Advertisement
JOURNAL ARTICLES
Spatial and temporal patterns of c-kit-expressing cells in WlacZ/+ and WlacZ/WlacZ mouse embryos
F. Bernex, P. De Sepulveda, C. Kress, C. Elbaz, C. Delouis, J.J. Panthier
Development 1996 122: 3023-3033;

Summary

In the mouse, the Kit receptor and its ligand, the stem cell factor (SCF), are encoded at the W/Kit and Steel loci, respectively. The Kit/SCF transduction pathway is involved in promoting cellular migration, proliferation and/or survival of melanoblasts, hematopoietic progenitors and primordial germ cells. Furthermore, a functional Kit/SCF pathway is required for the development of interstitial cells of Cajal (ICC) in the small intestine. Whereas all c-kit-expressing cells in embryogenesis were not identified, previous studies clearly demonstrated that the c-kit expression pattern extends well beyond cells known to be affected by W mutations. To investigate further Kit function, we specifically marked the c-kit-expressing cells and followed their fate during embryogenesis. A mutation was introduced by gene targeting at the W/Kit locus in mouse embryonic stem cells. The lacZ reporter gene was inserted into the first exon of c-kit, thus creating a null allele, called WlacZ. The lacZ expression reflects normal expression of the c-kit gene in WlacZ/+ embryos. The comparison of the patterns of lacZ-expressing cells between WlacZ/+ and WlacZ/WlacZ embryos allowed us to detect where and when melanoblasts, primordial germ cells and hematopoietic progenitors failed to survive in the absence of Kit. We also observed that ICC express c-kit during embryogenesis. ICC are found identically in WlacZ/+ and WlacZ/WlacZ embryos. Therefore, ICC do not depend on Kit expression during embryogenesis. These results indicate that the function of the c-kit gene is only required for the postnatal development of the ICC. Unexpected sites of c-kit expression were uncovered in embryos, including endothelial, epithelial and endocrine cells. None of these cells are dependent on Kit expression for their migration, proliferation and/or survival during embryogenesis. Nevertheless, we assume that the Kit/SCF pathway could be involved in the growth of transformed endothelial, epithelial and endocrine cells.

