Two intrinsic timing mechanisms set start and end times for dendritic arborization of a nociceptive neuron.

Choreographic dendritic arborization takes place within a defined time frame, but the timing mechanism is currently not known. Here, we report that the precisely timed regulatory circuit triggers an initial dendritic growth activity, whereas the precisely timed regulatory circuit signals a subsequent developmental decline in dendritic growth ability, hence restricting dendritic arborization within a set time frame. Loss-of-function mutations in the microRNA gene cause limited dendritic outgrowth, whereas loss-of-function mutations in its direct target, the transcription factor gene, cause precocious and excessive outgrowth. In contrast, loss-of-function mutations in the microRNA gene prevent a developmental decline in dendritic growth ability, whereas loss-of-function mutations in its direct target, the tripartite motif protein gene, cause further decline. and regulatory circuits are expressed in the right place at the right time to set start and end times for dendritic arborization. Replacing the upstream cis-regulatory sequence at the locus with a late-onset upstream cis-regulatory sequence delays dendrite arborization, whereas replacing the upstream cis-regulatory sequence at the locus with an early-onset upstream cis-regulatory sequence causes a precocious decline in dendritic growth ability. Our results indicate that the and the regulatory circuits control the timing of dendrite arborization through antagonistic regulation of the DMA-1 receptor level on dendrites. The LIN-14 transcription factor likely directly represses gene expression through a transcriptional means, whereas the LIN-41 tripartite motif protein likely indirectly promotes gene expression through a posttranscriptional means.