TY - JOUR
T1 - Linking early determinants and cilia-driven leftward flow in left-right axis specification of Xenopus laevis
T2 - A theoretical approach
AU - Schweickert, Axel
AU - Walentek, Peter
AU - Thumberger, Thomas
AU - Danilchik, Mike
N1 - Funding Information:
We thank Martin Blum and Philipp Vick for valuable discussions and criticly reading of the manuscript and Susanne Bogusch for immunhistochemistry. TT and PW were recipients of Ph.D. fellowships from the Landesgraduiertenförderung Baden-Württemberg. Frog work in the Blum lab was funded by the Deutsche Forschungsgemeinschaft. MVD's research is supported by the National Science Foundation ( IOS-0921415 ).
PY - 2012/2
Y1 - 2012/2
N2 - In vertebrates, laterality - the asymmetric placement of the viscera including organs of the gastrointestinal system, heart and lungs - is under the genetic control of a conserved signaling pathway in the left lateral plate mesoderm (LPM). A key feature of this pathway, shared by embryos of all non-avian vertebrate classes analyzed to date (e.g. fish, amphibia and mammals) is the formation of a transitory midline epithelial structure. Remarkably, the motility of cilia projecting from this epithelium produce a leftward-directed movement of extracellular liquid. This leftward flow precedes any sign of asymmetry in gene expression. Numerous analyses have shown that this leftward flow is not only necessary, but indeed sufficient to direct laterality. Interestingly, however, cilia-independent mechanisms acting much earlier in development in the frog Xenopus have been reported during the earliest cleavage stages, a period before any major zygotic gene transcription. The relationship between these two distinct mechanisms is not understood. In this review we present the conserved and critical steps of Xenopus LR axis formation. Next, we address the basic question of how an early asymmetric activity might contribute to, feed into, or regulate the conserved cilia-dependent pathway. Finally, we discuss the possibility that Spemann's organizer is itself polarized in the left-right dimension. In attempting to reconcile the sufficiency of the cilia-dependent pathway with potential earlier-acting asymmetries, we offer a general practical experimental checklist for the Xenopus community working on the process of left-right determination. This approach indicates areas where work still needs to be done to clarify the relationship between early determinants and cilia-driven leftward flow.
AB - In vertebrates, laterality - the asymmetric placement of the viscera including organs of the gastrointestinal system, heart and lungs - is under the genetic control of a conserved signaling pathway in the left lateral plate mesoderm (LPM). A key feature of this pathway, shared by embryos of all non-avian vertebrate classes analyzed to date (e.g. fish, amphibia and mammals) is the formation of a transitory midline epithelial structure. Remarkably, the motility of cilia projecting from this epithelium produce a leftward-directed movement of extracellular liquid. This leftward flow precedes any sign of asymmetry in gene expression. Numerous analyses have shown that this leftward flow is not only necessary, but indeed sufficient to direct laterality. Interestingly, however, cilia-independent mechanisms acting much earlier in development in the frog Xenopus have been reported during the earliest cleavage stages, a period before any major zygotic gene transcription. The relationship between these two distinct mechanisms is not understood. In this review we present the conserved and critical steps of Xenopus LR axis formation. Next, we address the basic question of how an early asymmetric activity might contribute to, feed into, or regulate the conserved cilia-dependent pathway. Finally, we discuss the possibility that Spemann's organizer is itself polarized in the left-right dimension. In attempting to reconcile the sufficiency of the cilia-dependent pathway with potential earlier-acting asymmetries, we offer a general practical experimental checklist for the Xenopus community working on the process of left-right determination. This approach indicates areas where work still needs to be done to clarify the relationship between early determinants and cilia-driven leftward flow.
KW - Cilia
KW - Early determinants
KW - Ion-flux
KW - Left-right asymmetry
KW - Leftward flow
KW - Xenopus laevis
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UR - http://www.scopus.com/inward/citedby.url?scp=84856321241&partnerID=8YFLogxK
U2 - 10.1016/j.diff.2011.11.005
DO - 10.1016/j.diff.2011.11.005
M3 - Article
C2 - 22136958
AN - SCOPUS:84856321241
SN - 0301-4681
VL - 83
SP - S67-S77
JO - Differentiation
JF - Differentiation
IS - 2
ER -