Proneural enhancement by Notch overcomes Suppressor-of-Hairless repressor function in the developing Drosophila eye

Area of Science:

• Developmental biology
• Neuroscience
• Cell signaling

Background:

• Notch signaling is crucial for restricting neural fate via lateral inhibition.
• This process involves Notch intracellular domain coactivating Su(H)-mediated transcription of the Enhancer-of-split Complex.
• In Drosophila eye development, Notch also promotes neural fate independently of Su(H) and E(spl)-C, suggesting alternative signaling.

Purpose of the Study:

• To investigate the proneural enhancement pathway of Notch signaling.
• To understand the distinct roles of Su(H) in lateral inhibition and proneural enhancement.
• To elucidate the temporal regulation of neurogenesis by Notch.

Main Methods:

• Utilized genetic mosaics in Drosophila eye development.
• Analyzed the requirement of specific proteins like Kuzbanian, Presenilin, and Notch domains.
• Examined the effects of Su(H) absence and ectopic Notch signaling on neural differentiation.

Main Results:

• Proneural enhancement requires Kuzbanian, Notch extracellular domain, Presenilin, and Notch intracellular domain.
• Proneural enhancement becomes constitutive without Su(H), leading to premature differentiation and upregulation of Atonal and Senseless.
• Ectopic Notch signaling also induces premature differentiation.

Conclusions:

• Proneural enhancement and lateral inhibition share ligand binding and receptor processing but differ in Su(H)'s nuclear function.
• Su(H) directly represses neural development before Notch signaling.
• Notch signaling temporarily overcomes Su(H) repression for proneural enhancement, with lateral inhibition later restoring repression via E(spl)-C.