Origin and Diversification of Hormone Systems

We are interested in the evolution of hormone systems. Central to our work is the exploration of a novel invertebrate model system, Platynereis dumerilii. This marine worm exhibits a unique combination of ancestral-type genomic characteristics not found in insect and nematode model species. Therefore, Platynereis is highly interesting for comparison with the vertebrate hormone system, and for our understanding of marine life.
 
JUST PUBLISHED:
 
F. Christodoulou, F. Raible, R. Tomer, O. Simakov, K. Trachana, S. Klaus, H. Snyman, G.J. Hannon, P. Bork and D. Arendt (2010). Ancient animal microRNAs and the evolution of tissue identity. Nature, published online 31st January 2010.
 
 
(1) Exploring a slowly-evolving marine species
Life began in the sea, and many of the key evolutionary changes occurred in the context of a marine environment. In contrast, most of our knowledge on molecular, developmental and physiological processes derives from non-marine model species, e.g. the insect Drosophila melanogaster or the nematode Caenorhabditis elegans. Recent studies, however, indicate that insect and nematode lineages evolved at elevated rates. In contrast, several marine animals such as the annelid worm Platynereis have retained more ancestral features in their genomes, transcriptomes and cell types. Platynereis is therefore ideally suited to complement the conventional model systems to understand how animal features evolved. We have been among the first ones to explore this unique position of Platynereis by studying the evolution of animal gene repertoires, gene structure, cell types, and, recently, the expression of microRNAs (1-4). Intriguingly, Platynereis also possesses a vertebrate-type repertoire of hormones and hormone-synthesizing/modifying enzymes that point towards a deep conservation of animal hormone systems. As Platynereis is a simple invertebrate, these hormones usually demarcate only a few specific cells, facilitating their subsequent analysis (see Fig. 1). Using functional genomic tools, we study both the development of the worm’s hormone system and its function in the marine ecosystem.
 
 
(2) Regulatory genomics
Development can be understood as the sequential activation of gene regulatory networks encoded in the genome. Due to the central position of Platynereis in animal phylogeny, a detailed understanding of its developmental gene regulatory networks provides key data for the comparison with other model systems and helps us to reconstruct how these networks originated and diverged over evolutionary time. Driven by this interest, we are pioneering the establishment of regulatory genomic tools for Platynereis (Fig. 2). These include phylogenetic footprinting, transgenesis, laser-assisted microdissection, next-generation sequencing and functional interference. This toolbox will allow us to label and investigate hormonal cells in Platynereis with cellular resolution, and to complement functional studies such as injections of hormones or inhibitors into the animal.
 

(3) The hormonal control of reproduction and regeneration
What could be the function of the ancestral-type hormones in Platynereis? One of the systems that we aim to dissect is the hormonal machinery orchestrating reproduction and regeneration. Platynereis is an excellent object for this field, because a rich body of classical experiments already provides us with detailed hypotheses about these hormones: For instance, classical transplantations uncovered that the Platynereis brain is required to orchestrate both reproduction and regeneration. Decapitated animals undergo asynchronous maturation, but heads implanted into their coelomic cavity revert this effect. Subsequent experiments revealed that the responsible activity – termed the “brain hormone” – is conserved between species and maps to a small part of the Platynereis medial brain (Fig. 3). Thanks to our molecular analyses, we already know that cells in these regions express a set of conserved hormones. These factors, along with the new molecular toolkit, now provide a powerful entry point into the dissection of hormonal function in an ancestral-type invertebrate.



 
 

Fig. 1. Platynereis posseses a simple, yet slowly-evolving hormone system.
(A) The extent of evolutionary divergence (arrow) is high for conventional nematode and insect model systems (left). In contrast, it is low for Platynereis and vertebrate models (right). Therefore, Platynereis is well suited to study the origin of vertebrate features, including hormones. (B-D) The simplicity of the Platynereis hormonal system is exemplified by the detection of selected peptide hormones using whole-mount in situ hybridisation. In each case, only a few selected cells (arrowheads) are stained in the whole Platynereis brain.

 
Fig. 2. Shedding light on gene regulatory networks.
(A) Genomic alignments between Platynereis and another annelid worm, Nereis, reveal candidate noncoding elements (NCE) that integrate regulatory information. “Ex” indicates conserved coding exons.
(B) 1-day old larva expressing green fluorescent protein (GFP) from an injected reporter construct. GFP expression in the prototroch (pt, asterisk) and apical tuft (at, arrowhead) reflect the activity of the regulatory element used in the injection construct.

Fig. 3. Hormonal orchestration of regeneration and reproduction by the medial Platynereis brain.
(A) Classical transplantation studies revealed that immature Platynereis heads are the source for an endocrine brain hormone inhibiting maturation and supporting regeneration. (B) Implantations of small brain fragments (blue) map the source of the brain hormone to the medial Platynereis brain. The new molecular toolbox for Platynereis allows for the first time to identify and study the cellular circuits and hormonal cues responsible for these functions.

SELECTED REFERENCES:
1. F. Raible et al., Science 310, 1325 (Nov 25, 2005).
2. K. Tessmar-Raible et al., Cell 129, 1389 (Jun 29, 2007).
3. A. S. Denes et al., Cell 129, 277 (Apr 20, 2007).
4. F. Christodoulou et al., Nature  (Jan 31, 2010).