{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nThe collection of abstracts provided centers on the role of TMEM67 in various ciliopathies, detailing its involvement in ciliary structure, signaling pathways (including both canonical and non‐canonical Wnt, Shh, and tyrosine kinase cascades), and developmental processes affecting multiple organs. None of these abstracts, however, include any direct reference to or data concerning the function of MIR4540. Consequently, there is no available evidence within these studies to infer or summarize a role for MIR4540."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "7"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn these studies, TMEM67 is highlighted as a key component of the ciliary transition zone, with its dysfunction linked to marked alterations in signaling activities (such as deregulated Wnt/β-catenin signaling and aberrant Shh pathway responses) that underlie the phenotypic variability seen in ciliopathy models. The research spans diverse experimental systems—from murine knockout models that recapitulate human syndromes like Meckel-Gruber and Joubert, to in vitro systems and zebrafish morphants—each demonstrating how TMEM67 dysfunction contributes to developmental malformations. Yet, even though microRNAs can be crucial regulators of gene expression in such pathways, none of the abstracts address a potential regulatory role for MIR4540."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nOverall, while the manuscripts provide valuable insights into the molecular mechanisms governing ciliary signaling and organ development via TMEM67, they do not shed light on a functional role for MIR4540. Further dedicated research would be required to determine if MIR4540 interacts with or influences these pathways, or if it has independent roles in the context of ciliopathies."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "4", "end_ref": "7"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Gayle B Collin, Jungyeon Won, Wanda L Hicks, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Meckelin is necessary for photoreceptor intraciliary transport and outer segment morphogenesis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Invest Ophthalmol Vis Sci (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1167/iovs.11-8766"}], "href": "https://doi.org/10.1167/iovs.11-8766"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22247471"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22247471"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Zakia A Abdelhamed, Gabrielle Wheway, Katarzyna Szymanska, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Variable expressivity of ciliopathy neurological phenotypes that encompass Meckel-Gruber syndrome and Joubert syndrome is caused by complex de-regulated ciliogenesis, Shh and Wnt signalling defects."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Mol Genet (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/hmg/dds546"}], "href": "https://doi.org/10.1093/hmg/dds546"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23283079"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23283079"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Amanda C Leightner, Cynthia J Hommerding, Ying Peng, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The Meckel syndrome protein meckelin (TMEM67) is a key regulator of cilia function but is not required for tissue planar polarity."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Mol Genet (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/hmg/ddt054"}], "href": "https://doi.org/10.1093/hmg/ddt054"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23393159"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23393159"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "E Du, Hong Li, Shunying Jin, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Evidence that TMEM67 causes polycystic kidney disease through activation of JNK/ERK-dependent pathways."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Biol Int (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/cbin.10081"}], "href": "https://doi.org/10.1002/cbin.10081"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23456819"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23456819"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Sveva Romani, Barbara Illi, Roberta De Mori, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The ciliary proteins Meckelin and Jouberin are required for retinoic acid-dependent neural differentiation of mouse embryonic stem cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Differentiation (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.diff.2014.02.005"}], "href": "https://doi.org/10.1016/j.diff.2014.02.005"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24613594"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24613594"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Zakia A Abdelhamed, Subaashini Natarajan, Gabrielle Wheway, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The Meckel-Gruber syndrome protein TMEM67 controls basal body positioning and epithelial branching morphogenesis in mice via the non-canonical Wnt pathway."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Dis Model Mech (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1242/dmm.019083"}], "href": "https://doi.org/10.1242/dmm.019083"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26035863"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26035863"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Zakia A Abdelhamed, Dina I Abdelmottaleb, Mohammed E El-Asrag, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The ciliary Frizzled-like receptor Tmem67 regulates canonical Wnt/β-catenin signalling in the developing cerebellum via Hoxb5."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Sci Rep (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41598-019-41940-5"}], "href": "https://doi.org/10.1038/s41598-019-41940-5"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30931988"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30931988"}]}]}]}