Bhlhb5 and Prdm8 Form a Repressor Complex Involved in Neuronal Circuit Assembly

SarahE Ross, AlejandraE McCord, Cynthia Jung, Denize Atan, StephanieI Mok, Martin Hemberg, Tae Kyung Kim, John Salogiannis, Linda Hu, Sonia Cohen, Yingxi Lin, Dana Harrar, RoderickR McInnes, MichaelE Greenberg

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Abstract

Although transcription factors that repress gene expression play critical roles in nervous system development, their mechanism of action remains to be understood. Here, we report that the Olig-related transcription factor Bhlhb5 (also known as Bhlhe22) forms a repressor complex with the PR/SET domain protein, Prdm8. We find that Bhlhb5 binds to sequence-specific DNA elements and then recruits Prdm8, which mediates the repression of target genes. This interaction is critical for repressor function since mice lacking either Bhlhb5 or Prdm8 have strikingly similar cellular and behavioral phenotypes, including axonal mistargeting by neurons of the dorsal telencephalon and abnormal itch-like behavior. We provide evidence that Cadherin-11 functions as target of the Prdm8/Bhlhb5 repressor complex that must be repressed for proper neural circuit formation to occur. These findings suggest that Prdm8 is an obligate partner of Bhlhb5, forming a repressor complex that directs neural circuit assembly in part through the precise regulation of Cadherin-11. Ross and colleagues report that the Olig-related transcription factor Bhlhb5 forms a repressor complex with the PR/SET domain protein Prdm8. This complex ensures precise regulation of target genes such as Cadherin-11 and is essential for proper neuronal development.

Original languageEnglish (US)
Pages (from-to)292-303
Number of pages12
JournalNeuron
Volume73
Issue number2
DOIs
Publication statusPublished - Jan 26 2012

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ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Ross, S., McCord, A., Jung, C., Atan, D., Mok, S., Hemberg, M., ... Greenberg, M. (2012). Bhlhb5 and Prdm8 Form a Repressor Complex Involved in Neuronal Circuit Assembly. Neuron, 73(2), 292-303. https://doi.org/10.1016/j.neuron.2011.09.035