- NODAL
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Nodal is a protein that in humans is encoded by the NODAL gene.[1][2] It is a member of the TGF beta superfamily. Like many other members of this superfamily, it is involved in cell differentiation. Studies of the mouse counterpart suggested that this gene may be essential for mesoderm formation and subsequent organization of left-right axial structures in early embryonic development.[2]
Contents
Function
The left-right asymmetry in the body of vertebrates is established by a process that uses the Nodal and Lefty proteins; Nodal is expressed in the left side of the organism in early development.[3] An ortholog of Nodal was recently found in snails and was shown to be involved in left-right asymmetry as well.[4]
Nodal signaling is important very early in development for cell fate determination and for many other developmental processes.[5] A nodal knockout in mouse causes the absence of the primitive streak and failure in the formation of mesoderm, leading to developmental arrest just after gastrulation.[6][7][8]
Nodal is widely distributed cytokine.[9] The presence of Nodal is not only limited to vertebrates, it is also known to be conserved in other chordates, deuterostomes (cephalochordates, tunicates and echinoderms) and protostomes such as snails, but interestingly neither the nematode C. elegans (another protosome) nor the fruit fly (an arthropode) have a copy of nodal.[10][11] Although mouse and human only have one nodal gene, the zebra fish contain three nodal paralogs: squint , cyclops and southpaw, and the frog five (xnr1,2,3,5 and 6). Even though the zebra fish Nodal homologs are very similar, they have specialized to perform different roles; for instance, Squint and Cyclops are important for mesoendoderm formation, whereas to Southpaw that has a major role in asymmetric heart morphogenesis and visceral left-right asymmetry.[12] Another example of protein speciation is the case of the frog where Xnr1 and Xnr2 regulate movements in gastrulation in contrast to Xnr5 and Xnr6 that are involved in mesoderm induction.[13] Mouse Nodal has been implicated in left-right asymmetry, neural pattering and mesoderm induction (see nodal signaling).
References
- ^ Gebbia M, Ferrero GB, Pilia G, Bassi MT, Aylsworth A, Penman-Splitt M, Bird LM, Bamforth JS, Burn J, Schlessinger D, Nelson DL, Casey B (Dec 1997). "X-linked situs abnormalities result from mutations in ZIC3". Nat Genet 17 (3): 305–8. doi:10.1038/ng1197-305. PMID 9354794.
- ^ a b "Entrez Gene: NODAL nodal homolog (mouse)". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=4838.
- ^ Hamada H, Meno C, Watanabe D, Saijoh Y (February 2002). "Establishment of vertebrate left-right asymmetry". Nat. Rev. Genet. 3 (2): 103–13. doi:10.1038/nrg732. PMID 11836504.
- ^ Grande C, Patel NH (February 2009). "Nodal signalling is involved in left-right asymmetry in snails". Nature 457 (7232): 1007–11. doi:10.1038/nature07603. PMC 2661027. PMID 19098895. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2661027.
- ^ Dougan ST, Warga RM, Kane DA, Schier AF, Talbot WS (May 2003). "The role of the zebrafish nodal-related genes squint and cyclops in patterning of mesendoderm". Development 130 (9): 1837–51. PMID 12642489.
- ^ Conlon FL, Lyons KM, Takaesu N, Barth KS, Kispert A, Herrmann B, Robertson EJ (July 1994). "A primary requirement for nodal in the formation and maintenance of the primitive streak in the mouse". Development 120 (7): 1919–28. PMID 7924997.
- ^ Zhou X, Sasaki H, Lowe L, Hogan BL, Kuehn MR (February 1993). "Nodal is a novel TGF-beta-like gene expressed in the mouse node during gastrulation". Nature 361 (6412): 543–7. doi:10.1038/361543a0. PMID 8429908.
- ^ Reissmann E, Jörnvall H, Blokzijl A, et al. (August 2001). "The orphan receptor ALK7 and the Activin receptor ALK4 mediate signaling by Nodal proteins during vertebrate development". Genes Dev. 15 (15): 2010–22. doi:10.1101/gad.201801. PMC 312747. PMID 11485994. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=312747.
- ^ Chen, Hsu-Hsin & Geijsen, Neils (2006). "Signaling germline commitment". In Simón, Carlos & Pellicer, Antonio. Stem cells in human reproduction: basic science and therapeutic potential. CRC Press. p. 74. ISBN 9780415397773. http://books.google.com/books?id=rShYiEGhvt4C&pg=PA74.
- ^ Chea HK, Wright CV, Swalla BJ (October 2005). "Nodal signaling and the evolution of deuterostome gastrulation". Dev. Dyn. 234 (2): 269–78. doi:10.1002/dvdy.20549. PMID 16127715.
- ^ Schier AF (November 2009). "Nodal morphogens". Cold Spring Harb Perspect Biol 1 (5): a003459. doi:10.1101/cshperspect.a003459. PMC 2773646. PMID 20066122. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2773646.
- ^ Baker K, Holtzman NG, Burdine RD (September 2008). "Direct and indirect roles for Nodal signaling in two axis conversions during asymmetric morphogenesis of the zebrafish heart". Proc. Natl. Acad. Sci. U.S.A. 105 (37): 13924–9. doi:10.1073/pnas.0802159105. PMC 2544555. PMID 18784369. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2544555.
