 |
Left/Right axis formation decisions are made very early in development, when the primitive streak first forms on the nearly symmetrical embryo disc, and continue through embryogenesis. Recently the formation of the left/right axis has opened up with the discovery of mechanisms that are involved in establishing this axis. Intriguingly, while so many of our signaling mechanisms have been evolutionarily conserved, some species appear to regulate this L/R axis differently. |
Hensen's node |
The left/right axis appears at first mirror symetrical, and looks very similar externally, but clearly many internal organs are not duplicated (heart, liver, brain etc). Each particular axis of the embryo appears to be independently established using a number of different developmental mechanisms.
While early axis events are difficult
to track, later internal changes occur on
a large scale. In some cases there is a
loss of an initial symetrical L/R
structure, the most obvious of these is
the remodelling of the cardiac outflow,
involving regression and loss of arch
arteries etc.
Page Links: Introduction | Some Recent Findings | References |
Related Pages: Factors - Nodal | Early Axes | rostro/caudal | anterior/posterior | Limb |
Garic-Stankovic A, Hernandez M, Flentke GR, Zile MH, Smith SM. A ryanodine receptor-dependent Cai2+ asymmetry at Hensen's node mediates avian lateral identity. Development. 2008 Oct;135(19):3271-80.
"In mouse, the establishment of left-right (LR) asymmetry requires intracellular calcium (Ca(i)(2+)) enrichment on the left of the node. We report here that the avian embryo uses a left-side enriched Ca(i)(2+) asymmetry across Hensen's node to govern its lateral identity."
Baker K, Holtzman NG, Burdine RD. Direct and indirect roles for Nodal signaling in two axis conversions during asymmetric morphogenesis of the zebrafish heart. Proc Natl Acad Sci U S A. 2008 Sep 16;105(37):13924-9. (More? Factors - Nodal)
"The Nodal signaling pathway plays a conserved role in determining left-sided identity in vertebrates with this early left-right (L/R) patterning influencing the asymmetric development and placement of visceral organs. ...These results suggest that Nodal signaling directs asymmetric cardiac morphogenesis through establishing and subsequently reinforcing laterality information over the course of cardiac development."
Wardle FC, Papaioannou VE. Teasing out T-box targets in early mesoderm. Curr Opin Genet Dev. 2008 Sep 5.
"T-box transcription factor genes are widely conserved in metazoan development and widely involved in developmental processes. Particularly in early mesoderm development, it is emerging that a network of T-box genes interacts with Wnt/beta-catenin and Notch/Delta signaling pathways, among others, to control the important processes of mesoderm specification, somite segmentation, and left/right body axis determination."
Kumar A, Lualdi M, Lewandoski M, Kuehn MR. Broad mesodermal and endodermal deletion of Nodal at postgastrulation stages results solely in left/right axial defects. Dev Dyn. 2008 Sep 4. (More? Factors - Nodal)
"Nodal signaling is a critical regulator of multiple aspects of early vertebrate development including asymmetry along the left/right (LR) axis. ...complete deletion of Nodal before its normal transient expression in the early somite stage lateral plate mesoderm, thereby causing severe LR developmental defects. No other abnormalities were found, suggesting that Nodal signaling has no additional essential functions"
Links: Reviews | Articles | Search PubMed | Online Textbooks | Search Textbooks | Journals | Glossary
Search Sep 2008 "left right axis development" 412 reference articles of which 71 were reviews.
Search PubMed Now: term= left right axis development | Nodal signaling | intracellular calcium signaling
Schier AF, Shen MM. Nodal signalling in vertebrate development. Nature. 2000 Jan 27;403(6768):385-9. Review.
Supp
DM, Potter SS, Brueckner
M. Molecular motors: the driving force behind
mammalian left-right development.
Trends Cell Biol. 2000
Feb;10(2):41-5. Review.
Tamura K, Yonei-Tamura S, Belmonte JC. Molecular basis of left-right asymmetry. Dev Growth Differ. 1999 Dec;41(6):645-56. Review.
Levin M. Left-right asymmetry and the chick embryo. Semin Cell Dev Biol. 1998 Feb;9(1):67-76.
Yost HJ. Left-right development in Xenopus and zebrafish. Semin Cell Dev Biol. 1998 Feb;9(1):61-6. Review.
