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Development 2011 Feb 01;1383:475-85. doi: 10.1242/dev.056010.
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Rapid differential transport of Nodal and Lefty on sulfated proteoglycan-rich extracellular matrix regulates left-right asymmetry in Xenopus.

Marjoram L , Wright C .

The spatiotemporally dynamic distribution of instructive ligands within embryonic tissue, and their feedback antagonists, including inherent stabilities and rates of clearance, are affected by interactions with cell surfaces or extracellular matrix (ECM). Nodal (here, Xnr1 or Nodal1 in Xenopus) and Lefty interact in a cross-regulatory relationship in mesendoderm induction, and are the conserved instructors of left-right (LR) asymmetry in early somitogenesis stage embryos. By expressing Xnr1 and Lefty proproteins that produce mature functional epitope-tagged ligands in vivo, we found that ECM is a principal surface of Nodal and Lefty accumulation. We detected Lefty moving faster than Nodal, with evidence that intact sulfated proteoglycans in the ECM facilitate the remarkable long distance movement of Nodal. We propose that Nodal autoregulation substantially aided by rapid ligand transport underlies the anteriorward shift of Nodal expression in the left LPM (lateral plate mesoderm), and speculate that the higher levels of chondroitin-sulfate proteoglycan (CSPG) in more mature anterior regions provide directional transport cues. Immunodetection and biochemical analysis showed transfer of Lefty from left LPM to right LPM, providing direct evidence that left-side-derived Lefty is a significant influence in ensuring the continued suppression of right-sided expression of Nodal, maintaining unilateral expression of this conserved determinant of asymmetry.

PubMed ID: 21205792
PMC ID: PMC3014634
Article link: Development
Grant support: [+]

Species referenced: Xenopus
Genes referenced: actl6a fn1 lefty myc nodal nodal1 sdc2 tjp1
Antibodies: Cdh1 Ab3 Cspg4 Ab1 Ctnnb1 Ab4 Fn1 Ab1 Itgb1 Ab1 Sdc2 Ab1

Article Images: [+] show captions
References [+] :
Aw, Is left-right asymmetry a form of planar cell polarity? 2009, Pubmed, Xenbase