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Proc Natl Acad Sci U S A 2024 Jan 16;1213:e2316542121. doi: 10.1073/pnas.2316542121.
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BRCA1 and ELK-1 regulate neural progenitor cell fate in the optic tectum in response to visual experience in Xenopus laevis tadpoles.

Huang LC , McKeown CR , He HY , Ta AC , Cline HT .

In developing Xenopus tadpoles, the optic tectum begins to receive patterned visual input while visuomotor circuits are still undergoing neurogenesis and circuit assembly. This visual input regulates neural progenitor cell fate decisions such that maintaining tadpoles in the dark increases proliferation, expanding the progenitor pool, while visual stimulation promotes neuronal differentiation. To identify regulators of activity-dependent neural progenitor cell fate, we profiled the transcriptomes of proliferating neural progenitor cells and newly differentiated neurons using RNA-Seq. We used advanced bioinformatic analysis of 1,130 differentially expressed transcripts to identify six differentially regulated transcriptional regulators, including Breast Cancer 1 (BRCA1) and the ETS-family transcription factor, ELK-1, which are predicted to regulate the majority of the other differentially expressed transcripts. BRCA1 is known for its role in cancers, but relatively little is known about its potential role in regulating neural progenitor cell fate. ELK-1 is a multifunctional transcription factor which regulates immediate early gene expression. We investigated the potential functions of BRCA1 and ELK-1 in activity-regulated neurogenesis in the tadpole visual system using in vivo time-lapse imaging to monitor the fate of GFP-expressing SOX2+ neural progenitor cells in the optic tectum. Our longitudinal in vivo imaging analysis showed that knockdown of either BRCA1 or ELK-1 altered the fates of neural progenitor cells and furthermore that the effects of visual experience on neurogenesis depend on BRCA1 and ELK-1 expression. These studies provide insight into the potential mechanisms by which neural activity affects neural progenitor cell fate.

PubMed ID: 38198524
PMC ID: PMC10801852
Article link: Proc Natl Acad Sci U S A
Grant support: [+]

Species referenced: Xenopus laevis
Genes referenced: abl2 acta2 aurkb bmp4 brca1 cacul1 cdc14a cdc14b cdc45 cebpb dbf4b dnah10 dnah11 e4f1 elk1 fgf11 fgf2 fosl1 fscn2 gsg1l hdac7 hdac9 jak2 lats2 mad2l1 mnat1 mos mycl neurod1 nfkb1 nr2f5 orc6 pdgfa phc3 pim1 pkmyt1 plk2 prc1 prkacb rapgef4 rcc1 recql rxrb samd13 septin2 sertad2 smad9 sox2 sstr4 sstr5 tecta tgfa togaram2 ttc29 ube2c vegfa wnt1
GO keywords: brain development [+]
Antibodies: Brca1 Ab1 Elk1 Ab1 H3f3a Ab45 Sox2 Ab12
Morpholinos: brca1 MO4 elk1 MO2 sox2 MO2

Article Images: [+] show captions
References [+] :
Aizenman, Enhanced visual activity in vivo forms nascent synapses in the developing retinotectal projection. 2007, Pubmed, Xenbase