Laminarni obrazac ekspresije i regionalna raspodjela RNA-vezujućeg proteina CELF1 u fetalnoj moždanoj kori čovjeka

doctoral thesis

• Title (english): Laminar expression pattern and regional distribution of RNA-binding protein CELF1 in the human fetal cerebral cortex
• Author: Janja Kopić
• Mentor: Željka Krsnik (mentor)
• Committee member: Ivica Kostović (predsjednik povjerenstva)
• Committee member: Mario Vukšić (član povjerenstva)
• Committee member: Nives Pećina-Šlaus (član povjerenstva)
• Committee member: Dubravka Švob Štrac (član povjerenstva)
• Committee member: Goran Šimić (član povjerenstva)
• Granter: University of Zagreb; School of Medicine; Zagreb
• Defense date and country: 2023-09-06, Croatia
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Basic Medical Sciences; Neuroscience
• Universal decimal classification (UDC): 611 - Anatomy

Abstract

Mozak predstavlja neurobiološki temelj svih funkcija kod čovjeka. Razvoj moždane kore karakterizira prostorno i vremensko preklapanje neurogenetskih procesa i regulacija genske ekspresije na nekoliko razina, među kojima je mRNA translacija, koordinirana putem RNA-vezujućih proteina. Celf1 je RNA-vezujući protein uključen u razvoj neuralnih progenitora i glutamatergičkih neurona tijekom kortikogeneze miša, a uloga CELF1 tijekom kortikogeneze čovjeka nije poznata. Hipoteza je da CELF1 regulira mRNA translaciju tijekom nastanka neuralnih progenitora te je njegova precizna regulacija nužna tijekom razvoja mozga čovjeka. Cilj je bio utvrditi laminarni i sublaminarni ekspresijski obrazac CELF1 te regionalne razlike na prenatalnom postmortalnom tkivu mozga čovjeka. CELF1 je eksprimiran u nezrelim neuronima VZ, SVZ i CP tijekom ranog te u postmigratornim neuronima CP i površnijeg dijela SP tijekom srednjeg fetalnog razdoblja. CELF1 ekspresijski obrazac pokazuje jasne regionalne citoarhitektonske razlike poput migratornih valova postmitotičkih neurona, obrazac „dvostruke CP“ u orbitobazalnom dijelu čeonog režnja, te specifične „corridor“ stanice u moždanoj kori zatiljnog režnja. Ekspresija u VZ, SVZ, i MACC, upućuje na ulogu CELF1 u diferencijaciji prospektivnih glutamategičkih projekcijskih piramidnih neurona, dok ekspresija u CP i SP upućuje na potencijalnu ulogu u molekularnoj specifikaciji, laminarnom pozicioniranju te uspostavljanju funkcionalne povezanosti. Stoga, istraživanje regulacije posttranskripcijskih mehanizama doprinosi boljem razumijevanju uzroka pojave neurorazvojnih poremećaja.

Abstract (english)

Human brain represents neurobiological basis of all functions. Cerebral cortex development is characterized by spatio-temporal overlapping of neurogenetic processes and gene expression regulation at several levels, including mRNA translation, coordinated by RNAbinding proteins. Celf1 is RNA-binding protein involved in neural progenitors and glutamatergic neurons development during mouse corticogenesis, but CELF1 role during human corticogenesis is unknown. The hypothesis is that CELF1 regulates mRNA translation during neural progenitors formation and its precise regulation is necessary during human corticogenesis. The aim was to determine laminar, sublaminar CELF1 expression pattern and regional differences in prenatal postmortem human brain tissue. CELF1 is expressed in immature neurons of VZ, SVZ and CP during early and in postmigratory neurons of CP and superficial part of SP during midfetal period. CELF1 expression pattern shows clear regional cytoarchitectonic differences such as postmitotic neurons migratory waves, "double CP" pattern in orbitobasal frontal cortex, and specific "corridor" cells in occipital cortex. Expression in VZ, SVZ, and MACC indicates CELF1 role in prospective glutamatergic projection pyramidal neurons differentiation, while expression in CP and SP indicates potential role in molecular specification, laminar positioning, and functional connectivity establishment. Therefore, investigating mechanisms of post-transcriptional regulation contributes to better understanding the origin of neurodevelopmental disorders.

• Keywords: Ljudi; Životinje; Miševi; CELF1 Protein; Prospektivne studije; Neuroni; Regulacija ekspresije gena; Mozak; Piramidalne stanice
• Keywords (english): Humans; Animals; Mice; CELF1 Protein; Prospective Studies; Neurons; Gene Expression Regulation; Brain; Pyramidal Cells
• Language: croatian
• URN:NBN: urn:nbn:hr:105:103299
• Project: Number: PZS-2019-02-4710; Title: Uloga RNA vezujućeg proteina CELF 1 u neuronalnom razvoju čovjeka; Title: Role of RNA binding protein CELF1 in normal and abnormal human neuronal development; Acronym: CELF1NeuDev; Leader: Željka Krsnik; Jurisdiction: Croatia; Funder: HRZZ; Funding stream: Nema
• Project: Number: KK.01.1.1.01.0007; Title: Eksperimentalna i klinička istraživanja hipoksijsko-ishemijskog oštećenja mozga u perinatalnoj i odrasloj dobi; Leader: Miloš Judaš; Jurisdiction: Croatia; Funder: EK
• Study programme: Title: Neuroscience; Study programme type: university; Study level: postgraduate; Academic / professional title: doktor/doktorica znanosti, područje biomedicine i zdravstvo (doktor/doktorica znanosti, područje biomedicine i zdravstvo)
• Type of resource: Text
• Extent: 127 str.
• File origin: Born digital
• Access conditions: Open access
• Created on: 2023-09-14 09:20:40