We have investigated early pathways involved in constructing the posterior part of the vertebrate anterior-posterior (A-P) axis.
Investigations of vertebrate axial patterning have emphasised the importance of dorsal Spemann organiser mesoderm in the gastrula Experiments by Nieuwkoop and collaborators led to the further conclusions that dorsal mesoderm emits two types of signals Activation signals neuralise ectoderm to a (forebrain specific) ground state. A graded transformation signal progressively modifies (posteriorises) neural tissue, and thereby creates the axial pattern. We reevaluated  these ideas. We found evidence that early posterior regulators are first expressed in a non organiser cascade in ventrolateral mesoderm, and that neural transformation actually reflects an interaction between this posteriorising cascade and organiser cascades.

We detected a temporally colinear sequence of Hox gene expression in ventrolateral mesoderm in the gastrula. This ventrolateral cascade is autonomous. It can be isolated by ventralisation (via UV treatment of the zygote, which blocks formation of the organiser). In isolation, it does not establish axial structures or a spatial AP pattern: the temporally colinear sequence of Hox expression simply runs through from beginning to end without generating stable Hox expression zones. Definitive positional information for the posterior part of the anterior-posterior (AP) axis is generated by a timing device. utilising timed interactions between the temporally colinear mesodermal Hox cascade and the Spemann organiser. These occur when convergence and extension movements continually bring new mesodermal cells within range of Spemann organiser signals during the course of gastrulation. The organiser stabilises timed information from the ventrolateral Hox cascade and thereby stably establishes a sequence of specific stable AP positional identities. Stabilisation involves transfer of Hox information from mesoderm to the overlying neural tissue and is sequential. The first ventrolateral mesoderm which is stablised by interacting with the organiser carries an early (anterior) Hox code. Mesoderm arriving sequentially later carries a sequentially later (more posterior) Hox code. We argue that this mechanism is general, among the vertebrates. These concepts provide a framework for investigating the functions of axial patterning genes. We are investigating different aspects of this mechanism.