Paolo Forni

Forni Lab Website

Areas of Interest

• Cell populations and their development in the olfactory system.
• Normal and pathological development of the olfactory and GnRH-1 system.
• Genes and molecular mechanisms of placodal/neural crest interactions, and determinants of neurogenic niches.

Research

Correct development of the nose is necessary for detection of environmental odorants but is also crucial for maturation and function of the reproductive system. In fact, during embryonic development a population of neurons, called gonadotropin-releasing hormone-1 neurons (GnRH-1), migrate from the nose to the brain. Once in the brain, these neurons control the reproductive axis. Genetic defects that affect the formation of the nasal/olfactory structures, as well as migration, survival and/or function of GnRH-1 neurons lead to aberrant sexual development and sterility. Our understanding of who are the stem cells and what is the embryonic origin in the developing nose has only recently began, which leaves many blanks yet to be filled.

Formation of the nose is the result of communication and interaction of contributing cells of different embryonic origin, in particular placodal cells (which form most of the olfactory/vomeronasal epithelium) and neural crest cells (which give rise to bones, cartilage and olfactory glia cells). Defects in craniofacial development, olfaction and sexual development have been linked in a growing number of human syndromes.

Our lab is interested in unravelling:

1. What are the different cell populations in the nasal area, and what is their role during embryonic development?
2. What is the role played by different cell types in normal and pathological development of the olfactory and GnRH-1 system?
3. Which genes are involved, and what are the molecular mechanisms at the base of placodal/neural crest interaction and the determination of neurogenic niches?

Our investigative approach is based on in vivo and ex-vivo observations using mouse lines carrying genetic mutations that mimic human developmental pathologies as well as animal models that allow us to selectively trace or genetically manipulate specific cells types.

