Activities

Development and Maturation of Inhibitory Neurons

Using Neural Stem cells in vitro, and specific mutant mouse strains, we aim to clarify a molecular signature for GABA+ differentiation, and to comprehend the role of Dlx genes in this process. Current results indicate that alterations of the migration, differentiation and neuritogenesis of inhibitory neurons affect cognitive and memory functions of the hippocampus, and may contribute to the risk of epilepsy.

Development of the Olfactory and GnRH System

The development of the olfactory neurons is associated to the genesis and migration of the GnRH neuroendocrine neurons, a complex process that is specifically impaired in the Kallmann Syndrome. The molecules involved in guidance and connectivity of olfactory axons are not well known. We are investigating the role of specific disease genes and microRNAs for olfactory/GnRH development, combining transcription-profiling, analysis of patterns of conserved co-expression and specific animal models. In particular, zebrafish strains that carry fluorescent neurons, such as GnRH::GFP, turn out useful to investigate on the effect of exposure to endocrine-interfering compounds or other environmentally relevant molecules on the development of a variety of hypothalamic neurons.

The Rac GTPase and Models of Intellectual Disability
The small GTPases of the Rho family, and in particular RhoA and Rac1, have been implicated in genetically transmitted intellectual disability conditions, either directly or upon mutation of one of the several regulators of their enzymatic activity in developing neurons. In the case of Rac1 it appears that most genetic mutations causing ID result in a hypoactive Rac1. Based on our previous work on the protein ArhGAP15, a negative regulator of Rac1, we can hypothesize that interfering with the protein::protein interaction
between ArhGAP15 and Rac1 should result in hyperactivation of Rac1. This applied to the condition of hypoactive Rac1 causing ID might restore normal activity and the development of normal neuronal circuitry. We are currently setting up cellular models to prove this hypothesis.

Recently the team has implemented a novel program, funded by the italian Telethon Foundation and by the Ministry of University, for the use of human pluripotent stem cells - hu-iPSc - to explore the effects of pathogenic mutations on human brain development. In particular, the experimental work focuses on a few selected genes that code for protein products that regulate the dynamic of actin cytoskeleton, whose mutations cause rare forms of hereditary Microcephaly and Intellectual Disability.

Group

• Prof. Giorgio Roberto Merlo (PI)
• Carla Liaci
• Lucia Prandi
• Simona Rando
• Sara Palermo
• Lorenzo Licari
• Emma Leonetti
• Giovanni Catapano