BRAIN INCREASE PROJECT

The ontogenetic, phylogenetic and molecular bases of human brain evolution

Co-ordinators

Prof. Brunetto Chiarelli

Dr. Maria Giulia Fiore

Dr. Stefano Magherini

Object of the present research program (with Prof. Marco RUGGIERO at University of Florence, national staff leader) is the study of the evolution of the central nervous system of non-human and human Primates, using the genomic sequences of OTX1, OTX2, EMX1, EMX2, PHOX2a, PHOX2b, MEIS1 and MEIS genes. The first stages of embryonic development are controlled by different families of particular genes, called Homeobox, which regulate the disposition of the different parts of the body along its principal axis. Edoardo Boncinelli, the Italian researcher who studied them in the Drosophila melonogaster, defined them “architect-genes” because they trace the general project of the “house”. They are regulatory genes, which control the activity of other genes that act as “executors”.

With this project we aim to study these genes in humans and to try to understand their function during the course of the ontogenetic and phylogenetic development of the brain of human and non-human Primates (Pan troglodytes, Pongo pygmaeus, Macaca mulatta and Callithrix jacchus).

Indeed the neocortex is organized into repeated units of neurons, which in turn are organized in columnar structures on which the evolutionary variability of the human brain mass is based, and the molecular interactions which control the organization of this structure will also be the object of this research project.

Moreover, the information collected on the functioning of these Homeobox genes for the development of the neocortex, will provide the possibility of identifying and characterize some of these genes and their mutants involved in the pathogenesis of different brain tumors and of correlating alterations of genes with these pathological conditions.

Trying to understand at the level of these genes, the differences first at a nucleotidic level and then at an aminoacidic level, between the different Primates examined, could allow us to pinpoint genetically the mechanism that was activated so that the quantitative leap in cerebral mass, which happened in the human species and not in other living aninmal species took place.

Thus, we want to create a sort of genetic “streetmap” of the human brain, which allows us to be able to identify the differences at a proteic level between the human brain and the brain of non-human Primates.

Besides, as the structure of neural cells is very peculiar, it needs to be studied even with the most advanced and innovative biomolecular methodologies. For this reason, the evolution of the brain will be seen under different aspects. With this in mind, our collegues in Pavia (led by Prof. Massimo PREGNOLATO)will run experiments of co-localization of neuropeptides and tubulin, which mark the whole neural network, which will enable us to assess the position, distribution and abundance of the cells positive to neuropeptides in relation to other neural cells. They will be joined by the work of the Urbino Research Unit (led by Prof. Armando GREGORINI), which instead will further investigate the epigenetic ways which regulate the expression and functionality of some genes that play an important role in the development of cerebral regions and language (including the 8 genes object of the project).

Dr. Stefania PACINI, instead, and her Unit in Firenze will proposethe use of the MacLean's model to compare the different brain regions in humans and in hominoids, and will seek to delineate different cortical brain areas from their endocranial prints in remains of fossil hominids.

Finally, the Perugia Unit (led by Dr. Michela CODINI)will evaluate whether the expression of Homeobox genes in the antennal and optical ganglia, plays a role in the social behavior of worker bees. This is intended to be a complementary research model, since the Homeobox genes have been discovered for the first time in an insect, the fruit fly Drosophila melanogaster.

Not to be neglected is the precious contribution of two external consultants. Jeffrey SCHWARTZ, professor of Anthropology, History and Philosophy of Science at the University of Pittsburgh (USA), one of the leading world experts, with a profound knowledge of all the most important fossil remains of the ancestors of the human evolutionary line, who will provide some of the fossil remains object of part of the whole research. Instead, Jacopo ANNESE, Head of the Brain Observatory at the University of California, San Diego (USA), will make available the use of imaging techniques based both on the Structural Magnetic Resonance (sMRI) and the computerized Microscopy, with the aim to obtain large histological slices, mapping the results of the histological analysis on tridimensional images (both at volumetric and at structural models of surface triangulation levels) of the brain, with the aim to localize the genetic expression of the human cerebral tissue, maintaining the anatomical view of the human brain and the brain of the studied Primate species.

Not only Anthropology then, but a multidisciplinar staff with a holistic view, and the evolution of the brain “seen” not only from a merely anatomic-quantitative point of view, but also biomolecular, biochemical, medical and anatomic-histologic.