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Neural Development: bHLH Genes

  1. Anna Philpott

Published Online: 15 FEB 2010

DOI: 10.1002/9780470015902.a0000827.pub2



How to Cite

Philpott, A. 2010. Neural Development: bHLH Genes. eLS. .

Author Information

  1. University of Cambridge, Department of Oncology, Hutchison/MRC Research Centre, Addenbrookes Hospital, Cambridge, UK

Publication History

  1. Published Online: 15 FEB 2010


Transcription factors of the basic helix–loop–helix (bHLH) class are involved in the determination of precursor cells towards neural (proneural) and other cell fates. The proneural members of this class constitute a particular subset of bHLH proteins that are arranged in a cascade that affects different stages of neuronal commitment and differentiation, and act in a combinatorial code along with other transcription factors to specify neuronal identity. Proneural proteins themselves are a target of regulation by ID and HES proteins among others, and are involved in setting up a negative feedback pathway of lateral inhibition involving NOTCH and DELTA signalling. In addition, the activities of bHLHs are also subject to control by posttranslational modification and degradation. Finally, recent analyses have begun to identify the direct downstream targets of bHLH genes in the nervous system, and this is shedding light on the mechanisms ensuring specificity of the individual bHLH proteins.

Key concepts:

  • bHLH proneural transcription factors have multiple direct downstream transcriptional targets including other transcription factors, signal transducers and cytoskeletal modifiers.

  • bHLH proneural transcription factors act in a combinatorial code to confer neuronal subtype identity.

  • bHLH transcription factors are regulated posttranslationally by mechanisms including phosphorylation and ubiquitin-mediated proteolysis.

  • bHLH proneural transcription factors have multiple downstream targets that orchestrate neural differentiation.

  • Negative regulators of bHLH proneural proteins such as HES and ID proteins act by dimerizing with and sequestering E protein partners.

  • Lateral inhibition mediated by the NOTCHDELTA pathway limits the number of neurons that differentiate from the pool of neuronal precursors.


  • proneural;
  • neurogenesis;
  • transcription factor;
  • lateral inhibition;
  • differentiation;
  • determination