Reference

    1. Broudy V. C.,
    2. Kovach N. L.,
    3. Bennett L. G.,
    4. Lin N.,
    5. Jacobsen F. W.,
    6. Kidd P.G.
    (1994) Human umbilical vein endothelial cells display high-affinity c- kit receptors and produce a soluble form of the c- kit receptor. Blood 83, 2145–2152
    OpenUrlAbstract/FREE Full Text
    1. Buehr M.,
    2. McLaren A.,
    3. Bartley A.,
    4. Darling S.
    (1993) Proliferation and migration of primordial germ cells in We / We mouse embryos. Develop. Dynam 198, 182–189
    OpenUrlPubMedWeb of Science
    1. Buzby J. S.,
    2. Knoppel E. M.,
    3. Cairo M. S.
    (1994) Coordinate regulation of Steel Factor, its receptor (Kit), and cytoadhesion molecule (ICAM-1 and ELAM-1) mRNA expression in human vascular endothelial cells of differing origins. Exp. Hematol 22, 122–129
    OpenUrlPubMedWeb of Science
    1. Cable J.,
    2. Jackson I. J.,
    3. Steel K. P.
    (1995) Mutations at the W locus affect survival of neural crest-derived melanocytes in the mouse. Mech. Develop 50, 139–150
    OpenUrlCrossRefPubMedWeb of Science
    1. Colucci-Guyon E.,
    2. Portier M.-M.,
    3. Dunia I.,
    4. Paulin D.,
    5. Pournin S.,
    6. Babinet C.
    (1994) Mice lacking vimentin develop and reproduce without an obvious phenotype. Cell 79, 679–694
    OpenUrlCrossRefPubMedWeb of Science
    1. De Sepulveda P.,
    2. Peyrieras N.,
    3. Panthier J.-J.
    (1994) Instability at the W /c- kit locus in mice: analysis of melanocyte cell lines derived from reversion spots. Oncogene 9, 2655–2661
    OpenUrlPubMed
    1. De Sepulveda P.,
    2. Salaun P.,
    3. Maas N.,
    4. Andre C.,
    5. Panthier J.-J.
    (1995) SARs do not impair position-dependent expression of a Kit/lacZ transgene. Biochem. Biophys. Res. Commun 211, 735–741
    OpenUrlCrossRefPubMedWeb of Science
    1. Dieterlen-Lievre F.,
    2. Le Douarin N. M.
    (1993) Developmental rules inthe hematopoietic and immune systems of birds: how general are they?. Dev. Biol 4, 325–332
    OpenUrlCrossRef
    1. Dorfam D. M.,
    2. Wilson D. B.,
    3. Bruns G. A.,
    4. Orkin S. H.
    (1992) Human transcription factor GATA-2. Evidence for regulation of preproendothelin-1 gene expression in endothelial cells. J. Biol. Chem 267, 1279–.
    OpenUrlAbstract/FREE Full Text
    1. Dumont D. J.,
    2. Gradwohl G. J.,
    3. Fong G.-H.,
    4. Puri M. C.,
    5. Gertsenstein M.,
    6. Auerbach A.,
    7. Breitman M. L.
    (1994) Dominant-negative and targeted null mutations in the endothelial receptor tyrosine kinase, tek, reveal a critical role in vasculogenesis of the embryo. Genes Dev 8, 1897–1909
    OpenUrlAbstract/FREE Full Text
    1. Faussone-Pelligrini M. S.
    (1984) Morphogenesis of the special circular muscle layer and of the interstitial cells of Cajal related to the plexus muscularis profundus of mouse intestinal muscle coat. An E.M. study. Anat. Embryol 169, 151–158
    OpenUrlCrossRefPubMed
    1. Faussone-Pelligrini M. S.
    (1985) Cytodifferentiation of the interstitial cells of Cajal related to the myenteric plexus of mouse intestinal muscle coat. An E.M. study from foetal to adult life. Anat. Embryol 171, 163–169
    OpenUrlCrossRefPubMed
    1. Fleischman R. A.,
    2. Mintz B.
    (1979) Prevention of genetic anemias in mice by microinjection of normal hematopoietic stem cells into the fetal placenta. Proc. Natl. Acad. Sci. U.S.A 76, 5736–5740
    OpenUrlAbstract/FREE Full Text
    1. Fong G.-H.,
    2. Rossant J.,
    3. Gertsenstein M.,
    4. Breitman M. L.
    (1995) Role of the Flt-1 receptor tyrosine kinase in regulating the assembly of vascular endothelium. Nature 376, 66–70
    OpenUrlCrossRefPubMed
    1. Galli S. J.,
    2. Zsebo K. M.,
    3. Geissler E. N.
    (1994) The kit ligand, Stem Cell Factor. Adv. Immunol 55, 1–96
    OpenUrlPubMedWeb of Science
    1. Godin I.,
    2. Dieterlen-Lievre F.,
    3. Cumano A.
    (1995). Emergence of multipotent hemopoietic cells in the yolk sac and paraaortic splanchnopleura in mouse embryos, beginning at 8.5 days postcoitus. Proc. Natl. Acad. Sci. U.S.A 92, 773–777
