{"id":{"repo_id":"nus","oai_identifier":"oai:scholarbank.nus.edu.sg:10635/163046"},"canonical_url":"https://search.dev.ndltd.org/etd/nus/oai:scholarbank.nus.edu.sg:10635/163046","repository":{"repo_id":"nus","name":"National University of Singapore","base_url":"https://scholarbank.nus.edu.sg/oai/request"},"display":{"title":"MOTONEURON MAINTENANCE DEFECTS AND NON-CELL AUTONOMOUS CONTRIBUTIONS BY SCHWANN CELLS IN ZEBRAFISH MUTANT AND MORPHANT MODELS FOR SPINAL MUSCULAR ATROPHY","abstract":"Survival Motoneuron (SMN) protein deficiency results in motoneuron (MN) loss in Spinal Muscular Atrophy (SMA) patients. SMN is encoded by SMN1 and SMN2 which differ in a C6T nucleotide leading to differential splicing of exon 7. My novel zebrafish smn2 mutant established that C6T transition in hSMN2 disrupts an exonic splicing enhancer to cause aberrant splicing. The smn2 mutant exhibits features reminiscent of milder SMA patients, i.e. motoneuron loss, locomotor deficiencies, muscle wasting and early lethality. Studies in SMA animal models suggested a non-cell autonomous contribution of Schwann cell defects to MN degeneration. Supporting this, I found that restoration of Smn in Schwann cell precursors (SCPs) of smn morphants partially ameliorates MN defects. Transcriptome analysis of Smn deficient SCPs to unravel potential non-cell autonomous regulators identified crispld1b and mid1ip1b. crispld1b knock-out disrupted SCP migration and partially reproduced MN branching defect, suggesting it as a novel target of Smn in SCPs.","abstract_html":"Survival Motoneuron (SMN) protein deficiency results in motoneuron (MN) loss in Spinal Muscular Atrophy (SMA) patients. SMN is encoded by SMN1 and SMN2 which differ in a C6T nucleotide leading to differential splicing of exon 7. My novel zebrafish smn2 mutant established that C6T transition in hSMN2 disrupts an exonic splicing enhancer to cause aberrant splicing. The smn2 mutant exhibits features reminiscent of milder SMA patients, i.e. motoneuron loss, locomotor deficiencies, muscle wasting and early lethality. Studies in SMA animal models suggested a non-cell autonomous contribution of Schwann cell defects to MN degeneration. Supporting this, I found that restoration of Smn in Schwann cell precursors (SCPs) of smn morphants partially ameliorates MN defects. Transcriptome analysis of Smn deficient SCPs to unravel potential non-cell autonomous regulators identified crispld1b and mid1ip1b. crispld1b knock-out disrupted SCP migration and partially reproduced MN branching defect, suggesting it as a novel target of Smn in SCPs.","abstract_has_math":false,"creators":["TAY HUIPING SHERMAINE"],"institution":null,"degree_name":null,"degree_level":null,"degree_discipline":null,"degree_department":null,"school":null,"contributors":[],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2019,"date_issued":"2019-08-22","date_published":"2019-08-22","updated_at":"2026-07-24T03:33:22Z","subjects":["sma, smn, zebrafish mutant model, motoneuron, non-cell autonomous, Schwann cell"],"languages":[],"rights":[],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":null,"outbound_label":null,"outbound_source":null},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:creator","label":"Author","values":["TAY HUIPING SHERMAINE"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date.issued","label":"Date","values":["2019-08-22"]},{"key":"dc:relation.isreferencedby","label":"Dc Relation Isreferencedby","values":["https://scholarbank.nus.edu.sg/handle/10635/163046"]},{"key":"dc:type","label":"Dc Type","values":["Thesis"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["sma, smn, zebrafish mutant model, motoneuron, non-cell autonomous, Schwann cell"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier.uri","label":"Identifier URI","values":["https://scholarbank.nus.edu.sg/bitstreams/31ffbc6a-437f-4fb7-9d54-0b246b6c54f1/download","https://scholarbank.nus.edu.sg/bitstreams/e4a5fa58-943d-4afc-bcd3-d0675714f0b0/download","https://scholarbank.nus.edu.sg/bitstreams/9336f5c6-5ce2-4ce1-8a40-7343c31c1c0a/download","https://scholarbank.nus.edu.sg/bitstreams/2e5d16e6-cc5d-42e0-bbc0-95df3f7c9aa6/download","https://scholarbank.nus.edu.sg/bitstreams/6a1a1308-7c72-42d7-96f8-c4e35601452c/download","https://scholarbank.nus.edu.sg/bitstreams/7b69c3e1-5151-410d-b941-38da7c677c28/download","https://scholarbank.nus.edu.sg/bitstreams/ed0798dd-3950-44d6-be1b-67550ab8a52e/download","https://scholarbank.nus.edu.sg/bitstreams/9f64af22-1b29-4aef-b347-fa84df5c3798/download"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["Survival Motoneuron (SMN) protein deficiency results in motoneuron (MN) loss in Spinal Muscular Atrophy (SMA) patients. 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Transcriptome analysis of Smn deficient SCPs to unravel potential non-cell autonomous regulators identified crispld1b and mid1ip1b. crispld1b knock-out disrupted SCP migration and partially reproduced MN branching defect, suggesting it as a novel target of Smn in SCPs."]},{"key":"dc:format.checksum.md5","label":"Dc Format Checksum Md5","values":["49504a38fee26d40192da4fab1d110c9","c89207d8c41a71cf27c1315c959d553c","943faa4c7e8464a15d2c6dec9106c7a6","850088e27b535b4ff8b8d263317a6141","f5b32401d341f3d3510a683db9823288","762a72e6a91bfb5a908292fe544f9998","2713fdbfce4a8d1805b7e6b22a201a78","bb8688f04c8b20ed511ef9c28aa122cc","a8670569ce6742f878964e18204fc193"]},{"key":"dc:title","label":"Title","values":["MOTONEURON MAINTENANCE DEFECTS AND NON-CELL AUTONOMOUS CONTRIBUTIONS BY SCHWANN CELLS IN ZEBRAFISH MUTANT AND MORPHANT MODELS FOR SPINAL MUSCULAR ATROPHY"]}]}],"canonical_facts":{"dc:creator":["TAY HUIPING SHERMAINE"],"dc:date.issued":["2019-08-22"],"dc:description.abstract":["Survival Motoneuron (SMN) protein deficiency results in motoneuron (MN) loss in Spinal Muscular Atrophy (SMA) patients. 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