Ongoing projects

Four main projects are currently ongoing in the SISSA Laboratory of Cerebral Cortex Development.

Modelling etiopathogenesis of the Foxg1-linked variant of West syndrome

West syndrome (WS)  is a devastating pathological condition occurring in circa 1 every 3,500 infants. It includes infantile-onset spasms, prominent interictal EEG abnormalities and impaired psychomotor development. Spasms and EEG abnormalities often disappear before 3 years of age. However, the majority of patients will develop other types of epileptic syndromes. WS etiopathogenesis is extremely complex. A subset of WS cases is linked to defined gene lesions. In particular, in up to 5% of cases, WS has been associated to 14q12 microduplications including the transcription factor gene FOXG1.

Genetic control of cortico-cerebral astrogenesis

Astrocytes play a large variety of roles in cortico-cerebral development, physiology and pathology. They shape the morphology of neuronal dendrites and assist migration of some neuronal progenitors. They contribute to genesis and function of the blood-brain barrier, provide structural and metabolic support to neurons and modulate synaptic transmission and information processing.

RNA-therapeutics of gene haploinsufficiencies

Defective gene expression has being recognized as the main causative agent or a key factor risk of a number of rare diseases,among which several ones affecting the central nervous system (CNS). It may be due to chromosomal microdeletions, spanning one or a few contiguous genes. Alternatively, the number of alleles may be correct, however these alleles may be poorly expressed, because of anomalous cis-active signals modulating transcription, intrinsic mRNA instability and/or poor translatability. 

Gene therapy of glioblastoma

Glioblastoma is a highly heterogenous and devastating CNS tumour for which no cure is presently available. The brain patterning gene Emx2 normally inhibits proliferation of astrocyte progenitors. Moreover, it is poorly expressed by human glioblastomas compared to surrounding healthy tissue. Interestingly, we found that Emx2 overexpression induced the collapse of nine out of nine in vitro tested glioblastoma cell lines, antagonizing their proliferation and stimulating apoptosis.