

[62]  Chaya Kalcheim,et al.  The Neural Crest: Cell Lineage Segregation During Neural Crest Ontogeny , 1999 .

[63]  S. Nishikawa,et al.  PDGFR alpha expression during mouse embryogenesis: immunolocalization analyzed by whole-mount immunohistostaining using the monoclonal anti-mouse PDGFR alpha antibody APA5. , 1997, The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society.

[64]  G. Anderson,et al.  Cellular interactions in thymocyte development. , 1996, Annual review of immunology.

[65]  N. L. Le Douarin Cell lineage segregation during neural crest ontogeny. , 1990, Annals of the New York Academy of Sciences.

[66]  P. Marks,et al.  Differentiation of normal and neoplastic hematopoietic cells , 1978 .