    OpenUrlAbstract/FREE Full Text
    1. Goodfellow P. J.,
    2. Wells S. A.
    (1995) Ret gene and its implications for cancer. J. Nat. Cancer Inst 87, 1515–1523
    OpenUrlAbstract/FREE Full Text
    1. Huizinga J. D.,
    2. Thuneberg L.,
    3. Kluppel M.,
    4. Malysz J.,
    5. Mikkelsen H. B.,
    6. Bernstein A.
    (1995) W /Kit gene required for interstitial cells of Cajal and for intestinal pacemaker activity. Nature 373, 347–349
    OpenUrlCrossRefPubMed
    1. Iwamoto T.,
    2. Takahashi M.,
    3. Ohbayashi M.,
    4. Nakashima I.
    (1992) The ret oncogene can induce melanogenesis and melanocyte development in Wv / Wv mice. Exp. Cell Res 200, 410–415
    OpenUrlCrossRefPubMedWeb of Science
    1. Keshet E.,
    2. Lyman S. D.,
    3. Williams D. E.,
    4. Anderson D. M.,
    5. Jenkins N. A.,
    6. Copeland N. G.,
    7. Parada L.F.
    (1991) Embryonic RNA expression patterns of the c- kit receptor and its cognate ligand suggest multiple functional roles in mouse development. EMBO J 10, 2425–2435
    OpenUrlPubMedWeb of Science
    1. Kitayama H.,
    2. Kanakura Y.,
    3. Furitsu T.,
    4. Tsujimura T.,
    5. Oritani K.,
    6. Ikeda H.,
    7. Sugahara H.,
    8. Mitsui H.,
    9. Kanayama Y.,
    10. Kitamura Y.,
    11. Matsuzawa Y.
    (1995) Constitutively activating mutations of c- kit receptor tyrosine kinase confer factor-independent growth and tumorigenicity of factor-dependent hematopoietic cell lines. Blood 85, 790–798
    OpenUrlAbstract/FREE Full Text
    1. Kress C.,
    2. Vogels R.,
    3. De Graaf W.,
    4. Bonnerot C.,
    5. Meijlink F.,
    6. Nicolas J.-F.,
    7. Deschamps J.
    (1990). Hox-2.3 upstream sequences mediate lacZ expression in intermediate mesoderm derivatives of transgenic mice. Development 109, 775–786
    OpenUrlAbstract/FREE Full Text
    1. Langton P.,
    2. Ward S. M.,
    3. Carl A.,
    4. Norell M. A.,
    5. Sanders K. M.
    (1989) Spontaneous electrical activity of interstitial cells of Cajal isolated from canine proximal colon. Proc. Natl. Acad. Sci. USA 86, 7280–7284
    OpenUrlAbstract/FREE Full Text
    1. Lecoin L.,
    2. Gabella G.,
    3. Le Douarin N.
    (1996) Origin of the c- kit -positive cells in the avian bowel. Development 122, 725–733
    OpenUrlAbstract
    1. Le Mouellic H.,
    2. Lallemand Y.,
    3. Brûlet P.
    (1990). Targeted replacement of the homeobox gene Hox-3.1 by the Escherichia coli lacZ in mouse chimeric embryons. Proc. Natl. Acad. Sci. USA 87, 4712–4716
    OpenUrlAbstract/FREE Full Text
    1. Manova K.,
    2. Nocka K.,
    3. Besmer P.,
    4. Bachvarova R. F.
    (1990) Gonadal expression of c- kit encoded at the W locus of the mouse. Development 110, 1057–1069
    OpenUrlAbstract/FREE Full Text
    1. Matsui Y.,
    2. Zsebo K. M.,
    3. Hogan B. L. M.
    (1990) Embryonic expression of a haematopoietic growth factor encoded by the Sl locus and the ligand for c- kit. Nature 347, 667–669
    OpenUrlCrossRefPubMed
    1. Mintz B.,
    2. Russell E. S.
    (1957) Gene-induced embryological modifications of primordial germ cells in the mouse. J. Exp. Zool 134, 207–237
    OpenUrlCrossRefPubMedWeb of Science
    1. Motro B.,
    2. Van der Koy B.,
    3. Rossant J.,
    4. Reith A.,
    5. Bernstein A.
    (1991) Contiguous patterns of c- kit and steel expression: analysis of mutations at the W and Sl loci. Development 113, 1207–1221
    OpenUrlAbstract
    1. Nocka K.,
    2. Tan J. C.,
    3. Chiu E.,
    4. Chu T. Y.,
    5. Ray P.,
    6. Trakman P.,
    7. Besmer P.
    (1990) Molecular bases of dominant-negative and loss of function mutations at the murine c- kit /white spotting locus: W37, WV, W41, and W. EMBO J 9, 1805–1813
    OpenUrlPubMedWeb of Science
    1. Ogawa M.,
    2. Matsuzaki Y.,
    3. Nishikawa S.,
    4. Hayashi S.-I.,
    5. Kunisada T.,
    6. Sudo T.,
    7. Kina T.,
    8. Nakauchi H.,
    9. Nishikawa S.-I.
