Abstract:
: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.
journal_name
Stem Cell Resjournal_title
Stem cell researchauthors
Grabiec M,Hříbková H,Vařecha M,Střítecká D,Hampl A,Dvořák P,Sun YMdoi
10.1016/j.scr.2016.08.012subject
Has Abstractpub_date
2016-09-01 00:00:00pages
330-341issue
2eissn
1873-5061issn
1876-7753pii
S1873-5061(16)30111-8journal_volume
17pub_type
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