Disease relevance of GDF1

• We show that heterozygous loss-of-function mutations in the human GDF1 gene contribute to cardiac defects ranging from tetralogy of Fallot to transposition of the great arteries and that decreased TGF- beta signaling provides a framework for understanding their pathogenesis [1].

High impact information on GDF1

• Growth/differentiation factor 1 (GDF-1) is a recently described member of the transforming growth factor beta superfamily isolated from a day-8.5 mouse embryo cDNA library [2].
• By immunohistochemical analysis, the protein encoded by the downstream open reading frame (GDF-1) was detected exclusively in the brain, spinal cord, and peripheral nerves in day-14.5 mouse embryos [2].
• The nucleotide sequence of GDF-1 predicts a protein of 357 amino acids with a mol wt of 38,600 [3].
• In vitro translation experiments were consistent with GDF-1 being a secreted glycoprotein [3].
• These results suggest that GDF-1 is most likely an extracellular factor mediating cell differentiation events during embryonic development [3].

Biological context of GDF1

• Growth/differentiation factor 1 (GDF1) is a transforming growth factor-beta family member that was originally isolated from an mouse embryo cDNA library [4].
• Cloning and sequence analysis revealed that this transcript contains two nonoverlapping open reading frames (ORFs), LASS1 and GDF1, which are quite different to the predicted sequences in GenBank (accession number XM_224734 and XM_224733) [4].
• Growth differentiation factor (GDF15) is a distant member of the transforming growth factor-beta superfamily, a diverse group of structurally related proteins that exert multiple effects on cell fate such as on cell growth and differentiation but little is known about GDF15 in these processes [5].

Anatomical context of GDF1

• These results indicate that GDF-1 and Nodal converge on ALK4 in the anterior primitive streak to control the formation of organizing centers that are necessary for normal forebrain and branchial arch development [6].
• Unlike that in the lateral plate mesoderm, Nodal expression in the node was independent of GDF-1, indicating that both factors act in parallel to control the development of mesendodermal precursors [6].
• The absence of these defects in single mutants indicated a synergistic interaction between Nodal and GDF-1 in the node, from which the axial mesendoderm that gives rise to the notochord, prechordal plate, and foregut endoderm originates, and where the two factors are co-expressed [6].
• Gdf1-/-;Nodal+/- mutants displayed several abnormalities that were not present in either Gdf1-/- or Nodal+/- single mutants, including absence of notochord and prechordal plate, and malformation of the foregut; organizing centers implicated in the development of the anterior head and branchial arches, respectively [6].

Other interactions of GDF1

• Expression of BMP-2, GDF-1, and PLAB could be modulated by treatment with differentiating agents [7].

References