prikaz prve stranice dokumenta Transcription factor CUX2 and post-transcriptional factor CELF4 in neurons of synapse-enriched layers during human fetal corticogenesis
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doctoral thesis
Transcription factor CUX2 and post-transcriptional factor CELF4 in neurons of synapse-enriched layers during human fetal corticogenesis
Zagreb: University of Zagreb, School of Medicine, 2022. urn:nbn:hr:105:843366
Miškić, Terezija
University of Zagreb
School of Medicine

Institutional repository: Dr Med - University of Zagreb School of Medicine Digital Repository

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Miškić, T. (2022). Transcription factor CUX2 and post-transcriptional factor CELF4 in neurons of synapse-enriched layers during human fetal corticogenesis (Doctoral thesis). Zagreb: University of Zagreb, School of Medicine. Retrieved from https://urn.nsk.hr/urn:nbn:hr:105:843366

Miškić, Terezija. "Transcription factor CUX2 and post-transcriptional factor CELF4 in neurons of synapse-enriched layers during human fetal corticogenesis." Doctoral thesis, University of Zagreb, School of Medicine, 2022. https://urn.nsk.hr/urn:nbn:hr:105:843366

Miškić, Terezija. "Transcription factor CUX2 and post-transcriptional factor CELF4 in neurons of synapse-enriched layers during human fetal corticogenesis." Doctoral thesis, University of Zagreb, School of Medicine, 2022. https://urn.nsk.hr/urn:nbn:hr:105:843366

Miškić, T. (2022). 'Transcription factor CUX2 and post-transcriptional factor CELF4 in neurons of synapse-enriched layers during human fetal corticogenesis', Doctoral thesis, University of Zagreb, School of Medicine, accessed 25 November 2024, https://urn.nsk.hr/urn:nbn:hr:105:843366

Miškić T. Transcription factor CUX2 and post-transcriptional factor CELF4 in neurons of synapse-enriched layers during human fetal corticogenesis [Doctoral thesis]. Zagreb: University of Zagreb, School of Medicine; 2022 [cited 2024 November 25] Available at: https://urn.nsk.hr/urn:nbn:hr:105:843366

T. Miškić, "Transcription factor CUX2 and post-transcriptional factor CELF4 in neurons of synapse-enriched layers during human fetal corticogenesis", Doctoral thesis, University of Zagreb, School of Medicine, Zagreb, 2022. Available at: https://urn.nsk.hr/urn:nbn:hr:105:843366

