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ABSTRACT

Wiring an animal brain requires a staggering number of neurons (~1011 in humans) to precisely connect with a specific set of synaptic partners. Errors in this process are associated with disorders such as autism and schizophrenia. During the incredibly complex process of neuronal circuit formation neurons go through several, complex developmental steps. The steps involved are neuron-type specific and need to occur at precise times in development. This requires neurons to express the right set of genes at the right time, but how do developing neurons know which genes to express when?

Using a combination of single-cell RNA-Seq and classical genetics, we recently described a unique global temporal regulator in developing fly visual system neurons. We found that the steroid hormone Ecdysone induces synchronous expression of several dynamic transcription factors (TFs) during development across all neuron-types. While the hormone induces the same TFs across all visual system neurons, these factors control a cell-type specific set of target genes and depend upon neuron-type specific TFs for target gene specificity. This work demonstrates a general principle wherein timing is controlled by cell-extrinsic cues (such as hormones and stimulation of neuronal activity), which work with neuron-type specific transcription factors to ensure the proper timing of wiring-regulating genes. 

Host: Dr. Patrick McGrath