scholarly journals Reversal of left-right asymmetry induced by aberrant Nodal signaling in the node of mouse embryos

Development ◽  
2009 ◽  
Vol 136 (23) ◽  
pp. 3917-3925 ◽  
Author(s):  
S. Oki ◽  
K. Kitajima ◽  
S. Marques ◽  
J. A. Belo ◽  
T. Yokoyama ◽  
...  
Keyword(s):  
Mouse Embryos ◽  
Nodal Signaling ◽  
Left Right Asymmetry

scholarly journals Cerberus–Nodal–Lefty–Pitx signaling cascade controls left–right asymmetry in amphioxus

2017 ◽  
Vol 114 (14) ◽  
pp. 3684-3689 ◽  
Author(s):  
Guang Li ◽  
Xian Liu ◽  
Chaofan Xing ◽  
Huayang Zhang ◽  
Sebastian M. Shimeld ◽  
...  
Keyword(s):  
Gene Expression ◽  
Transcription Factor ◽  
Feedback Loops ◽  
Signaling Cascade ◽  
Nodal Signaling ◽  
Transcription Activator ◽  
Gene Expression Cassette ◽  
Left Right Asymmetry ◽  
The Right ◽  
Target Transcription Factor

Many bilaterally symmetrical animals develop genetically programmed left–right asymmetries. In vertebrates, this process is under the control of Nodal signaling, which is restricted to the left side by Nodal antagonists Cerberus and Lefty. Amphioxus, the earliest diverging chordate lineage, has profound left–right asymmetry as a larva. We show that Cerberus, Nodal, Lefty, and their target transcription factor Pitx are sequentially activated in amphioxus embryos. We then address their function by transcription activator-like effector nucleases (TALEN)-based knockout and heat-shock promoter (HSP)-driven overexpression. Knockout of Cerberus leads to ectopic right-sided expression of Nodal, Lefty, and Pitx, whereas overexpression of Cerberus represses their left-sided expression. Overexpression of Nodal in turn represses Cerberus and activates Lefty and Pitx ectopically on the right side. We also show Lefty represses Nodal, whereas Pitx activates Nodal. These data combine in a model in which Cerberus determines whether the left-sided gene expression cassette is activated or repressed. These regulatory steps are essential for normal left–right asymmetry to develop, as when they are disrupted embryos may instead form two phenotypic left sides or two phenotypic right sides. Our study shows the regulatory cassette controlling left–right asymmetry was in place in the ancestor of amphioxus and vertebrates. This includes the Nodal inhibitors Cerberus and Lefty, both of which operate in feedback loops with Nodal and combine to establish asymmetric Pitx expression. Cerberus and Lefty are missing from most invertebrate lineages, marking this mechanism as an innovation in the lineage leading to modern chordates.

scholarly journals Designer Nodal/BMP2 Chimeras Mimic Nodal Signaling, Promote Chondrogenesis, and Reveal a BMP2-like Structure

2013 ◽  
Vol 289 (3) ◽  
pp. 1788-1797 ◽  
Author(s):  
Luis Esquivies ◽  
Alissa Blackler ◽  
Macarena Peran ◽  
Concepcion Rodriguez-Esteban ◽  
Juan Carlos Izpisua Belmonte ◽  
...  
Keyword(s):  
Crystal Structure ◽  
Chondrogenic Differentiation ◽  
Biochemical Study ◽  
Adipose Derived Stem Cells ◽  
Nodal Signaling ◽  
Induced Differentiation ◽  
Therapeutic Implications ◽  
Heart Looping ◽  
Cartilage Injuries ◽  
Left Right Asymmetry

Nodal, a member of the TGF-β superfamily, plays an important role in vertebrate and invertebrate early development. The biochemical study of Nodal and its signaling pathway has been a challenge, mainly because of difficulties in producing the protein in sufficient quantities. We have developed a library of stable, chemically refoldable Nodal/BMP2 chimeric ligands (NB2 library). Three chimeras, named NB250, NB260, and NB264, show Nodal-like signaling properties including dependence on the co-receptor Cripto and activation of the Smad2 pathway. NB250, like Nodal, alters heart looping during the establishment of embryonic left-right asymmetry, and both NB250 and NB260, as well as Nodal, induce chondrogenic differentiation of human adipose-derived stem cells. This Nodal-induced differentiation is shown to be more efficient than BPM2-induced differentiation. Interestingly, the crystal structure of NB250 shows a backbone scaffold similar to that of BMP2. Our results show that these chimeric ligands may have therapeutic implications in cartilage injuries.

Retinoic acid is required in the mouse embryo for left-right asymmetry determination and heart morphogenesis

Development ◽  
1999 ◽  
Vol 126 (12) ◽  
pp. 2589-2596 ◽  
Author(s):  
C. Chazaud ◽  
P. Chambon ◽  
P. Dolle
Keyword(s):  
Retinoic Acid ◽  
Vitamin A ◽  
Mouse Embryo ◽  
Time Course ◽  
Retinoic Acid Receptor ◽  
Mouse Embryos ◽  
Anteroposterior Patterning ◽  
Heart Looping ◽  
Left Right Asymmetry

Determination of the left-right position (situs) of visceral organs involves lefty, nodal and Pitx2 genes that are specifically expressed on the left side of the embryo. We demonstrate that the expression of these genes is prevented by the addition of a retinoic acid receptor pan-antagonist to cultured headfold stage mouse embryos, whereas addition of excess retinoic acid leads to their symmetrical expression. Interestingly, both treatments lead to randomization of heart looping and to defects in heart anteroposterior patterning. A time course analysis indicates that only the newly formed mesoderm at the headfold-presomite stage is competent for these retinoid effects. We conclude that retinoic acid, the active derivative of vitamin A, is essential for heart situs determination and morphogenesis.

scholarly journals Left–right asymmetry in the level of active Nodal protein produced in the node is translated into left–right asymmetry in the lateral plate of mouse embryos

2011 ◽  
Vol 353 (2) ◽  
pp. 321-330 ◽  
Author(s):  
Aiko Kawasumi ◽  
Tetsuya Nakamura ◽  
Naomi Iwai ◽  
Kenta Yashiro ◽  
Yukio Saijoh ◽  
...  
Keyword(s):  
Mouse Embryos ◽  
Lateral Plate ◽  
Left Right Asymmetry

scholarly journals Left-Right Asymmetry in the Sea Urchin Embryo Is Regulated by Nodal Signaling on the Right Side

2005 ◽  
Vol 9 (1) ◽  
pp. 147-158 ◽  
Author(s):  
Véronique Duboc ◽  
Eric Röttinger ◽  
François Lapraz ◽  
Lydia Besnardeau ◽  
Thierry Lepage
Keyword(s):  
Sea Urchin ◽  
Nodal Signaling ◽  
Sea Urchin Embryo ◽  
Left Right Asymmetry ◽  
The Right
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