Lefty (protein)

[2] Lefty, a divergent member of the transforming growth factor-β (TGF beta) superfamily of proteins, was originally discovered in the Hamada lab at the Osaka University using deletion screening of cDNA libraries in P19 embryonic carcinoma cells to find clones that did not differentiate when induced to differentiate using retinoic acid.

From these screens, researchers found one gene that was a tentative member of the TGF-beta superfamily that was predominantly expressed on the left side the embryo and aptly named it lefty.

Secreted lefty binds to EGF-CFC proteins like one-eyed pinhead in zebrafish keeping the essential cofactor from associating with NODAL/ Activin-like receptor complex.

Mutations in these genes cause incorrect positioning of these organs (e.g., situs inversus), or in the case of constitutively inactive lefty, the embryo becomes entirely mesoderm and fails to pattern or develop.

Lefty1 in the ventral midline prevents the Cerberus (paracrine factor or "Caronte") signal from passing to the right side of the embryo.

This mutation may cause congenital heart defects due to malformation, interrupted inferior vena cava, and lack of lung asymmetry (left pulmonary isomerism).

[8][9] Lefty-1 is a regulatory gene that plays a vital role in the determination of the left-right internal asymmetry observed in mammals.