Vision is one of the most crucial senses for humans, and it depends on retinal function. Mutations in retinal genes are non-lethal and can cause specific and disabling forms of retinal degenerations, such as Retinitis Pigmentosa or macular degeneration. Retinal degenerations represent the major cause of blindness in the world, for which we still have no cure. One of the reasons is that the molecular mechanisms underlying the death of photoreceptors still need to be fully elucidated. For this, we need to develop effective models able to recapitulate the disease and that can be used to develop new therapeutic approaches.
Our laboratory studies the factors driving the differentiation and survival of retinal progenitor cells and neurons. We aim to identify the mechanisms that maintain retinal function, and how these can be disrupted in pathological conditions. For this, we use a multidisciplinary approach, from three-dimensional cell cultures to genetic models.
Specific projects are:
- Generation of a zebrafish model of a novel genetic retinal degeneration. We are using both morpholino antisense oligonucleotides and genome editing by CRISPR/Cas9 to study the role of a photoreceptor-specific extracellular matrix protein involved in human Retinitis Pigmentosa.
- Characterization of retinal inducing factors and their pathways of actions during in vivo retinogenesis and in ex-vivo explants. We are focusing on the interactions among different growth factors signaling pathways.
- Characterization of an alginate-based three-dimensional culture system for neural stem cells. We will shortly begin to test the applicability of this system in vivo, in brain injury models. Project in collaboration with Prof. Motta, University of Trento, and Dr. Zanier, Mario Negri Institute.
- We are analyzing the retina of a mouse model of autism spectrum disorders, the Engrailed 2 knock-out mouse, to understand if alterations in visual perception due to retinal defects can be linked to this disease. Project in collaboration with Prof. Gargini, University of Pisa, and Prof. Bozzi, University of Trento.
- Simona Casarosa, PI
- Andrea Messina, Post-doc
- Alessandra Speccher, PhD Student
- Xuwen Zhang, PhD student
Maria Elena Castellini, Graduate Fellow
Francesca Agostinacchio, Master Student
- Yuri Bozzi, Neurodevelopmental Disorders Research Group, CIMeC, University of Trento, Italy
Maria Claudia Gargini, University of Pisa, Italy
- Antonella Motta, BIOtech, University of Trento, Italy
- Elisa Zanier, Mario Negri Institute, Milan, Italy
Bozzi Y, Provenzano G, Casarosa S. (2017). Neurobiological bases of autism-epilepsy comorbidity: a focus on excitation/inhibition imbalance. Eur J Neurosci. Apr 27. doi: 10.1111/ejn.13595. [Epub ahead of print]
Zunino G., Messina A., Sgadò P., Baj G., Casarosa S., Bozzi Y. (2016). Brain-derived neurotrophic factor signaling is altered in the forebrain of Engrailed-2 knockout mice. Neuroscience 324:252-61. doi: 10.1016/j.neuroscience.2016.03.023. Epub 2016 Mar 14. I
Provenzano G., Sgadò P., Genovesi S., Zunino G., Casarosa S., Bozzi Y. (2015). Hippocampal dysregulation of FMRP/mGluR5 signaling in engrailed-2 knockout mice: a model of autism spectrum disorders. NeuroReport 26, 1101-1105.
Bertacchi M., Lupo G., Pandolfini L., Casarosa S., D’Onofrio M., Pedersen R.A., Harris W.A. and Cremisi F. (2015). Activin/Nodal Signaling Supports Retinal Progenitor Specification in a Narrow Time Window during Pluripotent Stem Cell Neuralization. Stem Cell Reports http://dx.doi.org/10.1016/j.stemcr.2015.08.011
Caputo A., Piano I., Demontis G.C., Bacchi N., Casarosa S., Della Santina L., Gargini C. (2015). TMEM16A is associated with voltage-gated calcium channels in mouse retina and its function is disrupted upon mutation of the auxiliary α2δ4 subunit. Front Cell Neurosci. 9:422. doi: 10.3389/fncel.2015.00422.
Bacchi N, Messina A, Burtscher V, Dassi E, Provenzano G, Bozzi Y, Demontis GC, Koschak A, Denti MA, Casarosa S. (2015). A New Splicing Isoform of Cacna2d4 Mimicking the Effects of c.2451insC Mutation in the Retina: Novel Molecular and Electrophysiological Insights. Invest Ophthalmol Vis Sci. 2015 Jul 1;56(8):4846-56. doi: 10.1167/iovs.15-16410.
Sun W., Incitti T., Migliaresi C., Quattrone A., Casarosa S., Motta A. (2015). Viability and neuronal differentiation of neural stem cells encapsulated in silk fibroin hydrogel functionalized with an IKVAV peptide. J Tissue Eng Regen Med. doi: 10.1002/term.2053.
Messina A., Lan L., Incitti T., Bozza A., Andreazzoli M., Vignali R., Cremisi F., Bozzi Y., Casarosa S. (2015). Noggin-Mediated Retinal Induction Reveals a Novel Interplay Between Bone Morphogenetic Protein Inhibition, Transforming Growth Factor β, and Sonic Hedgehog Signaling. Stem Cells 33(8):2496-508. doi: 10.1002/stem.2043.
Provenzano G., Pangrazzi L., Poli A., Sgadò P., Genovesi S., Zunino G., Berardi N., Casarosa S., Bozzi Y. (2014). Hippocampal dysregulation of neurofibromin-dependent pathways is associated with impaired spatial learning in Engrailed 2 knockout mice. Journal of Neuroscience, 34:13281-8. doi: 10.1523/JNEUROSCI.2894-13.2014 .
Bozza A., Coates E.E., Incitti T., Ferlin K., Messina A., Menna E., Bozzi Y., Fisher J.P., Casarosa S. (2014). Neural differentiation of pluripotent cells in 3D alginate-based cultures. Biomaterials 35: 4636-4645.
Sun W., Incitti T., Migliaresi C., Quattrone A., Casarosa S., Motta A. (2014). Genipin-crosslinked gelatin-silk fibroin hydrogels for modulating the behaviour of pluripotent cells. J Tissue Eng Regen Med. 2014 Jan 29. doi: 10.1002/term.1868. [Epub ahead of print].
Sgadò P., Genovesi S., Kalinowsky A., Zunino G., Macchi F., Allegra M., Murenu E., Provenzano G., Tripathi PP., Casarosa S., Joyner AL., Bozzi Y. (2013). Loss of GABAergic neurons in the hippocampus and cerebral cortex of Engrailed-2 null mutant mice: Implications for autism spectrum disorders. Exp Neurol. 247:496-505. doi: 10.1016/j.expneurol.2013.01.021. Epub 2013 Jan 27.
Bertacchi M., Pandolfini L., Murenu E., Viegi A., Capsoni S., Cellerino A., Messina A., Casarosa S., Cremisi F. (2013). The positional identity of mouse ES cells-generated neurons is affected by BMP signaling. Cell Mol Life Sci. 70:1095-111. doi: 10.1007/s00018-012-1182-3. Epub 2012 Oct 16.