Le cerveau multidimensionnel

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Development and Evolution of the Forebrain

Team leader : Sylvie Rétaux


1- Research interests

The vertebrate forebrain has undergone an extraordinary diversification in the course of evolution. For instance, could anyone see that the mammalian cerebral cortex, with its well-known organization into 6 layers, and the so-called everted pallium of teleost fishes, are homologous brain regions ?
Using an evolutionary developmental approach, we aim to understand the genetic and cellular mechanisms which govern the unity (homology) and the differences (diversification) present in the forebrains of various vertebrates. And we study the consequences of the observed developmental variations in terms of adaptive behaviors. To this end, we use an original animal model : the blind cavefish Astyanax mexicanus, which we consider as a “natural mutant”. During its adaptation to life in total and permanent darkness, this fish lost its eyes (and its pigmentation).


2- Projects

Astyanax mexicanus, also called the Mexican tetra, is a freshwater characiform fish with a large distribution in Central America. The eyed, river-dwelling forms and the eyeless, cave-dwelling forms of this species are used as models for evolutionary biology, including for the study of the evolution of the nervous system. During their adaptation to life in their dark habitat, cavefish populations have lost their eyes and their pigmentation, but they have also developed some traits that are more “useful” for cave life, such as enhanced olfaction and lateral line, large jaws and more teeth, and a series of specific behaviors which are considered as adaptive.
There are 29 known caves hosting Astyanax mexicanus cavefish populations. Some of these populations represent cases of convergent evolution, resulting from independent colonization events. They thus permit to study developmental micro-evolution and the mechanisms for generation of morphological and behavioral evolution.
In the lab, we mostly use the blind cavefish originating from the Pachón cave.

We work along three axes of research :

  • 1- Developmental evolution of the cavefish forebrain.

What are the developmental mechanisms leading to eye loss in cavefish embryos ? What are the consequences on other parts of the developing forebrain ?
This part of our project, said « evo-devo », aims at comparing the morphogenesis, the patterning, the neurogenesis and the neuronal specification in embryos of the two morphs. We wish to understand the interactions between neural plate organizer centers which secrete morphogen molecules of the Hedgehog, Fgf, Dkk1b or Bmp families. Modifications in these signaling centers are at the origin of eye loss in cavefish, but also shape the neural plate and neural tube and are responsible for important and possibly adaptive modifications in other parts of the forebrain (olfactory bulbs, hypothalamus). We also analyze the impact of these signaling centers on the development of sensory placodes, from which the lens (apoptotic in cavefish), the olfactory epithelium, or the lateral line originate.

  • 2- Behavioral evolution of cavefish.

What are the neural bases of the multiple behavioral changes, sometimes grouped under the term “behavioral syndrome”, in the blind cavefish ? Are these changes adaptive ?
In this part of the team project, our aim is to establish a link between the early modifications of patterning and neurogenesis that we have observed in cavefish with the development of neuronal networks and the behaviors they govern. We study social behaviors (aggressiveness, hierarchy), homeostatic behaviors (feeding) and the evolution of sensory capabilities (olfaction) in cavefish, always in a comparative manner with its surface fish counterparts. Finally, we also try whenever possible to do field work in order to analyze cavefish behavior in its natural environment.

  • 3- Molecular evolution of the cavefish transcriptome and genome.

Which mutations are at the origin of the cavefish phenotypic evolution ? What are the evolutionary forces at play ?
Through transcriptome-wide analyses, or through studies focusing on particular gene families, we get some information about ongoing evolutionary mechanisms (i.e., selection or drift ? Or both ?), and on the evolutionary history of cavefish populations (i.e., since how long did they colonize the cave environment ?). These studies are performed in collaboration with the group of Didier Casane (LEGS, Gif sur Yvette).
Through candidate gene approaches we have also identified mutations in the coding sequences of particular genes (for example, MAO) or defects in the expression of some transcripts (example : crystallins). We study the functional consequences of these genetic modifications in cavefish.

A few words about our Astyanax fish facility

Although it is not exactly a “platform”, we have set up an Astyanax facility in the central animal building (it is unique in France). We are now breeding surface fish and the population of cavefish called Pachón.
Thanks to the people who took care of them along the years, and who gave us valuable advices : Stéphane Père, Magalie Bouvet, Diane Denis, Matthieu Simion, Laurent Legendre, Krystel Saroul, Victor Simon, Louise Vernier.
We are also indebted to Bill Jeffery, who brought us in 2004 the first adults to start our colony, and who got us started in the Astyanax world.

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