An Evolutionarily Conserved SoxB-Hdac2 Crosstalk Regulates Neurogenesis in a Cnidarian

Publication date: 7 February 2017
Source:Cell Reports, Volume 18, Issue 6
Author(s): Hakima Flici, Christine E. Schnitzler, R. Cathriona Millane, Graham Govinden, Amy Houlihan, Stephanie D. Boomkamp, Sanbing Shen, Andreas D. Baxevanis, Uri Frank
SoxB transcription factors and histone deacetylases (HDACs) are each major players in the regulation of neurogenesis, but a functional link between them has not been previously demonstrated. Here, we show that SoxB2 and Hdac2 act together to regulate neurogenesis in the cnidarian Hydractinia echinata during tissue homeostasis and head regeneration. We find that misexpression of SoxB genes modifies the number of neural cells in all life stages and interferes with head regeneration. Hdac2 was co-expressed with SoxB2, and its downregulation phenocopied SoxB2 knockdown. We also show that SoxB2 and Hdac2 promote each other's transcript levels, but Hdac2 counteracts this amplification cycle by deacetylating and destabilizing SoxB2 protein. Finally, we present evidence for conservation of these interactions in human neural progenitors. We hypothesize that crosstalk between SoxB transcription factors and Hdac2 is an ancient feature of metazoan neurogenesis and functions to stabilize the correct levels of these multifunctional proteins.

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Teaser

Using the early branching invertebrate model organism Hydractinia, Flici et al. show that SoxB2 and Hdac2, factors involved in the regulation of vertebrate neurogenesis, enhance each other's mRNA accumulation, but Hdac2 counteracts this cycle by destabilizing SoxB2 protein. This crosstalk helps to maintain optimal levels of these proteins to sustain neurogenesis.


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