CNR - Institute of Neuroscience CNR
Institute of Neuroscience
 

Project

Mechanisms controlling cell positioning during development

Our broad goal is to understand the cellular interactions responsible for the assembly of neural circuits. We use the retina as a model system, and a multidisciplinary approach combining live imaging, neuroanatomy and modeling.

Mechanisms controlling cell positioning during development:

Most neuronal circuitry in the CNS is modular. This is particularly evident in the retina, where cells of the same type are in the same layer and synaptic connections are segregated in distinct layers.

During development, the first features of this modular circuitry to appear are regular monolayered arrays of like-neurons, called retinal mosaics.

 

We devoted much of our recent research to understanding the mechanisms controlling the patterning of these early cell array.

We showed that in most cases, mosaic cells are regularly spaced by a minimal distance rule enacted by local interactions restricted to homotypic cells. To become regularly spaced, mosaic cells use active displacement and killing of improperly spaced cells. During mosaic formation destabilizing the dendrite cytoskeleton reversibly destroys mosaic order. From these findings we derived a model of mosaic formation like the assembly of tensegrity nets, and proposed a model of retinal development based on local interactions (Galli-Resta, TINS 2002; Eglen et al., 2003; Rossi et al., JN 2003; Novelli et al., PBR 2005; Resta et al., Development 2005; Eglen and Galli-Resta, 2006; Novelli et al., VN 2007; Galli-Resta et al., PRER 2008).

 

Models of retinal pathologies

The major risk factor for GLAUCOMA is increased intraocular pressure, but how this leads to neuronal damage is still debated. Using a custom designed bioreactor we developed an in vitro model where retinas can be subjected to controlled pressure insults and neuronal damage quantified. This system has allowed us to identify extracellular ATP as the main mediator of acute pressure-induced neuronal damage (Resta et al. EJN 2007). We also showed that brief pressure increments induce a prolonged inhibition of Endothelin-1 capillary responsiveness, which most likely contributes to abnormal blood flow regulation (Rigosi et al., 2010).

Publications

  • Rigosi E, Ensini M, Bottari D, Leone P, Galli-Resta L (2010) Loss of retinal capillary vasoconstrictor response to Endothelin-1 following pressure increments in living isolated rat retinas. Exp. Eye Res. 90:33-40.
  • Galli-Resta L, Leone P, Bottari D, Ensini M, Rigosi E, Novelli E (2008) The genesis of retinal architecture: an emerging role for mechanical interactions? Prog Retin Eye Res 27:260-83.
  • Resta V, Novelli E, Vozzi G, Scarpa C, Caleo M, Ahluwalia A, Solini A, Santini E, Parisi V, Di Virgilio F, Galli-Resta L (2007) Acute retinal ganglion cell injury caused by intraocular pressure spikes is mediated by endogenous extracellular ATP. Eur. J. Neurosci. 25:2741-54.
  • Resta V, Novelli E, Di Virgilio F, Galli-Resta L (2005) Neuronal death induced by endogenous extracellular ATP in retinal cholinergic neuron density control. Development 132:2873-82.
  • Rossi C, Strettoi E, Galli-Resta L (2003) The spatial order of horizontal cells is not affected by massive alterations in the organization of other retinal cells. J. Neurosci. 23:9924-8.
  • Galli-Resta L (2002) Putting neurons in the right places: local interactions in the genesis of retinal architecture. Trends Neurosci. 25:638-43.
  • Galli-Resta L, Novelli E, Viegi A (2002) Dynamic microtubule-dependent interactions position homotypic neurones in regular monolayered arrays during retinal development. Development 129:3803-14.
  • Reese BE, Galli-Resta L (2002) The role of tangential dispersion in retinal mosaic formation. Prog Retin Eye Res 21:153-68.

Grants

Telethon Italia, project GGP06031 coordinator

Agenzia Spaziale Italiana DMCM project. Coordinator of the Retinal unit

International Institute fur Paraplegia, Project PP84 Coordinator

Collaborations

  • Rachel Wong, Department of Biological Structure, University of Washington, Seattle, USA.
  • Enrica Strettoi
  • Matteo Caleo
  • Maria Cristina Cenni
  • Giovanni Resta, Institute of Informatics and Telematic CNR, PISA, Italy.
  • Stephen Eglen, Cambridge Computational Biology Institute, Cambridge, UK.
  • Wolfgang Berger, ETH - Neuroscience Center Zurich.
  • Cesare Montecucco
  • Ornella Rossetto, Dept of Experimental Biomedical Sciences, University of Padua.
  • Arti Alhuwalia, Dept Elect. Engineering, University of Pisa, Italy.

 

PI photo

Lucia Galli-Resta

Contact information

email  E-mail

email  +39 050 315 3215

Participating staff

David Bottari

Paola Leone