Activated Notch Disrupts the Initial Patterning of Dopaminergic Spinal Cord Neurons

Abstract

Dopaminergic spinal cord neurons differentiate in the ventral spinal cord in a nonrandom dispersed pattern. To test whether Notch signaling was involved in generating the pattern of this neuron population as with others, we overexpressed a constitutively active form of Xenopus Notch (XotchΔE) in developing frog embryos. Overexpression was targeted to half the spinal cord by injecting activated Notch RNA into one blastomere at the two-cell stage. Injected animals showed morphological differences on the injected side including reduced numbers of dopaminergic spinal cord neurons. This is consistent with a role for Notch signaling in establishing the fate of this population in the developing spinal cord. At a later stage of development, dopaminergic neurons continued to differentiate on both sides of the spinal cord, but the difference between experimental and control columns remained constant. This is consistent with transient activation of Notch disrupting the fate of the earliest (primary) but not later (secondary) dopaminergic neurons. The precursors to secondary neurons appear to be refractory to Notch signaling at earlier stages of development.

Asymmetric Cell Division and Notch Signaling Specify Dopaminergic Neurons in Drosophila

“…Interestingly, a repressive role for Notch on DA neuronal specification is also observed in the frog spinal cord [60]. It was also reported recently that loss of Notch signaling in the zebrafish led to expansion of cell numbers of DA neurons during development [61].…”