Naslov
Transcription factor CUX2 and post-transcriptional factor CELF4 in neurons of synapse-enriched layers during human fetal corticogenesis

Autori
Miškić, Terezija

Vrsta, podvrsta i kategorija rada
Ocjenski radovi, doktorska disertacija

Fakultet
Medicinski fakultet

Mjesto
Zagreb

Datum
03.01

Godina
2022

Stranica
103

Mentor
Krsnik, Željka ; Rašin, Mladen-Roko

Ključne riječi
neurons, synapses, RNA, fetal development, frontal lobe

Sažetak
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.

Izvorni jezik
Engleski

Znanstvena područja
Temeljne medicinske znanosti

POVEZANOST RADA