Left–right asymmetry in the vertebrate embryo: from early information to higher-level integration

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Although vertebrates seem to be essentially bilaterally symmetrical on the exterior, there are numerous interior left–right asymmetries in the disposition and placement of internal organs. These asymmetries are established during embryogenesis by complex epigenetic and genetic cascades. Recent studies in a range of model organisms have made important progress in understanding how this laterality information is generated and conveyed to large regions of the embryo. Both commonalities and divergences are emerging in the mechanisms that different vertebrates use in left–right axis specification. Recent evidence also provides intriguing links between the establishment of left–right asymmetries and the symmetrical elongation of the anterior–posterior axis.

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The authors thank C. Rodríguez-Esteban for providing chick embryo pictures, S. Shimeld and A. Nishino for communicating results prior to publication, J. Simon for excellent artwork, C. Stern and all the members of JCIB laboratory for fruitful discussions, and M.-F. Schwarz for help in the preparation of this manuscript. A.R. was partially supported by a postdoctoral fellowship from Fundación Inbiomed, Spain. The research on left–right asymmetry in our laboratory is supported by the US National Institutes of Health, the Human Frontier Science Program, and the G. Harold and Leila Y. Mathers Charitable Foundation.

Author information


  1. Center of Regenerative Medicine in Barcelona and Instituci Catalana de Recerca i Estudis Avanats (ICREA), Doctor Aiguader 80, 08003 Barcelona, Spain.

    • Ángel Raya
  2. Gene Expression Laboratory, Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, California 92037, USA.

    • Juan Carlos Izpisúa Belmonte


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Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Juan Carlos Izpisúa Belmonte.


Embryo node

A transient structure located at the anterior tip of the primitive streak in embryos of amniotes (birds, reptiles and mammals); also known as Hensen's node in birds and mammals. The embryo node functions as the gastrula organizer and is therefore functionally equivalent to the dorsal lip of the blastopore (Spemann's organizer) in amphibians and the shield of teleost fishes.

Lateral plate mesoderm

The most lateral region of mesoderm in the neurula-stage vertebrate embryo. Among other structures, it gives rise to the heart, blood vessels, blood cells of the circulatory system, the lining of the body cavities, and all the mesodermal components of the limbs other than muscle.

Primitive streak

A transitory embryonic structure, which is present as a strip of cells, that pre-figures the anterior–posterior axis of the embryo. During gastrulation, embryonic cells progress through the streak.


A taxon of animals that belong to the Bilateria. They are characterized by having a 'second mouth' (giving them their name) — that is, during embryo development, the blastopore becomes the anus, whereas the mouth forms in a secondary anterior location. Deuterostomes are divided into two major clades: Ambulacraria (which includes echinoderms and hemichordates) and Chordata (which includes vertebrates, urochordates and cephalochordates).


Morpholino-modified antisense oligonucleotides (generally known as 'morpholinos') are reagents that are widely used to knockdown gene function in zebrafish by pairing to complementary sequences in gene transcripts and blocking their translation or splicing.

Posterior notochordal plate

The posterior part of the notochordal plate that lies adjacent to the node. It is a flattened, grooved plate, which originates as a result of the fusion and subsequent disappearance of the floor of the notochordal process with the underlying endoderm. The notochordal plate eventually folds inwards to give rise to the notochord.

Midline barrier

A physical and/or molecular barrier that separates the right and left halves of the vertebrate embryo so that the action of long-range side-specific signals does not affect the other side. Physical elements of the barrier are exemplified by the midline derivatives of the node: the notochord and the floorplate. The best-understood molecular component of the midline barrier is the divergent TGFB signal LEFTY1.


The process of metameric segmentation of chordate embryos. In this process, paired blocks of paraxial mesoderm (somites) are specified and segmented following a stereotypical species-specific sequence. In vertebrates, somites form in a bilaterally symmetrical fashion and give rise to bilaterally symmetrical structures, such as the skeletal muscles, the axial skeleton and parts of the dermis.


A structure that is present in the larvae of sea urchins that gives rise to most of the adult tissues. The process of rudiment specification is left–right asymmetrical, originating from the left coelomic pouch and its adjacent lateral ectoderm.


Ventral region of the early neural tube of vertebrate embryos. The medial part of the floorplate is formed by cells that originate in the node or organizer, which induces floorplate-like characteristics in the neural ectoderm-derived cells of the lateral floorplate. The floorplate has important roles during ventral nervous system patterning, including the specification of motor neurons and interneurons, and the differentiation of oligodendrocytes.