Early Regional Patterning in the Human Prefrontal Cortex Revealed by Laminar Dynamics of Deep Projection Neuron Markers

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• Autor: Janja Kopić
• Autor: Alisa Junaković
• Autor: Iva Salamon
• Autor: Mladen-Roko Rasin
• Autor: Ivica Kostović
• Autor: Željka Krsnik
• Autorova ustanova: Sveučilište u Zagrebu; Medicinski fakultet; (HRVATSKI INSTITUT ZA ISTRAŽIVANJE MOZGA)
• Znanstveno / umjetničko područje, polje i grana: BIOMEDICINA I ZDRAVSTVO; Temeljne medicinske znanosti; Neuroznanost

Sažetak (engleski)

Early regional patterning and laminar position of cortical projection neurons is determined by activation and deactivation of transcriptional factors (TFs) and RNA binding proteins (RBPs) that regulate spatiotemporal framework of neurogenetic processes (proliferation, migration, aggregation, postmigratory differentiation, molecular identity acquisition, axonal growth, dendritic development, and synaptogenesis) within transient cellular compartments. Deep-layer projection neurons (DPN), subplate (SPN), and Cajal–Retzius neurons (CRN) are early-born cells involved in the establishment of basic laminar and regional cortical architecture; nonetheless, laminar dynamics of their molecular transcriptional markers remain underexplored. Here we aimed to analyze laminar dynamics of DPN markers, i.e., transcription factors TBR1, CTIP2, TLE4, SOX5, and RBP CELF1 on histological serial sections of the human frontal cortex between 7.5–15 postconceptional weeks (PCW) in reference to transient proliferative, migratory, and postmigratory compartments. The subtle signs of regional patterning were seen during the late preplate phase in the pattern of sublaminar organization of TBR1+/Reelin+ CRN and TBR1+ pioneering SPN. During the cortical plate (CP)-formation phase, TBR1+ neurons became radially aligned, forming continuity from a well-developed subventricular zone to CP showing clear lateral to medial regional gradients. The most prominent regional patterning was seen during the subplate formation phase (around 13 PCW) when a unique feature of the orbitobasal frontal cortex displays a “double plate” pattern. In other portions of the frontal cortex (lateral, dorsal, medial) deep portion of CP becomes loose and composed of TBR1+, CTIP2+, TLE4+, and CELF1+ neurons of layer six and later-born SPN, which later become constituents of the expanded SP (around 15 PCW). Overall, TFs and RBPs mark characteristic regional laminar dynamics of DPN, SPN, and CRN subpopulations during remarkably early fetal phases of the highly ordered association cortex development.

• Ključne riječi (engleski): Cerebral Cortex / metabolism; Frontal Lobe / metabolism; Humans; Neurons / metabolism; Prefrontal Cortex / metabolism; Transcription Factors / metabolism
• Jezik: engleski
• Vrsta publikacije: Znanstveni rad - Izvorni znanstveni rad
• Status objave: Objavljen
• Vrsta recenzije: Recenziran
• Verzija publikacije: Objavljena verzija rada (izdavačev PDF)
• Naslov časopisa: Cells
• Brojčani podaci: vol. 12, br. 2, 231
• e-ISSN: 2073-4409
• DOI: https://doi.org/10.3390/cells12020231
• URN:NBN: urn:nbn:hr:105:262644
• Datum objave publikacije: 2023-01-05
• Projekt: Šifra: PZS-2019-02-4710; Naziv (hrvatski): Uloga RNA vezujućeg proteina CELF 1 u neuronalnom razvoju čovjeka; Naziv (engleski): Role of RNA binding protein CELF1 in normal and abnormal human neuronal development; Kratica: CELF1NeuDev; Voditelj: Željka Krsnik; Pravna nadležnost: Hrvatska; Financijer: HRZZ; Linija financiranja: Nema
• Projekt: Šifra: KK.01.1.1.01.0007; Naziv (engleski): Eksperimentalna i klinička istraživanja hipoksijsko-ishemijskog oštećenja mozga u perinatalnoj i odrasloj dobi; Voditelj: Ivica Kostović; Pravna nadležnost: eu; Financijer: EK
• URL dokumenta: https://www.mdpi.com/2073-4409/12/2/231
• Vrsta resursa: Tekst
• Prava pristupa: Otvoreni pristup
• Datum i vrijeme pohrane: 2024-02-15 10:20:58