Brown NA, McCarthy A, Seo J. Development of the left-right axis. Ciba Found Symp. 1992;165:144-54; discussion 154-61. Review.
Morgan
MJ. The asymmetrical genetic determination of
laterality: flatfish, frogs and human
handedness.
Ciba Found Symp.
1991;162:234-47; discussion 247-50. Review.
Blum
M, Steinbeisser H, Campione M,
Schweickert
A. Vertebrate left-right asymmetry: old studies
and new insights.
Cell Mol Biol (Noisy-le-grand).
1999 Jul;45(5):505-16. Review.
PMID: 10512183; UI: 99440734
Yost
HJ. Left-right development from embryos to
brains. Dev Genet. 1998;23(3):159-63.
Review.
Casey
B. Two rights make a wrong: human left-right
malformations. Hum Mol Genet.
1998;7(10):1565-71. Review.
Kosaki
K, Casey B. Genetics of human left-right axis
malformations. Semin Cell Dev Biol. 1998
Feb;9(1):89-99. Review.
Supp
DM, Brueckner M, Potter
SS. Handed asymmetry in the mouse: understanding
how things go right (or left) by studying how
they go wrong. Semin Cell Dev Biol. 1998
Feb;9(1):77-87. Review.
Levin M. Left-right asymmetry and the chick embryo. Semin Cell Dev Biol. 1998 Feb;9(1):67-76.
Yost HJ. Left-right development in Xenopus and zebrafish. Semin Cell Dev Biol. 1998 Feb;9(1):61-6. Review.
Brown NA, McCarthy A, Seo J. Development of the left-right axis. Ciba Found Symp. 1992;165:144-54; discussion 154-61. Review.
Morgan
MJ. The asymmetrical genetic determination of
laterality: flatfish, frogs and human
handedness. Ciba Found Symp.
1991;162:234-47; discussion 247-50. Review.
Garic-Stankovic A, Hernandez M, Flentke GR, Zile MH, Smith SM. A ryanodine receptor-dependent Cai2+ asymmetry at Hensen's node mediates avian lateral identity. Development. 2008 Oct;135(19):3271-80.
Baker K, Holtzman NG, Burdine RD. Direct and indirect roles for Nodal signaling in two axis conversions during asymmetric morphogenesis of the zebrafish heart. Proc Natl Acad Sci U S A. 2008 Sep 16;105(37):13924-9.
Wardle FC, Papaioannou VE. Teasing out T-box targets in early mesoderm. Curr Opin Genet Dev. 2008 Sep 5.
Kumar A, Lualdi M, Lewandoski M, Kuehn MR. Broad mesodermal and endodermal deletion of Nodal at postgastrulation stages results solely in left/right axial defects. Dev Dyn. 2008 Sep 4.
The first page of Developmental and System Notes usually contains some information about mechanisms of development that include molecular mechanisms. In order to keep the introductory page simple, detailed molecular mechanisms have been placed on a separate page (Page 11) of each section of notes. Below is a list of direct links to specific Molecular Development Pages.
| Molecular System Notes |
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| Axis Formation | Early | Limbs |
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Signaling during development, though complex, can also be grouped into a few specific classes. These mechanisms have also been listed and described briefly on Signaling Mechanisms page.
Lecture Notes |
Please note that these notes only relate to an earlier Course and not all Lecture notes and research material have been transferred. |
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Simple pictures illustrating the early events of fertilization. |
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Figures and text relating to early events of spinal cord formation. |
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Text relating to the molecular events of sex determination in the embryo. |
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A short comparison of establishing positional information in embryos. |
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The fly mutation that opened the field of Hox Genes and the conservation of pattern formation control mechanisms between species in embryonic development. |
| A | B | C | D | E | F | G | H | I | J | K | L | M | N | O | P | Q | R | S | T | U | V | W | X | Y | Z | Numbers |
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New 2010 Site
Enjoyed this site? Visit the New 2010 Site!
This current page includes both body and organ left/right axis formation information. While the final animals are significantly different, the mechanisms that regulate axis formation have been shown to have a number of common molecular pathways and signals.
Please email Dr Mark Hill if you wish to make a comment about this current project.