- ^ Luxardi G, Marchal L, Thomé V, Kodjabachian L (February 2010). "Distinct Xenopus Nodal ligands sequentially induce mesendoderm and control gastrulation movements in parallel to the Wnt/PCP pathway". Development 137 (3): 417–26. doi:10.1242/dev.039735. PMID 20056679.
Further reading
- Postovit LM, Seftor EA, Seftor RE, Hendrix MJ (2007). "Targeting Nodal in malignant melanoma cells.". Expert Opin. Ther. Targets 11 (4): 497–505. doi:10.1517/14728222.11.4.497. PMID 17373879.
- Yan YT, Liu JJ, Luo Y, et al. (2002). "Dual roles of Cripto as a ligand and coreceptor in the nodal signaling pathway.". Mol. Cell. Biol. 22 (13): 4439–49. doi:10.1128/MCB.22.13.4439-4449.2002. PMC 133918. PMID 12052855. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=133918.
- Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences.". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=139241.
- Roberts HJ, Hu S, Qiu Q, et al. (2003). "Identification of novel isoforms of activin receptor-like kinase 7 (ALK7) generated by alternative splicing and expression of ALK7 and its ligand, Nodal, in human placenta.". Biol. Reprod. 68 (5): 1719–26. doi:10.1095/biolreprod.102.013045. PMID 12606401.
- Munir S, Xu G, Wu Y, et al. (2004). "Nodal and ALK7 inhibit proliferation and induce apoptosis in human trophoblast cells.". J. Biol. Chem. 279 (30): 31277–86. doi:10.1074/jbc.M400641200. PMID 15150278.
- Haffner C, Frauli M, Topp S, et al. (2005). "Nicalin and its binding partner Nomo are novel Nodal signaling antagonists.". Embo J. 23 (15): 3041–50. doi:10.1038/sj.emboj.7600307. PMC 514924. PMID 15257293. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=514924.
- Besser D (2004). "Expression of nodal, lefty-a, and lefty-B in undifferentiated human embryonic stem cells requires activation of Smad2/3.". J. Biol. Chem. 279 (43): 45076–84. doi:10.1074/jbc.M404979200. PMID 15308665.
- Bamforth SD, Bragança J, Farthing CR, et al. (2004). "Cited2 controls left-right patterning and heart development through a Nodal-Pitx2c pathway.". Nat. Genet. 36 (11): 1189–96. doi:10.1038/ng1446. PMID 15475956.
- Gerhard DS, Wagner L, Feingold EA, et al. (2004). "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).". Genome Res. 14 (10B): 2121–7. doi:10.1101/gr.2596504. PMC 528928. PMID 15489334. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=528928.
- Vallier L, Reynolds D, Pedersen RA (2005). "Nodal inhibits differentiation of human embryonic stem cells along the neuroectodermal default pathway.". Dev. Biol. 275 (2): 403–21. doi:10.1016/j.ydbio.2004.08.031. PMID 15501227.
- Hart AH, Willson TA, Wong M, et al. (2005). "Transcriptional regulation of the homeobox gene Mixl1 by TGF-beta and FoxH1.". Biochem. Biophys. Res. Commun. 333 (4): 1361–9. doi:10.1016/j.bbrc.2005.06.044. PMID 15982639.
- Vallier L, Alexander M, Pedersen RA (2006). "Activin/Nodal and FGF pathways cooperate to maintain pluripotency of human embryonic stem cells.". J. Cell. Sci. 118 (Pt 19): 4495–509. doi:10.1242/jcs.02553. PMID 16179608.
External links
Cell signaling: TGF beta signaling pathway TGF beta superfamily of ligands TGF beta family (TGF-β1, TGF-β2, TGF-β3)
Bone morphogenetic proteins (BMP2, BMP3, BMP4, BMP5, BMP6, BMP7, BMP8a, BMP8b, BMP10 , BMP15)
Growth differentiation factors (GDF1, GDF2, GDF3, GDF5, GDF6, GDF7, Myostatin/GDF8, GDF9, GDF10, GDF11, GDF15)
Other (Activin and inhibin, Anti-müllerian hormone, Nodal)TGF beta receptors
(Activin, BMP)TGFBR1: Activin type 1 receptors (ACVR1, ACVR1B, ACVR1C) · ACVRL1 · BMPR1 (BMPR1A · BMPR1B)
TGFBR2: Activin type 2 receptors (ACVR2A, ACVR2B) · AMHR2 · BMPR2
TGFBR3: betaglycanTransducers/SMAD Ligand inhibitors Coreceptors Other SARAB trdu: iter (nrpl/grfl/cytl/horl), csrc (lgic, enzr, gprc, igsr, intg, nrpr/grfr/cytr), itra (adap, gbpr, mapk), calc, lipd; path (hedp, wntp, tgfp+mapp, notp, jakp, fsap, hipp, tlrp) Categories:- Human proteins
- Developmental genes and proteins
- TGFβ domain
- Chromosome 10 gene stubs
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