Hes5

Hes5, known as hairy and enhancer of split-5, is a member of the Hes family of basic helix-loop-helix transcriptional repressors in mammals. It functions as a downstream effector of Notch signaling and helps regulate cell fate decisions during development by suppressing differentiation programs in neural progenitor cells.

Hes5 proteins bind to DNA at Hes target sites and recruit corepressors to silence proneural genes, thereby maintaining the progenitor state and delaying neuronal differentiation. In the developing central nervous system and retina, Hes5 is broadly expressed in neural progenitor populations, and Notch activity promotes its transcription.

Expression of Hes5 is part of a broader Notch-Hes regulatory axis that interacts with other Hes family members to balance proliferation and differentiation. In some contexts, Hes family genes show dynamic, oscillatory expression patterns that can coordinate the timing of differentiation, though the extent of oscillation for Hes5 varies by tissue.

In humans, the gene encoding Hes5 is HES5. It is studied as a marker of neural progenitors and as a component of Notch-regulated neurogenesis; dysregulation of Hes5 pathways has potential relevance to neurodevelopmental processes and retinal development. Hes5 has homologs across vertebrates, with conserved roles in maintaining progenitor pools during CNS development.