Regulation of midline development by antagonism of lefty and nodal signaling.
The embryonic midline is crucial for the development of embryonic pattern including bilateral symmetry and left-right asymmetry. In zebrafish, lefty1 (lft1) and lefty2 (lft2) have distinct midline expression domains along the anteroposterior axis that overlap with the expression patterns of the nodal-related genes cyclops and squint. Altered expression patterns of lft1 and lft2 in zebrafish mutants that affect midline development suggests different upstream pathways regulate each expression domain. Ectopic expression analysis demonstrates that a balance of lefty and cyclops signaling is required for normal mesendoderm patterning and goosecoid, no tail and pitx2 expression. In late somite-stage embryos, lft1 and lft2 are expressed asymmetrically in the left diencephalon and left lateral plate respectively, suggesting an additional role in laterality development. A model is proposed by which the vertebrate midline, and thus bilateral symmetry, is established and maintained by antagonistic interactions among co-expressed members of the lefty and nodal subfamilies of TGF-beta signaling molecules.
Bisgrove
B W
BW
Huntsman Cancer Institute, Center for Children, University of Utah, Salt Lake City, UT 84112, USA.
Essner
J J
JJ
Yost
H J
HJ
D000595:Amino Acid Sequence; D000818:Animals; D019521:Body Patterning / Q000235:genetics*; D004625:Embryo, Nonmammalian; D004627:Embryonic Induction / Q000235:genetics; D004707:Endoderm / Q000378:metabolism; D005775:Gastrula; D018507:Gene Expression Regulation, Developmental; D047908:Intracellular Signaling Peptides and Proteins; D055458:Left-Right Determination Factors; D008648:Mesoderm / Q000378:metabolism; D008969:Molecular Sequence Data; D009154:Mutation; D055457:Nodal Protein; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism*; D015027:Zebrafish / Q000196:embryology*; D029961:Zebrafish Proteins
D047908:Intracellular Signaling Peptides and Proteins; D055458:Left-Right Determination Factors; D055457:Nodal Protein; D016212:Transforming Growth Factor beta; D029961:Zebrafish Proteins; C512832:ndr2 protein, zebrafish