CONICET | Buscador de Institutos y Recursos Humanos

Dendrite size and morphology are key determinants of the functional properties of neurons, and brain disorders are due primarily to structural abnormalities of dendrites and their connections. Distinct leucine-rich repeat (LRR) transmembrane proteins are highly expressed in the brain, especially in the hippocampus, where they play a critical role in the organization and function of neural circuits, regulating neurotrophin signaling, coordinating pre- and post-synaptic compartments during excitatory and inhibitory synapse formation and regulating synaptic plasticity. Recently, the LRR protein, Lrig1, has been described as an essential regulator of neurotrophin signaling and dendrite arborization of hippocampal neurons. However, the physiological contribution of Lrig2 for neuronal development remains to be determined. Taking advantage of the post-natal expression of Lrig2 by hippocampal developing neurons, we used gain and loss of function assays to examine how altered Lrig2 expression impacts dendrite morphology and synapse formation in search for specific LRR proteins involved in neurodevelopmental disorders. Here, we show that Lrig2 overexpression exacerbates dendrite complexity by promoting growth and branching, in a LRR domain-dependent manner. Our results also indicate that Lrig2 is expressed in pre- and post-synaptic fractions, where it controls the density of dendritic spines and increases the number of excitatory synaptic contacts in hippocampal neurons