Abstract
Temporal patterning is a seminal method of expanding neuronal diversity. Here we unravel a mechanism decoding neural stem cell temporal gene expression and transforming it into discrete neuronal fates. This mechanism is characterized by hierarchical gene expression. First, Drosophila neuroblasts express opposing temporal gradients of RNA-binding proteins, Imp and Syp. These proteins promote or inhibit chinmo translation, yielding a descending neuronal gradient. Together, first and second-layer temporal factors define a temporal expression window of BTB-zinc finger nuclear protein, Mamo. The precise temporal induction of Mamo is achieved via both transcriptional and post-transcriptional regulation. Finally, Mamo is essential for the temporally defined, terminal identity of α'/β' mushroom body neurons and identity maintenance. We describe a straightforward paradigm of temporal fate specification where diverse neuronal fates are defined via integrating multiple layers of gene regulation. The neurodevelopmental roles of orthologous/related mammalian genes suggest a fundamental conservation of this mechanism in brain development.
Highlights
The brain is a complicated organ which requires specific connections between neurons to form circuits, and many neuronal types with variations in morphology, neurotransmitters and receptors
These results indicate a temporal induction of Mamo in the prospective a’/b’ neurons, consistent with Mamo being a target of weak Chinmo within the young neuron stage of neuronal maturation. g neurons, which express high Chinmo in early larval stages, begin to express Mamo during puparium formation (Figure 1—figure supplement 1C)
To test if Mamo lies downstream of weak Chinmo, we examined the effect of altering Chinmo levels on Mamo expression
Summary
The brain is a complicated organ which requires specific connections between neurons to form circuits, and many neuronal types with variations in morphology, neurotransmitters and receptors. In the mouse neocortex, radial glial progenitors (RGP) are multipotent—they produce a variety of neuron types organized sequentially into six layers, and produce glia (Adnani et al, 2018). Lineage tracing of a single antennal lobe (AL) stem cell revealed a remarkable series of 40 morphologically distinct neuronal types generated sequentially (Lin et al, 2012; Yu et al, 2010). In light of these observations, a fundamental goal is to understand how distinct neuronal types correctly differentiate from a single progenitor. While scientists have discovered key temporal factors expressed in neural progenitors, much less is understood about how these signals are interpreted, that is what factors lie downstream of the specification signals to determine distinct neuronal temporal fates
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