title: Sequential and combinatorial inputs from Nodal, Delta2/Notch and FGF/MEK/ERK signalling pathways establish a grid-like organisation of distinct cell identities in the ascidian neural plate.
abstract: The ascidian neural plate has a grid-like organisation, with six rows and eight columns of aligned cells, generated by a series of stereotypical cell divisions. We have defined unique molecular signatures for each of the eight cells in the posterior-most two rows of the neural plate - rows I and II. Using a combination of morpholino gene knockdown, dominant-negative forms and pharmacological inhibitors, we tested the role of three signalling pathways in defining these distinct cell identities. Nodal signalling at the 64-cell stage was found to be required to define two different neural plate domains - medial and lateral - with Nodal inducing lateral and repressing medial identities. Delta2, an early Nodal target, was found to then subdivide each of the lateral and medial domains to generate four columns. Finally, a separate signalling system along the anteroposterior axis, involving restricted ERK1/2 activation, was found to promote row I fates and repress row II fates. Our results reveal how the sequential integration of three signalling pathways - Nodal, Delta2/Notch and FGF/MEK/ERK - defines eight different sub-domains that characterise the ascidian caudal neural plate. Most remarkably, the distinct fates of the eight neural precursors are each determined by a unique combination of inputs from these three signalling pathways.
authors.affiliation: Developmental Biology Unit, Université Pierre et Marie Curie (Paris 6 Villefranche-sur-Mer, France. clare.hudson@obs-vlfr.fr
authors.forename: Clare
authors.initials: C
authors.lastname: Hudson
authors.forename: Sonia
authors.initials: S
authors.lastname: Lotito
authors.forename: Hitoyoshi
authors.initials: H
authors.lastname: Yasuo
mesh_terms: D000818:Animals; D001483:Base Sequence; D019521:Body Patterning / Q000502:physiology; D002938:Ciona intestinalis / Q000196:embryology* / Q000235:genetics / Q000378:metabolism*; D017931:DNA Primers / Q000235:genetics; D005346:Fibroblast Growth Factors / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental; D018390:Gene Targeting; D047908:Intracellular Signaling Peptides and Proteins; D020935:MAP Kinase Signaling System; D008565:Membrane Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D054258:Neural Plate / Q000196:embryology* / Q000378:metabolism*; D055457:Nodal Protein; D051880:Receptors, Notch / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D016212:Transforming Growth Factor beta / Q000172:deficiency / Q000235:genetics / Q000378:metabolism
chemical_list: D017931:DNA Primers; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D055457:Nodal Protein; D051880:Receptors, Notch; D016212:Transforming Growth Factor beta; C064045:delta protein; D005346:Fibroblast Growth Factors