{"doi":"10.1016/j.cub.2020.01.027","title":"Epithelial Planar Bipolarity Emerges from Notch-Mediated Asymmetric Inhibition of Emx2","abstract":"Most plane-polarized tissues are formed by identically oriented cells [1, 2]. A notable exception occurs in the vertebrate vestibular system and lateral-line neuromasts, where mechanosensory hair cells orient along a single axis but in opposite directions to generate bipolar epithelia [3-5]. In zebrafish neuromasts, pairs of hair cells arise from the division of a non-sensory progenitor [6, 7] and acquire opposing planar polarity via the asymmetric expression of the polarity-determinant transcription factor Emx2 [8-11]. Here, we reveal the initial symmetry-breaking step by decrypting the developmental trajectory of hair cells using single-cell RNA sequencing (scRNA-seq), diffusion pseudotime analysis, lineage tracing, and mutagenesis. We show that Emx2 is absent in non-sensory epithelial cells, begins expression in hair-cell progenitors, and is downregulated in one of the sibling hair cells via signaling through the Notch1a receptor. Analysis of Emx2-deficient specimens, in which every hair cell adopts an identical direction, indicates that Emx2 asymmetry does not result from auto-regulatory feedback. These data reveal a two-tiered mechanism by which the symmetric monodirectional ground state of the epithelium is inverted by deterministic initiation of Emx2 expression in hair-cell progenitors and a subsequent stochastic repression of Emx2 in one of the sibling hair cells breaks directional symmetry to establish planar bipolarity.","journal":"Current Biology","year":2020,"id":11661,"datarank":0.5606504427425053,"base_score":3.7376696182833684,"endowment":3.7376696182833684,"self_citation_contribution":0.5606504427425053,"citation_network_contribution":0.0,"self_endowment_contribution":0.5606504427425053,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":41,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.0573,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-03-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":31685,"name":"Subarna Palit","orcid":null,"position":1,"is_corresponding":false},{"id":94114,"name":"Jerónimo R. Miranda-Rodríguez","orcid":"0000-0002-2775-6719","position":2,"is_corresponding":false},{"id":94115,"name":"Aleksandar Janjic","orcid":"0000-0001-7180-5381","position":3,"is_corresponding":false},{"id":6099,"name":"Anika Böttcher","orcid":"0000-0001-5473-3136","position":4,"is_corresponding":false},{"id":2920,"name":"Heiko Lickert","orcid":"0000-0002-4597-8825","position":5,"is_corresponding":false},{"id":36050,"name":"Wolfgang Enard","orcid":"0000-0002-4056-0550","position":6,"is_corresponding":false},{"id":42,"name":"Fabian Joachim Theis","orcid":"0000-0002-2419-1943","position":7,"is_corresponding":false},{"id":94116,"name":"Hernán López-Schier","orcid":null,"position":8,"is_corresponding":false},{"id":94117,"name":"Hernán López‐Schier","orcid":"0000-0001-7925-7439","position":9,"is_corresponding":false},{"id":94113,"name":"Eva L. Kozak","orcid":null,"position":0,"is_corresponding":true}],"reference_count":57,"raw_metadata":null,"created_at":"2026-03-01T18:20:47.508186Z","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":[]}