Migracija neurona tijekom razvoja telencefalona čovjeka

master's thesis

• Title (english): Neuronal migration during human telencephalon development
• Author: Lucija Raič
• Mentor: Goran Sedmak (mentor)
• Committee member: Željka Krsnik (predsjednik povjerenstva)
• Committee member: Zdravko Petanjek (član povjerenstva)
• Committee member: Goran Sedmak (član povjerenstva)
• Granter: University of Zagreb; School of Medicine; (Department of Physiology and Immunology); Zagreb
• Defense date and country: 2019-07-12, Croatia
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Basic Medical Sciences; Human Physiology
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Clinical Medical Sciences; Neurology

Abstract

Migracija neurona jedan je od ključnih procesa u formiranju funkcionalnog šesteroslojnog korteksa. Kreiranje djelotvorne moždane kore je složen postupak koji, osim neuralne migracije, uključuje neuralnu produkciju (simetričnom i asimetričnom diobom stanica) te modifikaciju neuronske mreže (sinaptogenezom i apoptozom). Lokalizacija i vrijeme proliferacije i migracije određuju identitet, poziciju unutar korteksa te povezanost svakog kortikalnog neurona. Ishodišno mjesto migracije su proliferativne zone razvojnog telencefalona – vetrikularna (VZ) i subventrikularna zona (SVZ), a odrediše je kortikalna ploča (CP). Neuroni koji potječu iz kortikalne VZ migriraju radijalno do CP i postaju projekcijski piramidni neuroni koji luče glutamat. Za razliku od njih, neuroni koji potječu iz razvojne osnove ganglijskih brežuljaka (MGE i LGE) migriraju tangencijalno te postaju interneuroni koji čine lokalne inhibitorne neuronske krugove te luče GABAu. Obje vrste neurona se smještaju u smjeru 'iznutra prema van', što znači da su ranije generirani neuroni smješteni u dubljim kortikalnim slojevima, a oni kasnije stvoreni u površnijim slojevima. Tokom migracije neuroni mijenjaju oblik kao i način, smjer i brzinu kretanja te gensku ekspresiju. Poremećaji bilo kojeg dijela ovog složenog procesa – bilo zbog mutacija gena, bilo zbog okolišnih utjecaja – dovesti će do malformacija kortikalnog razvoja, a danas znamo da su one jedan od vodećih uzroka mentalne retardacije i epilepsije refraktorne na farmakološko liječenje. Najčešći poremećaji kortikalnog razvoja su lizencefalija, periventrikularna heterotopija, fokalna kortikalna displazija i polimikrogirija. Sve nabrojane uzrok su teške invalidnosti, a istovremeno su terapijske mogućnosti izrazito skromne.

Abstract (english)

Neuronal migration has a key role in the formation of a functional six – layered cerebral cortex. Development of a functional cortex is a highly complicated process involving not only neuronal migration, but also neuronal production (via symmetric and asymmetric cell division) and modification of neuronal circuits (via synaptogenesis and apoptosis). The localization and timing of neuronal proliferation and neuronal migration define the identity, laminar positioning, and specific connectivity of each cortical neuron. Neurons start to migrate from their place of origin – proliferative zones of the developmental telencephalon (ventricular and subventricular zone), until they reach their final destination – the cortical plate. Neurons that originate from the cortical VZ migrate radially to the CP and mainly become glutamatergic projection neurons. In contrast, neurons derived from ganglionic eminences (MGE and LGE) migrate tangentially and give rise to GABAergic interneurons, which are incorporated into local neuronal circuits in the cerebral cortex. Both projection neurons and interneurons are located in 'inside – out' sequences in the cortical plate, that is, the early – born neurons are situated in the deep layers of the cortex, whereas the late – born neurons ultimately reside in the superficial layers. During migration, neurons change shape as well as mode, speed and direction of movement and gene expression. Alterations at any step of this process – due to mutations or environmental factors – lead to defined brain pathologies collectively known as malformations of brain development, which are now recognized as one of the leading causes of drug – resistant epilepsy and intellectual disability. Most common of those are lissencephaly, periventricular heterotopia, focal cortical dysplasia and polymicrogyria. All of them cause severe disabilities and at the same time treatment options are extremely modest.

• Keywords: neuroni; migracija neurona; korteks
• Keywords (english): neurons; neuronal migration; cortex
• Language: croatian
• URN:NBN: urn:nbn:hr:105:233420
• Study programme: Title: Medicine; Study programme type: university; Study level: integrated undergraduate and graduate; Academic / professional title: doktor/doktorica medicine (doktor/doktorica medicine)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Open access
• Created on: 2019-11-25 12:48:13