Metadata
TitleTranscription factor CUX2 and post-transcriptional factor CELF4 in neurons of synapse-enriched layers during human fetal corticogenesis
Title (english)Transcription factor CUX2 and post-transcriptional factor CELF4 in neurons of synapse-enriched layers during human fetal corticogenesis
AuthorTerezija Miškić
MentorŽeljka Krsnik (mentor)
Committee memberIvica Kostović (predsjednik povjerenstva)
Committee memberGoran Šimić (član povjerenstva)
Committee memberMario Vukšić (član povjerenstva)
Committee memberDubravka Švob Štrac (član povjerenstva)
Committee memberNives Pećina-Šlaus (član povjerenstva)
GranterUniversity of Zagreb
School of Medicine
Zagreb
Defense date and country2022-01-05, Croatia
Scientific / art field,
discipline and subdiscipline		BIOMEDICINE AND HEALTHCARE
Basic Medical Sciences
Neuroscience
Universal decimal classification
(UDC)		61 - Medical sciences
Abstract
Cortical development of the human fetus is a protracted process filled with critical histogenetic events which give rise to the brain complexities differentiating in the transient neocortical compartments. Transcriptional and post-transcriptional mechanisms are the fundament of neurogenetic and histogenetic events, with the transcription and post-transcriptional factors acting as crucial impactors of neural development. In this thesis, spatio-temporal dynamics of CUX2 transcription factor and post-transcriptional factor, CELF4, in human fetal development are studied in depth. To explore their role in cortical development, human post-mortem fetal tissue from 8 PCW to 38 PCW, in addition to adult tissue was used for the experiments. The results show CUX2 nuclear expression in neurons of the transient compartments from 8 PCW to 38 PCW of the human fetal prospective frontal cortex, specifically in the CR cells of the MZ and in the neurons of the SP zone. Both CUX2 and CELF4 are expressed in the migratory cells, projection neuronal subpopulation, and in the subpopulation of interneurons. CELF4 positive neurons were found in the synaptophysin-immunoreactive synaptic strata during midgestation. We have also identified human early and midfetal mRNA binding targets of CELF4: TLE4, EIF4A2, VGLUT1, and SYNPR. In conclusion, CUX2 participates in the molecular specification, circuit formation, and synaptogenesis of fetal transient SP and MZ projection neurons as it does in permanent projection neurons of upper layers. CELF4 attains a role in cortical development, by regulating mRNAs involved in the processes of transcription regulation, axonal pathfinding, and synapse formation. The results of this thesis show the spatio-temporal expression pattern of TF, CUX2, and RBP, CELF4 in correlation with the dynamics of cortical processes taking place in the same laminae, which indicates their important roles in the differentiation of the cortex.
Abstract (english)
Razvoj moždane kore fetusa čovjeka je kompleksan proces, ispunjen ključnim histogenetskim zbivanjima koji se ostvaraju u prolaznim fetalnim zonama, a čiji učinci se vide u konačnoj složenosti funkcija ljudskoga mozga. Transkripcijski i post-transkripcijski mehanizmi su u pozadini neurogenetskih i histogenetskih događaja, te imaju izravan utjecaj na razvoj mozga. Tema ovog doktorskog istraživanja je analiza vremensko-prostornog obrasca ekspresije transkripcijskog faktora CUX2 i post-transkripcijskog faktora CELF4 tijekom fetalnog razvoja ljudskog mozga. Da bi istražili njihovu ulogu u razvoju moždane kore, korišteni su postmortalni uzorci mozga starosti od 8 PCW do 38 PCW, te dodatno uzorci odraslog mozga. Rezultati ovog istraživanja pokazuju da je CUX2 eksprimiran u jezgrama neurona prolaznih fetalnih zona u dobi od 8 do 38 PCW moždane kore čeonog režnja, a posebno unutar jezgara CR stanica marginalne zone (MZ) i neurona subplate (SP) zone. CUX2 i CELF4 su eksprimirani u migratornim stanicama, projekcijskim neuronima i u interneuronima moždane kore. CELF4 pozitivni neuroni su pronađeni unutar sinaptičkih slojeva koji su imunoreaktivni na sinaptofizin, tijekom midgestacije. Tijekom ranog i srednjeg fetalnog razdbolja CELF4 veže mRNA TLE4, EIF4A2, VGLUT1 i SYNPR. Zaključno, CUX2 sudjeluje u procesima molekularne specifikacije, organizacije neuralnih veza, i sinaptogeneze u fetalnim prolaznim MZ i SP projekcijskim neuronima, te u stalnim projekcijskim neuronima površnih slojeva moždane kore. Uloga CELF4 proteina u razvoju moždane kore je u regulaciji mRNA uključenih u procese regulacije transkripcije, navođenja aksona i formacije sinapsi. Rezultati ove disertacije prikazuju vremensko-prostorni ekspresijski obrazac transkripcijskog faktora CUX2 i RNA-vezujućeg proteina CELF4 u korelaciji sa dinamikom zbivanja u moždanoj kori koji se događaju u isto vrijeme u istim slojevima, te time odražavaju njihovu ulogu u diferencijaciji moždane kore.
Keywords
Keywords (english)
Languageenglish
URN:NBNurn:nbn:hr:105:843366
ProjectNumber: KK.01.1.1.01.0007
Title: Eksperimentalna i klinička istraživanja hipoksijsko-ishemijskog oštećenja mozga u perinatalnoj i odrasloj dobi
Leader: Ivica Kostović
Jurisdiction: eu
Funder: EK
Study programmeTitle: Neuroscience
Study programme type: university
Study level: postgraduate
Academic / professional title: doktor/doktorica znanosti, područje biomedicine i zdravstva (doktor/doktorica znanosti, područje biomedicine i zdravstva)
Type of resourceText
Extent103 str.
File originBorn digital
Access conditionsOpen access
Embargo expiration date: 2023-05-05
Terms of useLicence In copyright icon
Public noteSumentor: Mladen-Roko Rašin
Created on2022-03-31 08:43:05