    (1991) Expression and function of c- kit in hemopoietic progenitor cells. J.Exp.Med 174, 63–71
    OpenUrlAbstract/FREE Full Text
    1. Ogawa M.,
    2. Nishikawa S.,
    3. Yoshinaga K.,
    4. Hayashi S.-I.,
    5. Kunisada T.,
    6. Nakao J.,
    7. Kina T.,
    8. Sudo T.,
    9. Kodama H.,
    10. Nishikawa S.-I.
    (1993) Expression and function of c- kit in fetal hemopoietic progenitor cells: transition from the early c-kit-independent to the late c-kit-dependent wave of hemopoiesis in the murine embryo. Development 117, 1089–1098
    OpenUrlAbstract
    1. Orr-Urtreger A.,
    2. Avivi A.,
    3. Zimmer Y.,
    4. Givol D.,
    5. Yarden Y.,
    6. Lonai P.
    (1990) Developmental expression of c- kit, a proto-oncogene encoded by the W locus. Development 109, 911–923
    OpenUrlAbstract/FREE Full Text
    1. Pavan W. J.,
    2. Tilghman S. M.
    (1994) Piebald lethal (sl) acts early to disrupt the development of neural crest-derived melanocytes. Proc. Natl. Acad. Sci. USA 91, 7159–7163
    OpenUrlAbstract/FREE Full Text
    1. Reith A. D.,
    2. Rottapel R.,
    3. Giddens E.,
    4. Brady C.,
    5. Forrester L.,
    6. Bernstein A.
    (1990) W mutants mice with mild or severe developmental defects contain distinct point mutations in the kinase domain of the c- kit receptor. Genes Dev 4, 390–400
    OpenUrlAbstract/FREE Full Text
    1. Russell E. S.,
    2. Thompson M. W.,
    3. McFarland E. C.
    (1968) Analysis of effects of W and f genic substitutions on fetal mouse hematology. Genetics 58, 259–270
    OpenUrlFREE Full Text
    1. Sato T. N.,
    2. Towaza Y.,
    3. Deutsch U.,
    4. Wolburg-Buchlolz K.,
    5. Fujiwara Y.,
    6. Gendron-Maguire M.,
    7. Gridley T.,
    8. Wolburg H.,
    9. Risau W.,
    10. Qin Y.
    (1995) Distinct roles of the receptor tyrosine kinases Tie-1 and Tie-2 in blood vessel formation. Nature 376, 70–74
    OpenUrlCrossRefPubMed
    1. Shalaby F.,
    2. Rossant J.,
    3. Yamaguchi T. P.,
    4. Gertsenstein M.,
    5. Wu X.-F.,
    6. Breitman M. L.,
    7. Schuh A. C.
    (1995) Failure of blood-island formation and vasculogenesis in Flk-1-deficient mice. Nature 376, 62–66
    OpenUrlCrossRefPubMed
    1. Thuneberg L.
    (1982) Interstitial cells of Cajal: intestinal pacemakers?. Adv. Anat. Embryol. Cell Biol 71, 1–130
    OpenUrlPubMed
    1. Tsukamoto K.,
    2. Jackson I.,
    3. Hearing V.
    (1992) DOPAchrome tautomerase: identification of its gene and catalytic activity. EMBO J 11, 519–526
    OpenUrlPubMedWeb of Science
    1. Tsuzuki T.,
    2. Takahashi M.,
    3. Asai N.,
    4. Iwashita T.,
    5. Matsuyama M.,
    6. Asai J.
    (1995) Spatial and temporal expression of the ret proto-oncogene product in embryonic, infant and adult rat tissues. Oncogene 10, 191–198
    OpenUrlPubMedWeb of Science
    1. Weiss R. R.,
    2. Whitakermenezes D.,
    3. Longley J.,
    4. Bender J.,
    5. Murphy G. F.
    (1995) Human dermal endothelial cells express membrane-associated mast cell growth factor. J. Invest. Dermatol 104, 101–106
    OpenUrlCrossRefPubMedWeb of Science
    1. Witte O. N.
    (1990) Steel locus defines new multipotent growth factor. Cell 63, 5–6
    OpenUrlCrossRefPubMedWeb of Science
    1. Yamaguchi T. P.,
    2. Dumont D. J.,
    3. Conlon R. A.,
    4. Breitman M. L.,
    5. Rossant J.
    (1993) flk-1, an flt -related receptor tyrosine kinase is an early marker for endothelial cell precursors. Development 118, 489–498
    OpenUrlAbstract
    1. Young P. E.,
    2. Baumhueter S.,
    3. Lasky L. A.
    (1995) The sialomucin CD34 is expressed on hematopoietic cells and blood vessels during murine development. Blood 85, 96–105
    OpenUrlAbstract/FREE Full Text
    1. Zambrowicz B. P.,
    2. Zimmermann J. W.,
    3. Harendza C. J.,
    4. Simpson E. M.,
    5. Page D. C.,
    6. Brinster R. L.,
    7. Palmiter R. D.
    (1994) Expression of a mouse Zfy-1/lacZ transgene in the somatic cells of the embryonic gonad and germ cells of the adult testis. Development 120, 1549–1559
    OpenUrlAbstract
Back to top

