Dr. Giovanna Lalli’s research group, from left to right: Sangeetha Gajendra (Ph.D student), Zhou Ya (Ph.D student), Giovanna Lalli (PI), Kasia Falenta (post-doc) and Martina Sonego (Ph.D student).
Dr. Giovanna Lalli is a Lecturer in Molecular Neurobiology at the Wolfson Centre for Age-Related Diseases, King’s College London. Giovanna's research team is interested in the cytoskeletal and signalling mechanisms that regulate stem cell-derived neural progenitor migration and differentiation. As part of their research, the group regularly use the UltraVIEW® VoX 3D live cell imaging system.
The discovery of neurogenic stem cells niches in the adult mammalian brain has opened the exciting possibility of alternative therapeutic strategies in neurodegeneration. One of these niches is represented by the subventricular zone (SVZ). Neural progenitors originating from stem cells in the SVZ migrate through a stereotyped path, known as the rostral migratory stream (RMS), towards the olfactory bulb (OB) (Figure 1). Upon reaching the OB these neural progenitors disperse radially and integrate into pre-existing circuitry as inhibitory interneurons, ultimately modulating neuronal activity (Figure 2).
Importantly, several studies have highlighted the ability of SVZ-derived neuroblasts to migrate to areas affected by trauma or neurodegeneration. However, the molecular mechanisms underlying the control of their motility and their potential to differentiate into functional neurons have yet to be determined. SVZ-derived neuroblasts are an ideal model system for investigating the signalling pathways involved in migration and differentiation of stem cell-derived progenitors since they can be cultured and manipulated both in vitro and in vivo.
Figure 1: Mouse brain sagittal slice showing migrating neural progenitors five days after in vivo postnatal electroporation of a GFP-encoding plasmid in the SVZ.
Figure 2: Mouse olfactory bulb section showing inhibitory interneurons derived from neural progenitors fourteen days after electroporation of a GFP-encoding plasmid in the SVZ.
Researchers within Giovanna’s lab use a combination of biochemical and cell biological approaches to investigate the pathways involved in migration and differentiation of stem cell-derived progenitors. The team performs functional gene analysis in SVZ/RMS neural progenitors through in vivo postnatal electroporation of vectors for protein expression or shRNA-mediated depletion. For imaging the migration of neural progenitors in cultured brain slices, the team uses the UltraVIEW VoX 3D live cell imaging system (Movie).
Movie: Migration of GFP-labelled RMS neural progenitors towards the OB (located in the bottom right corner of the image) in a brain slice culture. The movie was acquired using the UltraVIEW VoX 3D live cell imaging system, and shows a projection of a stack of z-images covering about 100 µm in total. The sample was imaged every 3 min for a duration of ~150 min and the movie is played at 10 frames/second.
Giovanna says, “The UltraVIEW VoX system has added a new dimension to our research. For our previous studies we had to rely exclusively on fixed brain slices, however being able to observe neural progenitors in real time and to quantitatively analyze their motility using the Volocity software has made us understand much more about the regulation of their movement. The UltraVIEW VoX system and Volocity software have become an integral part of our daily life in the lab. We chose them because they are user-friendly, allow us to visualize and study our cells with reliability, and because of the great support PerkinElmer offers to their customers”.
Sonego M, Gajendra S, Parsons M, Ma Y, Hobbs C, Zentar MP, Williams G, Machesky LM, Doherty P and Lalli G (2013) Fascin Regulates the Migration of Subventricular Zone-Derived Neuroblasts in the Postnatal Brain. J. Neuroscience: 33 (30): 12171-12185.
Oudin M, Gajendra S, Williams G, Hobbs C, Lalli G and Doherty P (2011) Endocannabinoids regulate the migration of subventricular zone-derived neuroblasts in the postnatal brain. J Neurosci 31: 4000-4011.
Hall A and Lalli G (2010) Rho and Ras GTPases in axon growth, guidance, and branching. In ‘Wiring the brain: the biology of neuronal guidance'. M. Tessier-Lavigne and A. Kolodkin, editors. Cold Spring Harb Perspect Biol 2: a001818.
Lalli G (2009) RalA and the exocyst complex influence neuronal polarity through PAR-3 and aPKC. J Cell Sci 122: 1499-1506.
Giovanna obtained her MSc degree in Chemistry and Pharmaceutical Technology from the University of Bologna, Italy. She then moved to the University of Southern California, Los Angeles, USA, where she obtained an MSc degree in Molecular Biology. Giovanna carried out her PhD research at the Cancer Research UK London Research Institute, in Giampietro Schiavo’s laboratory, where she set up an assay based on the use of a tetanus toxin fragment to visualize axonal retrograde transport in living motor neurons. Giovanna then went on to perform post-doctoral research in Alan Hall’s group at the MRC Laboratory for Molecular and Cell Biology, University College London, investigating the role of small GTPase signalling in the regulation of neuronal morphology. In 2007 Giovanna was awarded a King’s College Young Investigator Fellowship, and was appointed to her current position as Lecturer in 2010.