tgfb 4

Left-right determination factor 2(LEFTY2) is a secreted protein which belongs to the TGF-beta family. Lefty was first identified in a screen for undifferentiated cell-specific cDNAs from the P19 mouse embryonal carcinoma cells. Its mRNA expression on the left side of the developing embryo earned the name “Lefty”. The human orthologue was initially identified as Ebaf, Endometrial bleeding associated factor. Lefty contains the six cysteine residues that are conserved among TGF-β related proteins and that are necessary to form the cysteineknot structure. Its function in patterning left-right asymmetry of the developing organ systems such as the heart and lung is consistent in all vertebrate species examined. Lefty acts as an antagonist to Nodal signaling, potentially by competing for binding to a common receptor. It may play a role in endometrial bleeding.

left-right determination factor 2 (Lefty2), also known as Left-right determination factor A (Lefty A), endometrial bleeding associated factor (left-right determination, factor A transforming growth factor-beta superfamily), and transforming growth factor beta-4, is a member of the TGF-beta family of proteins. This protein is secreted and plays a role in left-right asymmetry determination of organ systems during development. Lefty2/Lefty A may also play a role in endometrial bleeding. Mutations in Lefty2/Lefty A have been associated with left-right axis malformations, particularly in the heart and lungs. Some types of infertility have been associated with dysregulated expression of this gene in the endometrium. Alternative processing of this protein can yield three different products. Depletion of both Lefty1 and Lefty2 causes unchecked Nodal signaling, expansion of mesendoderm, and loss of ectoderm. The expansion of mesendoderm correlates with an extended period of rapid cellular internalization and a failure of deep-cell epiboly. The gastrulation defects of embryos depleted of Lefty1 and Lefty2 result from the deregulation of Squint signaling.