Brief reviewsLeft-Right Determination☆
Section snippets
Organizing Structures
The term node defines the mammalian structure that is homologous to Hensen's node in avians and Spemann's organizer in amphibians. This homology includes its embryological origin, its ability to induce axial specification of the body plan and its profile of gene expression Beddington 1994, Izpisua-Belmonte et al. 1993. Recent reports support a key role for the node in the initial specification of the left and right sides of the body. In chick, morphological asymmetry of Hensen's node is the
Signals to Organ Primordia
The earliest molecular asymmetries in the mouse occur after the establishment of nodal flow with the appearance of the TGF-β superfamily members nodal and Lefty-1 on the left side adjacent to the node Lowe et al. 1996, Meno et al. 1996. Aberrant patterns of nodal expression correlate with situs abnormalities and missexpression of nodal on the right side of the embryo results in randomized situs Levin et al. 1995, Lohr et al. 1997, Lowe et al. 1996, Ryan et al. 1998. In the chick, nodal
Human Genetics of Laterality
Autosomal dominant, autosomal recessive, and X-linked inheritance patterns have been described for syndromic human situs abnormalities. However, our knowledge of these defects is largely limited to the clinical evaluation of familial cases. Several known genes in the L/R signaling cascade have been cloned in humans, often as a result of mapping candidate genes for diverse syndromes.
Kartagener's syndrome is an inherited disease characterized by the clinical triad of bronchiectasis, sinusitis,
Conclusion
In the last years significant progress has been made in terms of identifying the individual molecular components necessary for determining left-right patterning decisions and their position within the signaling cascade hierarchy. In chick, an activin or activin-related molecule appears to be critical for initiation of asymmetric gene expression in the vicinity of the node. In mice, “nodal flow” breaks the initial bilateral symmetry and signals the onset of a molecular cascade of asymmetric gene
Acknowledgements
We thank Dr. Brian Cooper for critical reading of the manuscript. P.R.-L. is a recipient of AHA Western States Affiliate Beginning Grant-in-Aid. A.K.R. is a recipient of the Burroughs Wellcome Fund Career Award.
References (56)
- et al.
Developmental genetics of the heart
Curr Opin Genet Dev
(1996) - et al.
Drosophila midgut morphogenesis requires the function of the segmentation gene odd-paired
Dev Biol
(1995) - et al.
A cascade of gene action controlling heart asymmetry and torsion in embryonic development
Trends Cardiovasc Med
(1998) Links in the left/right axial pathway
Cell
(1998)- et al.
The homeobox gene goosecoid and the origin of organizer cells in the early chick blastoderm
Cell
(1993) - et al.
Characterization and mutation analysis of human LEFTY A and LEFTY B, homologues of murine genes implicated in left-right axis development
Am. J Hum Genet
(1999) - et al.
Left-right developmentmammalian phenotypes and conceptual models
Cell Dev Biol
(1998) - et al.
A molecular pathway determining left-right asymmetry in chick embryogenesis
Cell
(1995) - et al.
Left/right patterning signals and the independent regulation of difference aspects of situs in the chick embryo
Dev Biol
(1997) - et al.
The transcription factor Pitx2 mediates situs-specific morphogenesis in response to left-right asymmetric signals
Cell
(1998)
lefty-1 is required for left-right determination as a regular of lefty-2 and nodal
Cell
Randomization of left-right asymmetry due to loss of nodal cilia generating leftward flow of extraembryonic fluid in mice lacking KIF3B motor protein
Cell
Abnormal nodal flow precedes situs inversus in iv and inv mice
Mol Cell
Pitx2 participates in the late phase of the pathway controlling left-right asymmetry
Cell
Antagonistic signaling by Caronte, a novel Cerberus-related gene, establishes left-right asymmetric gene expression
Cell
Pitx2, a bicoid-type homeobox gene, is involved in a lefty-signaling pathway in determination of left-right asymmetry
Cell
Induction of a second neural axis by the mouse node
Development
Identification of Sonic hedgehog as a candidate gene responsible for holoprosencephaly
Nat Genet
Odd-paireda zinc finger pair-rule protein required for the timely activation of engrailed and wingless in Drosophila embryos
Genes Dev
Smad5 knockout mice die at mid-gestation due to multiple embryonic and extraembryonic defects
Development
Retinoic acid is required in the mouse embryo for left-right asymmetry determination and heart morphogenesis
Development
Mutation of the mouse hepatocyte nuclear factor/forkhead homologue 4 gene results in an absence of cilia and random left-right asymmetry
J Clin Invest
A primary requirement for nodal in the formation and maintenance of the primitive streak in the mouse
Development
Vertebrate embryo handedness
Nature
Dosage requirement of Pitx2 for development of multiple organs
Development
X-linked situs abnormalities result from mutations in ZIC3
Nat Genet
Immotilie cilia syndrome including polysplenia, situs inversus, and extrahepatic biliary artesia
Am J Med Genet
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2009, The Dopaminergic Mind in Human Evolution and History
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