Jan L. Christian

Jan L. Christian, PhD

Languages spoken: English

Academic Information

Departments Primary - Neurobiology

Lab

Research Statement

Cell-cell signaling molecules such as bone morphogenetic proteins (BMPs) and nodals, play critical roles in specifying cell fate during vertebrate embryogenesis. Their activity must be strictly regulated to prevent birth defects, degenerative diseases and cancer. Our research program has two major foci:

1) Understanding how BMP activity is regulated by cleavage of the precursor protein and by interactions with the extracellular matrix. We use targeted mutagenesis in mice together with cell biological and biochemical approaches in Xenopus embryos to determine how cleavages within the inactive prodomain of the BMP precursor protein regulate the activity of mature BMP homodimers and heterodimers. We are also studying how point mutations within the prodomain of BMP4, which are associated with congenital birth defects in humans, impact BMP homodimer and heterodimer formation or function.

2) Analysis of signal transduction downstream of Tril. We discovered that the novel transmembrane protein Tril is required not only for blood formation but also for formation of the central nervous system, and that it does so by coordinately regulating nodal and BMP signaling in the embryo. In adults, Tril functions as a co-receptor for Toll-like receptors (Tlrs), which recognize foreign pathogens and mount an immune response. We are studying how this protein transduces signals from the membrane to the nucleus to control early development, and have discovered several new players in the signaling cascade activated by Tril in embryos.