 Download PDF

Email
JOURNAL ARTICLES
Spatial and temporal patterns of c-kit-expressing cells in WlacZ/+ and WlacZ/WlacZ mouse embryos
F. Bernex, P. De Sepulveda, C. Kress, C. Elbaz, C. Delouis, J.J. Panthier
Development 1996 122: 3023-3033;
del.icio.us logo Digg logo Reddit logo Twitter logo CiteULike logo Facebook logo Google logo Mendeley logo
Citation Tools
Alerts

Article navigation

Other journals from The Company of Biologists

Advertisement

Kathryn Virginia Anderson (1952-2020)

Developmental geneticist Kathryn Anderson passed away at home on 30 November 2020. Tamara Caspary, a former postdoc and friend, remembers Kathryn and her remarkable contribution to developmental biology.

Zooming into 2021

In a new Editorial, Editor-in-Chief James Briscoe and Executive Editor Katherine Brown reflect on the triumphs and tribulations of the last 12 months, and look towards a hopefully calmer and more predictable year.

Read & Publish participation extends worldwide

Over 60 institutions in 12 countries are now participating in our Read & Publish initiative. Here, James Briscoe explains what this means for his institution, The Francis Crick Institute. Find out more and view our full list of participating institutions.

Upcoming special issues

Imaging Development, Stem Cells and Regeneration
Submission deadline: 30 March 2021
Publication: mid-2021

The Immune System in Development and Regeneration
Guest editors: Florent Ginhoux and Paul Martin
Submission deadline: 1 September 2021
Publication: Spring 2022

Both special issues welcome Review articles as well as Research articles, and will be widely promoted online and at key global conferences.

Development presents...

Our successful webinar series continues into 2021, with early-career researchers presenting their papers and a chance to virtually network with the developmental biology community afterwards. Sign up to join our next session:

10 February
Time: 13:00 (GMT)
Chaired by: preLights