Publications

• Taroc E.Z.M., Kathreddi R., Forni P.E. (2020).  Identifying Isl1 genetic lineage in the developing olfactory system and in GnRH-1 neurons.  Frontiers in Physiology. In Press
• Naik A. S., Lin J. M., Taroc E. Z. M., Katreddi R. R., Frias J. A., Lemus A. A., Sammons M.A, Forni P. E. (2020). Smad4-dependent morphogenic signals control the maturation and axonal targeting of basal vomeronasal sensory neurons to the accessory olfactory bulb. Development. 147(8): dev184036. 
• Rosinger Z., De Guzman R., Jacobskind J., Saglimbeni B., Malone M., Fico D., Justice N, Forni P.E., Zuloaga DG. (2020).  Sex-dependent effects of chronic variable stress on discrete corticotropin-releasing factor receptor 1 cell populations. Physiol Behav. 219:112847.
• Taroc E.Z.M., Lin J.M., Naik A., Peterson N.B., Genis E., Fuchs.G., Keefe D., Balasubramanian R., Forni P.E. (2020). Gli3 Loss-of-Function Mutations cause defective GnRH-1 neuronal migration to the brain. JNeurosci, ++Cover Article  
• Taroc EZM, Lin JN, Tulloch AJ, Jaworski A, Forni P.E. (2019). GnRH-1 neural migration from the nose to the brain is independent from Slit2, Robo3 and NELL2 signaling. Frontiers Cellular Neuroscience, 2019; 13:146.
• Lin JN, Taroc EZM, Frias JA, Prasad A, Catizone AN, Sammons MA, Forni P.E. (2018). The transcription factor Tfap2e/AP-2ε plays a pivotal role in maintaining the identity of basal vomeronasal sensory neurons. Developmental biology; 441(1):67-82. 
• Taroc E.Z.M., Prasad A, Lin J.M, Forni P.E. (2017). The terminal nerve plays a prominent role in GnRH-1 neuronal migration independent from proper olfactory and vomeronasal connections to the olfactory bulbs. Biology Open;6 (10):1552-68.  **Highlighted as article of special significance in its field in F1000.
• Morena D., Maestro N., Bersani F., Forni P.E., Lingua M.F., Foglizzo V., Šćepanović P., Miretti S., Morotti A., Shern J.F., Khan J., Ala U., Provero P., Sala V., Crepaldi T., Gasparini P., Casanova M., Ferrari A., Sozzi G., Chiarle R., Ponzetto C., Taulli R. (2016). Hepatocyte Growth Factor-mediated satellite cells niche perturbation promotes development of distinct sarcoma subtypes. e-Life. 12116.
• Forni PE and Wray S (2015). GnRH, anosmia and hypogonadotropic hypogonadism - where are we? Frontiers in Neuroendocrinoogy. 36:165-177
• Forni PE, Bharti K, Flannery EM, Shimogori T, Wray S (2013). The indirect role of FGF8 in defining neurogenic niches of the olfactory/GnRH systems. J.Neurosci. 33:19620-19634 ++Cover Picture
• Forni PE and Wray S (2012). Neural Crest and olfactory system: new prospective. Molecular Neurobiology. 2012 Oct;46:349-60
• Forni PE, Taylor-Burds C, Senkus Melvin V, Williams T, Wray S (2011). Neural crest and Ectodermal cells intermix in the nasal placode to give rise to GnRH-1 Neurons, Sensory Neurons and Olfactory Ensheathing Cells. J.Neurosci. 31:13023.        ++Cover Picture
• Forni  PE, Fornaro M, Guénette S, Wray S (2011). A role for FE65 in controllingGnRH-1 neurogenesis. J. Neurosci. 31:480-91
• Voyron S, Rocco F, Ceruti M, Forni PE, Pla AF, Sarpietro MG, Varese GC,  Marchisio VF (2009). Antifungal activity of bis-azasqualenes, inhibitors of  oxidosqualene cyclase. Mycoses. 53:481-7
• Accornero P, Lattanzio G, Mangano T, Chiarle R, Taulli R, Bersani F, Forni PE, Miretti S, Scuoppo C, Dastrù W, X, Christensen JG , Crepaldi  T and Ponzetto C (2008). An in vivo Model of Met-driven Lymphoma as a Tool to Explore the Therapeutic Potential of Met Inhibitors. Clin Cancer Res.14:2220-6. 
• Crepaldi T, Bersani F, Scuoppo C, Accornero P, Prunotto C, Taulli R, Forni PE, Leo C, Chiarle R, Griffiths J, Glass DJ, Ponzetto C (2007) Conditional activation of MET in differentiated skeletal muscle induces atrophy. J Biol Chem 282:6812-6822.
• Scuoppo C, Riess I, Schmitt-Ney M, Allegra P, Forni PE, Bersani F, Taulli R, Accornero P, Crepaldi T, Ponzetto C (2007) The oncogenic transcription factor PAX3-FKHR can convert fibroblasts into contractile myotubes. Exp Cell Res 31:2308-17.
• Taulli R, Scuoppo C, Bersani F, Accornero P, Forni PE, Miretti S, Grinza A, Allegra P, Schmitt-Ney M, Crepaldi T, Ponzetto C (2006) Validation of met as a therapeutic target in alveolar and embryonal rhabdomyosarcoma. Cancer Res 66:4742-4749.
• Forni PE, Scuoppo C, Imayoshi I, Taulli R, Dastru W, Sala V, Betz UA, Muzzi P, Martinuzzi D, Vercelli AE, Kageyama R, Ponzetto C (2006) High levels of Cre expression in neuronal progenitors cause defects in brain development leading to microencephaly and hydrocephaly. J Neurosci 26:9593-9602.
• Taulli R, Accornero P, Follenzi A, Mangano T, Morotti A, Scuoppo C, Forni PE, Bersani F, Crepaldi T, Chiarle R, Naldini L, Ponzetto C (2005)RNAi technology and lentiviral delivery as a powerful tool to suppress Tpr-Met-mediated tumorigenesis. Cancer Gene Ther 12:456-463.
• Forni PE*, Prunotto C*, Crepaldi T*, Ieraci A, Kelly RG, Tajbakhsh S, Buckingham M, Ponzetto C (2004) Analysis of Mlc-lacZ Met mutants highlights the essential function of Met for migratory precursors of hypaxial muscles and reveals a role for Met in the development of hyoid arch-derived facial muscles. Dev Dyn 231:582-591. *Equal contribution              ++Cover Picture
• Forni PE*, Ieraci A*, Ponzetto C (2002) Viable hypomorphic signaling mutant of the Met receptor reveals a role for hepatocyte growth factor in postnatal cerebellar development. Proc Natl Acad Sci U S A 99:15200-15205. * Equal contribution
• Baldelli P, Forni PE, Carbone E (2000) BDNF, NT-3 and NGF induce distinct new Ca2+ channel synthesis in developing hippocampal neurons. Eur J Neurosci 12:4017-4032.