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Development 2013 Aug 01;14015:3095-106. doi: 10.1242/dev.093716.
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ERF and ETV3L are retinoic acid-inducible repressors required for primary neurogenesis.

Janesick A , Abbey R , Chung C , Liu S , Taketani M , Blumberg B .

Cells in the developing neural tissue demonstrate an exquisite balance between proliferation and differentiation. Retinoic acid (RA) is required for neuronal differentiation by promoting expression of proneural and neurogenic genes. We show that RA acts early in the neurogenic pathway by inhibiting expression of neural progenitor markers Geminin and Foxd4l1, thereby promoting differentiation. Our screen for RA target genes in early Xenopus development identified Ets2 Repressor Factor (Erf) and the closely related ETS repressors Etv3 and Etv3-like (Etv3l). Erf and Etv3l are RA responsive and inhibit the action of ETS genes downstream of FGF signaling, placing them at the intersection of RA and growth factor signaling. We hypothesized that RA regulates primary neurogenesis by inducing Erf and Etv3l to antagonize proliferative signals. Loss-of-function analysis showed that Erf and Etv3l are required to inhibit proliferation of neural progenitors to allow differentiation, whereas overexpression of Erf led to an increase in the number of primary neurons. Therefore, these RA-induced ETS repressors are key components of the proliferation-differentiation switch during primary neurogenesis in vivo.

PubMed ID: 23824578
Article link: Development

Species referenced: Xenopus laevis
Genes referenced: aldh1a2 aqp3 cyp26a1 ddx20 dll1 erf ets2 etv3 etv3l foxd4l1.1 gmnn h3-3a hoxa1 myt1 neo1 neurog2 pcna psmd6 rab40b rara rarg sox2 sox3 tubb2b zic1 zic2 zic3
Morpholinos: aldh1a2 MO3 cyp26a1 MO1 erf MO1 erf MO2 etv3 MO1 etv3l MO1 rara MO1 rara MO2 rara MO3 rara MO5 rara MO6 rarg MO1 rarg MO2

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