# Oscillatory DeltaC Expression in Neural Progenitors Primes the Prototype of Forebrain Development

## TL;DR

This study shows that DeltaC (dlc) oscillations in zebrafish neural progenitors are crucial for early forebrain development, revealing a foundational role for Notch signaling in vertebrates.

## Contribution

The first detection of oscillatory dlc expression in the zebrafish forebrain and its role in neurogenesis.

## Key findings

- Oscillatory dlc expression was detected in the zebrafish developing forebrain.
- Inhibition of the dlc-involved Notch pathway impaired neuronal differentiation in zebrafish.
- Zebrafish dlc signaling represents a foundational prototype for vertebrate forebrain development.

## Abstract

Notch signaling plays a pivotal role in regulating various developmental processes, particularly in controlling the timing of neuronal production within the developing neocortex. Central to this regulatory mechanism is the oscillatory pattern of Delta, which functions as a developmental clock modulator. Its deficiency profoundly impairs mammalian brain formation, highlighting its fundamental role in brain development. However, zebrafish carrying a mutation in the functional ortholog DeltaC (dlc) within their functional ortholog exhibit an intact forebrain structure, implying evolutionary variations in Notch signaling within the forebrain. In this study, we unveil the distinct yet analogous expression profiles of Delta and Her genes in the developing vertebrate forebrain. Specifically, for the first time, we detected the oscillatory expression of the Delta gene dlc in the developing zebrafish forebrain. Although this oscillatory pattern appeared irregular and was not pervasive among the progenitor population, attenuation of the dlc-involved Notch pathway using a γ-secretase inhibitor impaired neuronal differentiation in the developing zebrafish forebrain, revealing the indispensable role of the dlc-involved Notch pathway in regulating early zebrafish neurogenesis. Taken together, our results demonstrate the foundational prototype of dlc-involved Notch signaling in the developing zebrafish forebrains, upon which the intricate patterns of the mammalian neocortex may have been sculpted.

The online version contains supplementary material available at 10.1007/s12035-024-04530-9.