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

Citations Over TimeTop 16% of 2007 papers

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.

Related Papers

• → Mouse Lefty2 and Zebrafish Antivin Are Feedback Inhibitors of Nodal Signaling during Vertebrate Gastrulation(1999)374 cited
• → An essential role for maternal control of Nodal signaling(2013)58 cited
• → A role for Vg1/Nodal signaling in specification of the intermediate mesoderm(2013)36 cited
• → Identification of nodal signaling targets by array analysis of induced complex probes(2001)30 cited
• Novel Biochemical And Phenotypical Findings On The Nodal Signaling Components Lefty And Cripto(2015)