Notch activity induces Nodal expression and mediates the establishment of left-right asymmetry in vertebrate embryos.
Left-sided expression of Nodal in the lateral plate mesoderm is a conserved feature necessary for the establishment of normal left-right asymmetry during vertebrate embryogenesis. By using gain- and loss-of-function experiments in zebrafish and mouse, we show that the activity of the Notch pathway is necessary and sufficient for Nodal expression around the node, and for proper left-right determination. We identify Notch-responsive elements in the Nodal promoter, and unveil a direct relationship between Notch activity and Nodal expression around the node. Our findings provide evidence for a mechanism involving Notch activity that translates an initial symmetry-breaking event into asymmetric gene expression.
Raya
Angel
A
Gene Expression Laboratory, The Salk Institute for Biological Studies, La Jolla, California 92037, USA.
Kawakami
Yasuhiko
Y
Rodriguez-Esteban
Concepcion
C
Buscher
Dirk
D
Koth
Christopher M
CM
Itoh
Tohru
T
Morita
Masanobu
M
Raya
R Marina
RM
Dubova
Ilir
I
Bessa
Joaquin Grego
JG
de la Pompa
Jose Luis
JL
Izpisua Belmonte
Juan Carlos
JC
D000818:Animals; D019521:Body Patterning / Q000502:physiology*; D004742:Enhancer Elements, Genetic; D005786:Gene Expression Regulation / Q000502:physiology*; D053823:Hedgehog Proteins; D008565:Membrane Proteins / Q000502:physiology*; D051379:Mice; D055457:Nodal Protein; D020897:Organizers, Embryonic / Q000502:physiology; D011401:Promoter Regions, Genetic; D051880:Receptors, Notch; D015398:Signal Transduction / Q000502:physiology; D012857:Situs Inversus / Q000196:embryology; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000235:genetics* / Q000378:metabolism; D015027:Zebrafish / Q000196:embryology / Q000235:genetics
D053823:Hedgehog Proteins; D008565:Membrane Proteins; D055457:Nodal Protein; C526008:Nodal protein, mouse; D051880:Receptors, Notch; D015534:Trans-Activators; D016212:Transforming Growth Factor beta