No abstract

T-cell acute lymphoblastic leukemia (T-ALL) and lymphoma (T-LBL) share common morphological and immunophenotypic features and are treated with similar therapeutic approaches. Nonetheless, they show distinct clinical presentations, suggesting that they may represent two different biological entities. To investigate the genetic characteristics of T-LBL and T-ALL, we used genomic and transcriptional profiling approaches. Genome-wide gene expression profiling, performed on 20 T-LBL and 10 T-ALL diagnostic specimens, revealed that the two malignancies shared a large fraction of their transcriptional profile while a subset of genes appeared to be differentially expressed in T-LBL versus T-ALL. This signature included genes involved in chemotactic responses and angiogenesis, which may play a role in tumor cell localization. Genome-wide copy number alteration analysis was performed on a subset of the samples analyzed by gene expression profiling and detected 41 recurrently altered genetic loci. Although most aberrations were found in both entities, several were selectively identified in T-LBL or T-ALL. In addition, NOTCH1 mutational status was found to correlate with a subset of genetic aberrations. Taken together, these results suggest that T-LBL and T-ALL are indeed two distinct diseases with unique transcriptional and genetic characteristics.

In mammals, fertility critically depends on the pulsatile secretion of gonadotropin-releasing hormone (GnRH) by scattered hypothalamic neurons (GnRH neurons). During development, GnRH neurons originate in the nasal placode and migrate first into the nasal compartment and then through the nasal/forebrain junction, before they reach their final position in the hypothalamus. This neurodevelopmental process, which has been extensively studied in mouse models, is regulated by a plethora of factors that might control GnRH neuron migration or survival as well as the fasciculation/targeting of the olfactory/vomeronasal axons along which the GnRH neurons migrate. Defects in GnRH neuron development or release can lead to isolated GnRH deficiency, with the underlying genetic causes still being partially unknown. Recently, semaphorins and their receptors neuropilins and plexins, a large family of molecules implicated in neuronal development and plasticity, are emerging as key regulators of GnRH neuron biology and deficiency. Specifically, semaphorins have been shown to play different roles in GnRH neuron biology by regulating migration and survival during embryonic development as well as secretion in adulthood.

Neuronal migration is a fundamental biological process that underlies proper brain development and neuronal circuit formation. In the developing cerebral cortex, distinct neuronal populations, producing excitatory, inhibitory and modulatory neurotransmitters, are generated in different germinative areas and migrate along various routes to reach their final positions within the cortex. Different technical approaches and experimental models have been adopted to study the mechanisms regulating neuronal migration in the cortex. In this review, we will discuss the most common in vitro, ex vivo and in vivo techniques to visualize and study cortical neuronal migration.

Cornelia de Lange syndrome (CdLS) is a genetic disease that exemplifies the evolution of knowledge in the field of rare genetic disorders. Originally described as a unique pattern of major and minor anomalies, over time this syndrome has been shown to be characterized by a significant variability of clinical expression. By increasing the number of patients described, knowledge of the natural history of the condition has been enriched with the demonstration of the relative frequency of various potential comorbidities. Since 2006, the discovery of CdLS’s molecular basis has shown an equally vast genetic heterogeneity linked to the presence of variants in genes encoding for the cohesin complex pathway. The most recent clinical-genetic data led to the classification of the “original syndrome” into a “clinical spectrum” that foresees the presence of classic patients, of non-classic forms, and of conditions that show a modest phenotypic overlapping with the original disease. Finally, the knowledge of the molecular basis of the disease has allowed the development of basic research projects that could lay the foundations for the development of possible innovative pharmacological treatments.

No abstract

Protein kinase CK2 (CK2) is a highly conserved and ubiquitous kinase is involved in crucial biological processes, including proliferation, migration, and differentiation. CK2 holoenzyme is a tetramer composed by two catalytically active (α/α’) and two regulatory (β) subunits and exerts its function on a broad range of targets. In the brain, it regulates different steps of neurodevelopment, such as neural differentiation, neuritogenesis, and synaptic plasticity. Interestingly, CK2 mutations have been recently linked to neurodevelopmental disorders; however, the functional requirements of the individual CK2 subunits in neurodevelopment have not been yet investigated. Here, we disclose the role of CK2 on the migration and adhesion properties of GN11 cells, an established model of mouse immortalized neurons, by different in vitro experimental approaches. Specifically, the cellular requirement of this kinase has been assessed pharmacologically and genetically by exploiting CK2 inhibitors and by generating subunit-specific CK2 knockout GN11 cells (with a CRISPR/Cas9-based approach). We show that CK2α’ subunit has a primary role in increasing cell adhesion and reducing migration properties of GN11 cells by activating the Akt-GSK3β axis, whereas CK2α subunit is dispensable. Further, the knockout of the CK2β regulatory subunits counteracts cell migration, inducing dramatic alterations in the cytoskeleton not observed in CK2α’ knockout cells. Collectively taken, our data support the view that the individual subunits of CK2 play different roles in cell migration and adhesion properties of GN11 cells, supporting independent roles of the different subunits in these processes.

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