Designing the Bodyplan: Developmental Mechanisms

 

Report

 

General Strategy

This was a meeting about concepts. We were concerned with “Developmental Principles” or “Developmental Mechanisms” which implement the embryo's body plan. We focussed on four aspects (below) which are important for the making the embryo’s main body axis

These topics were presented and discussed in a workshop at the Lorentz Center in the University of Leiden, attended by 43 participants, ranging from the leading workers in the field to Ph.D. students and master students.

The topics were highlighted by presentations and then discussed, using highly interactive panel discussions which were initiated by the speakers answering some main questions  and  then continued with questions from the floor. We were lucky enough to have some very extrovert, challenging and active participants and animated discussions continued during the walks through the June countryside to and from our hotel; during  the evenings; during a barbecue on the beach at Katwijk and a boat trip through the Kaag (a famous lake chain near Leiden) and in short at every possible opportunity. Because the meeting was about concepts, it included a session about theoretical models and theoreticians (who are excellent discussants). Due to the connectedness of the topics, it was inevitable that most were spread over different sessions. Where a talk connected two topics, a choice was made.

The topics, speakers and some of the main questions were as follows.

 

1/ Making the axial pattern.

Two principles are  important for making different zones along the main body axis.

a/ Concentration gradients. A key mechanism is that cells respond to quantitatively different concentration ranges in a concentration gradient of an extracellular signal molecule (morphogen) and this causes them to express qualitatively different genes. Graded quantitative information is thereby converted into qualitative information, This provides a mechanism that can generate sequential zones of different cell types, for example, along the embryo’s main axis. Gradients and their likely importance were ably introduced by Lewis Wolpert who pioneered this idea in the ‘60s. The topic was then explored for three well established axial gradients. Wnts (Rik Korswagen); Cdx (Steve Gaunt); retinoids (Malcolm Maden) A notable feature of this session was the demonstration, by Malcolm Maden, that retinoids pattern the neck region of the axis in all three germ layers in parallel.

 

b/ Timing mechanisms. A biological clock can also generate a spatial pattern. A key example here is the somitogenesis clock, a mechanism in which an oscillating system of gene expression is measured off in time to deliver repeating spatial units (somites) along the main body axis. This idea first featured in theoretical models in the ‘70s. It has now been clearly demonstrated by diect experimental evidence by Pourquie and his collaborators. There were five presentations on timing. Claudio Stern, with the role of timing in specifying and regionalising the brain. Tony Durston with his Hox timing model. Olivier Pourquie, Stan Mare and Tatiana Resende on somitogenesis. Highlights here were the spectacular advances in somitogenesis, Pourquie presented  his real time visualisation of the somitogenesis oscillator and his microarray analysis of its oscillating gene expression.

 

2/ The Hox module:

One way of generating qualitatively different zones along an axis is where a chromosomal complex acts as a functional unit such that the physical order of the genes in the  complex provides information for timing and/or or for spatial location of gene expression. The classical examples here are the Hox gene complexes. The hox genes were discovered in the ‘70s by Walter Gehring among others and Hox colinearity was first documented in vertebrates by Denis Duboule among others. We  examine how Hox complexes are regulated  and how these function in delivering patterning information along the main body axis.

This topic was covered by 7 speakers; Walter Gehring; Denis Duboule; Alain Prochiantz; Joost Woltering; Jacqueline Deschamps; Olivier  Pourquie; Tony Durston. This topic was, of necessity rather scattered over different sessions. Highlights from this topic were: the conclusions from Walter Gehring and Joost Woltering that posterior prevalence can depend on protein-protein interactions or on translational control via microRNA’s respectively. This collinear property seems to be collinear of necessity (and is anyway anterior prevalence for 3’ Drosophila hox genes). Its mechanism is presumably secondary. Prochiantz gave his usual brilliant exposition of homeoprotein transfer. Denis Duboule argued for evolution of different forms of hox colinearity from an amphioxus like hox cluster and pointed out that the highly compacted and collinear hox clusters found in vertebrates so far occur only in vertebrates. Olivier Pouquie’s discovery of temporally collinear hox regulated gastrulation movements clearly links to the Durston group’s discoveries concerning temporally collinear establishment of the hox pattern during gastrulation.

 

3/ Coordinated cell movements.

One of the least well investigated aspects of embryonic development is how embryos develop their shape (morphogenesis) via coordinated cell movements. We focussed on fundamental principles underlying this aspect during main body axis development. Kees Weijer presented his exciting discovery that directional cell movement to a signal source (chemotaxis) mediates morphogenesis of the embryo during axis formation and Pourquie presented his discovery of hox regulated ingression during gastrulation. Ray Keller amazed us all with his exposition of how hitherto undiscovered movements like convergence thickening subtly shape the embryo. Val Wilson reminded us that stem cells and growth are also important and Elena Tzouacanou followed cell lineage retrospectively.

4/Theoretical Models

This meeting was about concepts and it was appropriate we  had a session on theoretical models. This was ably chaired by Hans Meinhardt whose model for the evolution of bilaterality and incorporation of the trunk module never fails to amaze and inspire. Paulien Hogeweg presented a chemoptactic model of gastrulation based on Weijer’s findings and Stan Maree a mathematical development of the (Cooke-Zeeman/Pourquie) clock-wavefront model for somitogenesis Frietson Galis’s human defects in segmentation and Hans Metrz’s evodevo completed a satisfying session

Besides the main topics, there were other exciting aspects. Lewis Wolpert’s presentation of left right asymmetry. Markus Affolter’s brilliant presentation of chemotaxis and other aspects during tracheal morphogenesis, Herman Spaink on Toll; Gabby Krens on ERK’s.

 

Conclusion and perspectives

In conclusion, this field is definitely at a stage where the essence of the A-P patterning mechanism which has eluded investigators for more than 80 years is now finally  within reach.  It is extremely worthwhile to build on the be foundations laid by this meeting.  Measures underway/under discussion are: collecting and distributing the presentations from the meeting and a list of key references; and writing a joint review. The meeting was such a great success that we plan a series of related workshops in the future.

We thank Yolande van der Deijl and Martje Kruk and the Lorentz Center staff fore their really excellent organisation of the meeting. This created an extremely positive atmosphere which contributed greatly to its brilliant success.