A Temporal Window for Signal Activation Dictates the Dimensions of a Nodal Signaling Domain.
Morphogen signaling is critical for the growth and patterning of tissues in embryos and adults, but how morphogen signaling gradients are generated in tissues remains controversial. The morphogen Nodal was proposed to form a long-range signaling gradient via a reaction-diffusion system, on the basis of differential diffusion rates of Nodal and its antagonist Lefty. Here we use a specific zebrafish Nodal biosensor combined with immunofluorescence for phosphorylated Smad2 to demonstrate that endogenous Nodal is unlikely to diffuse over a long range. Instead, short-range Nodal signaling activation in a temporal window is sufficient to determine the dimensions of the Nodal signaling domain. The size of this temporal window is set by the differentially timed production of Nodal and Lefty, which arises mainly from repression of Lefty translation by the microRNA miR-430. Thus, temporal information is transformed into spatial information to define the dimensions of the Nodal signaling domain and, consequently, to specify mesendoderm.
Developmental Signalling, The Francis Crick Institute, Lincoln's Inn Fields Laboratory, 44 Lincoln's Inn Fields, London WC2A 3LY, UK.
Antonius L
AL
van Boxtel
Developmental Signalling, The Francis Crick Institute, Lincoln's Inn Fields Laboratory, 44 Lincoln's Inn Fields, London WC2A 3LY, UK.
John E
JE
Chesebro
Developmental Signalling, The Francis Crick Institute, Lincoln's Inn Fields Laboratory, 44 Lincoln's Inn Fields, London WC2A 3LY, UK.
Claire
C
Heliot
Developmental Signalling, The Francis Crick Institute, Lincoln's Inn Fields Laboratory, 44 Lincoln's Inn Fields, London WC2A 3LY, UK.
Marie-Christine
MC
Ramel
Experimental Histopathology, The Francis Crick Institute, Lincoln's Inn Fields Laboratory, 44 Lincoln's Inn Fields, London WC2A 3LY, UK.
Richard K
RK
Stone
Developmental Signalling, The Francis Crick Institute, Lincoln's Inn Fields Laboratory, 44 Lincoln's Inn Fields, London WC2A 3LY, UK. Electronic address: caroline.hill@crick.ac.uk.
Caroline S
CS
Hill
D000818:Animals; D015374:Biosensing Techniques; D019521:Body Patterning / Q000235:genetics*; D018507:Gene Expression Regulation, Developmental; D055458:Left-Right Determination Factors / Q000096:biosynthesis / Q000235:genetics*; D035683:MicroRNAs / Q000235:genetics*; D055457:Nodal Protein / Q000235:genetics* / Q000378:metabolism; D051899:Smad2 Protein / Q000096:biosynthesis / Q000235:genetics; D015027:Zebrafish / Q000235:genetics / Q000254:growth & development; D029961:Zebrafish Proteins / Q000096:biosynthesis / Q000235:genetics*
D055458:Left-Right Determination Factors; D035683:MicroRNAs; C557527:Mirn430 microRNA, zebrafish; D055457:Nodal Protein; D051899:Smad2 Protein; D029961:Zebrafish Proteins; C117508:lft1 protein, zebrafish; C497786:smad2 protein, zebrafish
Lefty; Nodal; mesendoderm; miR-430; morphogen; temporal signal activation window; zebrafish