{"doi":"10.1101/2021.08.31.458402","title":"Two intrinsic timing mechanisms set start and end times for dendritic arborization of a nociceptive neuron","abstract":"Summary 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 lin-4-lin-14 regulatory circuit triggers an initial dendritic growth activity whereas the precisely timed lin-28-let-7-lin-41 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 lin-4 microRNA gene cause limited dendritic outgrowth whereas loss-of-function mutations in its direct target, the lin-14 transcription factor gene, cause precocious and excessive outgrowth. In contrast, loss-of-function mutations in the let-7 microRNA gene prevent a developmental decline in dendritic growth ability whereas loss-of-function mutations in its upstream regulator, the lin-28 RNA-binding protein gene, and its direct target, the lin-41 tripartite motif protein gene, cause further decline. lin-4 and let-7 regulatory circuits are expressed in the right place at the right time to set start and end times for PVD dendritic arborization. Replacing the endogenous lin-4 promoter at the lin-4 locus with a late-onset let-7 promoter delays PVD dendrite arborization whereas replacing the endogenous let-7 promoter at the let-7 locus with an early-onset lin-4 promoter causes precocious decline in dendritic growth ability in PVD neurons. Our results indicate that the lin-4-lin-14 and the lin-28-let-7-lin-41 regulatory circuits control the timing of dendrite arborization through antagonistic regulation of the DMA-1 receptor level on dendrites. The LIN-14 transcription factor directly represses the dma-1 gene expression through a transcriptional means whereas the LIN-41 tripartite motif protein indirectly activates the dma-1 gene expression through a post-transcriptional means.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2021,"id":226362,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9516,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":373581,"name":"Yan Zou","orcid":"0000-0002-4743-4995","position":1,"is_corresponding":false},{"id":488803,"name":"HaoSheng Sun","orcid":"0000-0003-3919-559X","position":2,"is_corresponding":false},{"id":829364,"name":"Kelsie Eichel","orcid":"0000-0003-4507-5949","position":3,"is_corresponding":false},{"id":829775,"name":"Meiyu Shao","orcid":null,"position":4,"is_corresponding":false},{"id":314620,"name":"Kang Shen","orcid":"0000-0003-4059-8249","position":5,"is_corresponding":false},{"id":821431,"name":"Chieh Chang","orcid":"0000-0003-3476-2751","position":6,"is_corresponding":false},{"id":821986,"name":"Nobuko Suzuki","orcid":null,"position":0,"is_corresponding":true}],"reference_count":70,"raw_metadata":null,"created_at":"2026-07-18T23:54:34.185847Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}