Education History

Doctoral Training University of Washington School of Medicine
 PhD

Selected Publications

Journal Article

  1. Goldman DC, Berg LK, Heinrich MC, Christian J (2006). Ectodermally derived steel/stem cell factor functions non-cell autonomously during primitive erythropoiesis in Xenopus. Blood, 107(8), 3114-21.
  2. Goldman DC, Bailey AS, Pfaffle DL, Al Masri A, Christian JL, Fleming W (2009). BMP4 regulates the hematopoietic stem cell niche. Blood, 114(20), 4393-401.
  3. Goldman DC, Donley N, Christian J (2009). Genetic interaction between Bmp2 and Bmp4 reveals shared functions during multiple aspects of mouse organogenesis. Mechanisms of development, 126(3-4), 117-27.
  4. Degnin C, Jean F, Thomas G, Christian J (2004). Cleavages within the prodomain direct intracellular trafficking and degradation of mature bone morphogenetic protein-4. Molecular biology of the cell, 15(11), 5012-20.
  5. Kim HS, McKnite A, Xie Y, Christian J (2018). Fibronectin type III and intracellular domains of Toll-like receptor 4 interactor with leucine-rich repeats (Tril) are required for developmental signaling. Molecular biology of the cell, 29(5), 523-531.
  6. Kim HS, McKnite A, Christian J (2019). Proteolytic Activation of Bmps: Analysis of Cleavage in Xenopus Oocytes and Embryos. Methods in molecular biology (Clifton, N.J.), 1891, 115-133.
  7. Sokol S, Christian JL, Moon RT, Melton D (1991). Injected Wnt RNA induces a complete body axis in Xenopus embryos. Cell, 67(4), 741-52.
  8. Cui Y, Tian Q, Christian J (1996). Synergistic effects of Vg1 and Wnt signals in the specification of dorsal mesoderm and endoderm. Developmental biology, 180(1), 22-34.
  9. Sopory S, Kwon S, Wehrli M, Christian J (2010). Regulation of Dpp activity by tissue-specific cleavage of an upstream site within the prodomain. Developmental biology, 346(1), 102-12.
  10. Dalgin G, Goldman DC, Donley N, Ahmed R, Eide CA, Christian J (2007). GATA-2 functions downstream of BMPs and CaM KIV in ectodermal cells during primitive hematopoiesis. Developmental biology, 310(2), 454-69.
  11. Mimoto, M.S., Kwon, S., Green, Y.S., Goldman, D., and Christian, J.L (2015). GATA2 regulates Wnt signaling to promote primitive red blood cell fate. Developmental biology, 407, 1-11.
  12. Mimoto MS, Kwon S, Green YS, Goldman D, Christian J (2015). GATA2 regulates Wnt signaling to promote primitive red blood cell fate. Developmental biology, 407(1), 1-11.
  13. Christian JL, McMahon JA, McMahon AP, Moon R (1991). Xwnt-8, a Xenopus Wnt-1/int-1-related gene responsive to mesoderm-inducing growth factors, may play a role in ventral mesodermal patterning during embryogenesis. Development (Cambridge, England), 111(4), 1045-55.
  14. Nakayama T, Snyder MA, Grewal SS, Tsuneizumi K, Tabata T, Christian J (1998). Xenopus Smad8 acts downstream of BMP-4 to modulate its activity during vertebrate embryonic patterning. Development (Cambridge, England), 125(5), 857-67.
  15. Walters MJ, Wayman GA, Notis JC, Goodman RH, Soderling TR, Christian J (2002). Calmodulin-dependent protein kinase IV mediated antagonism of BMP signaling regulates lineage and survival of hematopoietic progenitors. Development (Cambridge, England), 129(6), 1455-66.
  16. Birsoy B, Berg L, Williams PH, Smith JC, Wylie CC, Christian JL, Heasman (2005). XPACE4 is a localized pro-protein convertase required for mesoderm induction and the cleavage of specific TGFbeta proteins in Xenopus development. Development (Cambridge, England), 132(3), 591-602.
  17. Goldman DC, Hackenmiller R, Nakayama T, Sopory S, Wong C, Kulessa H, Christian J (2006). Mutation of an upstream cleavage site in the BMP4 prodomain leads to tissue-specific loss of activity. Development (Cambridge, England), 133(10), 1933-42.
  18. Green, Y.S., Mimoto, M.S., Kwon, S., Xi, Y. and Christian, J. (2016). Tril targets Smad7 for degradation to allow for hematopoietic specification in Xenopus embryos. Development (Cambridge, England), 143, 4016-4026.
  19. Tilak A, Nelsen SM, Kim HS, Donley N, McKnite A, Lee H, Christian J (2014). Simultaneous rather than ordered cleavage of two sites within the BMP4 prodomain leads to loss of ligand in mice. Development (Cambridge, England), 141(15), 3062-71.
  20. Christian JL, Olson DJ, Moon R (1992). Xwnt-8 modifies the character of mesoderm induced by bFGF in isolated Xenopus ectoderm. The EMBO journal, 11(1), 33-41.
  21. Cui Y, Jean F, Thomas G, Christian J (1998). BMP-4 is proteolytically activated by furin and/or PC6 during vertebrate embryonic development. The EMBO journal, 17(16), 4735-43.
  22. Christian JL, Moon R (1993). Interactions between Xwnt-8 and Spemann organizer signaling pathways generate dorsoventral pattern in the embryonic mesoderm of Xenopus. Genes & development, 7(1), 13-28.
  23. Cui Y, Hackenmiller R, Berg L, Jean F, Nakayama T, Thomas G, Christian J (2001). The activity and signaling range of mature BMP-4 is regulated by sequential cleavage at two sites within the prodomain of the precursor. Genes & development, 15(21), 2797-802.
  24. Nelsen SM, Christian J (2009). Site-specific cleavage of BMP4 by furin, PC6, and PC7. The Journal of biological chemistry, 284(40), 27157-66.
  25. Kwon S, Christian J (2011). Sortilin associates with transforming growth factor-beta family proteins to enhance lysosome-mediated degradation. The Journal of biological chemistry, 286(24), 21876-85.
  26. Sopory S, Nelsen S, Degnin C, Wong C, Christian J (2006). Regulation of BMP-4 protein by sequence elements within the prodomain. The Journal of biological chemistry, 281, 34021-34031.
  27. Wayman GA, Walters MJ, Kolibaba K, Soderling TR, Christian J (2000). CaM kinase IV regulates lineage commitment and survival of erythroid progenitors in a non-cell-autonomous manner. The Journal of cell biology, 151(4), 811-24.
  28. Tsuneizumi K, Nakayama T, Kamoshida Y, Kornberg TB, Christian JL, Tabata (1997). Daughters against dpp modulates dpp organizing activity in Drosophila wing development. Nature, 389(6651), 627-31.
  29. Nakao A, Afrakhte M, Moren A, Nakayama T, Christian JL, Heuchel R, Itoh S, Kawabata M, Heldin NE, Heldin CH, ten Dijke (1997). Identification of Smad7, a TGFbeta-inducible antagonist of TGF-beta signalling. Nature, 389(6651), 631-5.
  30. Neugebauer JM, Kwon S, Kim HS, Donley N, Tilak A, Sopory S, Christian J (2015). The prodomain of BMP4 is necessary and sufficient to generate stable BMP4/7 heterodimers with enhanced bioactivity in vivo. Proceedings of the National Academy of Sciences of the United States of America, 112(18), E2307-16.
  31. Kim HS, Green YS, Xie Y, Christian J (2021). Tril dampens Nodal signaling through Pellino2- and Traf6-mediated activation of Nedd4l. Proceedings of the National Academy of Sciences of the United States of America, 118(36),
  32. Olson DJ, Christian JL, Moon R (1991). Effect of wnt-1 and related proteins on gap junctional communication in Xenopus embryos. Science (New York, N.Y.), 252(5009), 1173-6.
  33. Mimoto M, Christian J (2012). Friend of GATA (FOG) Interacts with the Nucleosome Remodeling and Deacetylase Complex (NuRD) to Support Primitive Erythropoiesis in Xenopus laevis. PloS one, 7(1), e29882.
  34. Kim HS, Christian J (2021). Analysis of Transforming Growth Factor ß Family Cleavage Products Secreted Into the Blastocoele of Xenopus laevis Embryos. Journal of visualized experiments, (173),
  35. Christian J (2012). Morphogen gradients in development: from form to function. Wiley interdisciplinary reviews. Developmental biology, 1(1), 3-15.
  36. Kim HS, Neugebauer J, McKnite A, Tilak A, Christian J (2019). BMP7 functions predominantly as a heterodimer with BMP2 or BMP4 during mammalian embryogenesis. eLife, 8,

Review

  1. Moon RT, Christian J (1992). Competence modifiers synergize with growth factors during mesoderm induction and patterning in Xenopus. Cell, 71(5), 709-12.
  2. Christian J (2012). Morphogen gradients in development: from form to function. Wiley interdisciplinary reviews. Developmental biology, 1, 3-15.

Book Chapter

  1. Goldman D, Christian J (2004). Cell Signaling during early hematopoietic development. 429-450.
  2. Sopory S, Christian J (2006). Regulation of TGF-ß family activity by proprotein processing. 37-60.

Conference Proceedings

  1. Christian JL, Heldin C (2017). The TGFβ superfamily in Lisbon: navigating through development and disease. Development (Cambridge, England), 144(24), 4476-4480.

Editorial

  1. Christian JL, Hill C (2022). Transforming growth factor-ß family biology: From basic mechanisms to roles in development and disease. Developmental dynamics, 251(1), 6-9.