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Stage-specific roles of FGF2 signaling in human neural development

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GRABIEC Marta HŘÍBKOVÁ Hana VAŘECHA Miroslav STŘÍTECKÁ Dana HAMPL Aleš DVOŘÁK Petr SUN Yuh-Man

Rok publikování 2016
Druh Článek v odborném periodiku
Časopis / Zdroj Stem Cell Research
Fakulta / Pracoviště MU

Lékařská fakulta

Citace
Doi http://dx.doi.org/10.1016/j.scr.2016.08.012
Obor Genetika a molekulární biologie
Klíčová slova Neural developmental modeling; Embryonic stem cells; Neural fate; Neurogenesis; FGF2 signaling; Neural stem cell niche
Popis This study elucidated the stage-specific roles of FGF2 signaling during neural development using in-vitro human embryonic stem cell-based developmental modeling. We found that the dysregulation of FGF2 signaling prior to the onset of neural induction resulted in the malformation of neural rosettes (a neural tube-like structure), despite cells having undergone neural induction. The aberrant neural rosette formation may be attributed to the misplacement of ZO-1, which is a polarized tight junction protein and shown co-localized with FGF2/FGFR1 in the apical region of neural rosettes, subsequently led to abnormal neurogenesis. Moreover, the FGF2 signaling inhibition at the stage of neural rosettes caused a reduction in cell proliferation, an increase in numbers of cells with cell-cycle exit, and premature neurogenesis. These effects may be mediated by NUMB, to which expression was observed enriched in the apical region of neural rosettes after FGF2 signaling inhibition coinciding with the disappearance of PAX6+/Ki67+ neural stem cells and the emergence of MAP2+ neurons. Moreover, our results suggested that the hESC-based developmental system reserved a similar neural stem cell niche in vivo.
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