Publication: A loss-of-function mutation in the CFC domain of TDGF1 is associated with human forebrain defects
Loading...
Official URL
Full text at PDC
Publication Date
2002-05
Advisors (or tutors)
Editors
Journal Title
Journal ISSN
Volume Title
Publisher
Springer-Verlag
Citations
Exportar
Abstract
TDGF1 (CRIPTO) is an EGF-CFC family member and an obligate co-receptor involved in NODAL signaling, a developmental program implicated in midline, forebrain, and left-right axis development in model organisms. Previous studies of CFC1 (CRYPTIC), another member of the EGF-CFC family, demonstrated that normal function of this protein is required for proper laterality development in humans. Here we identify a mutation in the conserved CFC domain of TDGF1 in a patient with midtine anomalies of the forebrain. The mutant protein is inactive in a zebrafish rescue assay, indicating a role for TDGF1 in human midline and forebrain development.
Description
© Springer-Verlag 2002.
We sincerely thank j.D. Karkera for assistence with protein prediction algorithms, W.B. Dobyns for reading the brain scans of the patients. R.D.B. is supported by a Cancer Research Fund Fellowship of the Damon Runyon-Walter Winchell Foundation. A.F.S. is a Scholar of the McKnight Endowment Fund for Neuroscience and the Irma T. Hirschl Trust. This work is supported by grants from the NIH (A.F.S.) and by the Division of Intramural Research, NHGRI, NIH (M.M.).
UCM subjects
Unesco subjects
Keywords
Citation
Bamford RN, Roessler E, Burdine RD, Saplakoglu U, dela Cruz J, Splitt M, Towbin J, et al (2000) Loss-of-function mutations in the EGF-CFC gene CFC1 are associated with human left-right laterality defects. Nat Genet 26:365–369
Burdine RD, Schier AF (2000) Conserved and divergent mechanisms in left-right axis formation. Genes Dev 14:763–776
Conlon FL, Lyons KM, Takaesu N, Barth KS, Kispert A, Herrmann B, Robertson EJ (1994) A primary requirement for nodal in the formation and maintenance of the primitive streak in the mouse. Development 120:1919–1928
den Dunnen JT, Antonarakis SE (2001) Nomenclature for the description of human sequence variations. Hum Genet 109:121–124
Ding J, Yang L, Yan Y-T, Chen A, Desai N, Wynshaw-Boris A, Shen MM (1998) Cripto is required for correct orientation of the anterior-posterior axis in the mouse embryo. Nature 395: 702–707
Feldman B, Gates MA, Egan ES, Dougan ST, Rennebeck G, Sirotkin HI, Schier AF, et al (1998) Zebrafish organizer development and germ-layer formation require nodal-related signals. Nature 395:181–185
Gritsman K, Zhang J, Cheng S, Heckscher E, Talbot WS, Schier AF (1999) The EGF-CFC Protein One-Eyed Pinhead Is Essential for Nodal Signaling. Cell 97:121–132
Gritsman K, Talbot WS, Schier AF (2000) Nodal signaling patterns the organizer. Development 127:921–932
Minchiotti G, Parisi S, Liguori G, Signore M, Lania G, Adamson ED, Lago CT, et al. (2000) Membrane Anchorage of Cripto protein by glycosylphosphatidlyinositiol and its distribution during early mouse development. Mech Dev 90:133–142
Muenke M, Beachy P (2001) Holoprosencephaly. In: Scriver CR, Beaudet AL, Sly WS, Valle D, Childs B, Kinzler KW, Vogelstein B (eds) The metabolic and molecular bases of inherited disease. 250: Holoprosencephaly. McGraw-Hill, pp 6203–6230
Nanni L, Ming JE, Bocian M, Steinhaus K, Bianchi DW, Die-Smulders C, Giannotti A, Imaizumi K, Jones KL, Campo MD, Martin RA, Meinecke P, Pierpont ME, Robin NH, Young ID, Roessler E, Muenke M (1999) The mutational spectrum of the Sonic Hedgehog gene in holoprosencephaly: SHH mutations cause a significant proportion of autosomal dominant holoprosencephaly. Hum Mol Genet 8:2479–88
Povey S, Lovering R, Bruford E, Wright M, Lush M, Wain (2001) The HUGO Gene Nomenclature Committee (HGNC). Hum Genet DOI 10.1007/s00439-001-0615-0
Roessler E, Muenke M (2001) Midline and laterality defects: left and right meet in the middle. Bioessays 23:888–900
Schier AF, Shen MM (2000) Nodal signalling in vertebrate development. Nature 403:385–389
Schier AF, Talbot WS (2001) Nodal signaling and the zebrafish organizer. Int J Dev Biol 45:289–297
Schier AF, Neuhauss SCF, Helde KA, Talbot WS, Driever W (1997) The one-eyed pinhead gene functions in mesoderm and endoderm formation in zebrafish and interacts with no tail. Development 124:327–342
Shen MM, Schier AF (2000) The EGF-CFC gene family in vertebrate development. Trends Genet 16: 303–309
Shen MM, Wang H, Leder P (1997) A differential display strategy identifies Cryptic, a novel EGF-related gene expressed in the axial and lateral mesoderm during mouse gastrulation. Development 124:429–442
Strahle U, Jesuthasan S, Blader P, Garcia-Villalba P, Hatta K, Ingham PW (1997) one-eyed pinhead is required for development of the ventral midline of the zebrafish (Danio rerio) neural tube. Genes Funct 1:131–148
Yan, Y-T, Gritsman K, Ding J, Burdine RD, Corrales JD, Price SM, Talbot WS, et al (1999) Conserved requirement for EGF-CFC genes in vertebrate left-right axis formation. Genes Dev 13: 2527–2537
Yeo C-Y, Whitman M (2001) Nodal signals to Smads through Cripto-Dependent and Cripto-independent mechanisms. Mol Cell 7:949–957
Zhang J, Talbot WS, Schier AF (1998) Positional cloning identifies zebrafish one-eyed pinhead as a permissive EGF-related ligand required during gastrulation. Cell 92:241–251
Zhou X, Sasaki H, Lowe L, Hogan BL, Kuehn MR (1993) Nodal is a novel TGF-beta-like gene expressed in the mouse node during gastrulation. Nature 361:543–547