engleski

The semaphorin5a developmental expression and functional role in mice telencephalon

The Semaphorin-5A (Sema5A) is a transmembrane protein that has been shown to have a role as bifunctional guidance molecule during axon elongation and cell migration in the development of diencephalon and its connections. Mutations of Sema5A are linked to the etiology of several disorders and syndromes, such as microdeletion of SEMA5A found in patients with autism spectrum and haploinsufficiency for SEMA5A in Cri-du-chat syndrome. We are lacking data on SEMA5A protein expression in human brain but according to the recent data (Allan Brain Institute), the transcripts of Sema5A gene are present in proliferative zones of the developing telencephalon in rodents at E13.5 E15.5 and P14. In this study, in vitro functional essay and postmortem protein expression analysis were used to reveal the role of Sema5A in brain development in mice. Results show that Sema5A promotes outgrowth and elongation of neocortical axons when uniformly surround immature cortical neurons, but does not steer axons or modulate collateralization. The expression of Sema5A protein was more prominent at P15 than at P5 in the entire cortex with the clear regional differences in the expression with the most prominent expression observed in somatosensory cortex ar P15. Further studies of Sema5A in coexpression with specific proteoglycans of extracellular matrix are needed to get a better understanding of the Sema5A role in the development of the telencephalon connectivity in health and disease. The study was co-financed by the European Union through the European Regional Development Fund, Operational Programme Competitiveness, and Cohesion, grant agreement No. KK.01.1.1.01.0007, CoRE and Croatian Science Foundation.

cortex ; axon guidance ; thrombospondin repeats ; autism spectrum disorder

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