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Srp54 Promotes Motor Neuron Development and is Required for Motility in Zebrafish: Implications for SMA
Srp54 Promotes Motor Neuron Development and is Required for Motility in Zebrafish: Implications for SMA
상세정보
- 자료유형
- 학위논문 서양
- 최종처리일시
- 20260202105635
- ISBN
- 9798297962828
- DDC
- 616
- 서명/저자
- Srp54 Promotes Motor Neuron Development and is Required for Motility in Zebrafish: Implications for SMA
- 발행사항
- [Sl] : The Ohio State University, 2025
- 발행사항
- Ann Arbor : ProQuest Dissertations & Theses, 2025
- 형태사항
- 204 p
- 주기사항
- Source: Dissertations Abstracts International, Volume: 87-05, Section: B.
- 주기사항
- Advisor: Kolb, Stephen J.
- 학위논문주기
- Thesis (Ph.D.)--The Ohio State University, 2025.
- 초록/해제
- 요약Spinal muscular atrophy (SMA) is a recessively inherited motor neuron disease that develops from deficient levels of the ubiquitously expressed Survival of Motor Neuron (SMN) protein. The molecular mechanism linking deficient SMN protein to motor neuron selective death in SMA is unknown. SMN protein is implicated in multiple cellular functions including signal recognition particle (SRP) assembly. The SRP is a highly conserved ribonucleoprotein (RNP) that translocates a subset of secreted and integral membrane proteins to the endoplasmic reticulum for proper localization and membrane insertion, respectively. The most conserved SRP protein component, SRP54, is implicated in the molecular etiology of spinal muscular atrophy SMA. SMN protein is necessary to assemble the SRP54 onto the SRP in Xenopus laevis oocytes; thus, SMN deficiency may attenuate SRP function and contribute to motor neuron death in SMA patients. To test whether an association between SMN and SRP54 occurs in another vertebrate, we probed for Srp54 association with Smn in 2 days postfertilization (dpf) zebrafish protein lysate. Results do not support a Smn protein association with Srp54 protein in HEK293T cells, and results are inconclusive in zebrafish embryo lysate at 2 days postfertilization. However, Smn protein may affect SRP function outside of assembly and contribute to motor neuron degeneration. We proceeded to test the requirement of Srp54 protein in motor neuron development using zebrafish embryos homozygous for a srp54 nonsense mutation (srp54-/-). The first gross phenotype that distinguishes srp54-/- embryos from srp54+/+ and srp54+/- siblings is reduced motility at 30 hours postfertilization (hpf). To investigate the underlying cause of immotility, we imaged caudal primary motor axons at 30 hpf and detected reduced axon length and branching in srp54-/- embryos compared to srp54+/+ and srp54+/- siblings. Shorter and less branched axons at 30 hpf indicate that reduced motor neuron innervation may contribute to immotility. We also examined additional neural, secretory, and migratory cell types at 30 hpf to assess whether motor neurons are especially vulnerable to Srp54 deficiency. Of the cell types evaluated, only a marker of the hatching gland had distinct expression pattern alterations in srp54-/- embryos at this developmental stage. Our findings suggest that Srp54 deficiency results in motor neuron developmental defects and support the hypothesis that SRP54 may influence motor neuron selectivity in SMA.
- 일반주제명
- Neurosciences
- 일반주제명
- Biochemistry
- 일반주제명
- Genetics
- 일반주제명
- Biology
- 일반주제명
- Neurobiology
- 일반주제명
- Molecular biology
- 일반주제명
- Developmental biology
- 키워드
- Zebrafish
- 키워드
- Motor neuron
- 키워드
- Neuron disease
- 기타저자
- The Ohio State University Neuroscience Graduate Studies Program
- 기본자료저록
- Dissertations Abstracts International. 87-05B.
- 전자적 위치 및 접속
- 로그인 후 원문을 볼 수 있습니다.
MARC
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■1001 ▼aLosievski, Nikaela.
■24510▼aSrp54 Promotes Motor Neuron Development and is Required for Motility in Zebrafish: Implications for SMA
■260 ▼a[Sl]▼bThe Ohio State University▼c2025
■260 1▼aAnn Arbor▼bProQuest Dissertations & Theses▼c2025
■300 ▼a204 p
■500 ▼aSource: Dissertations Abstracts International, Volume: 87-05, Section: B.
■500 ▼aAdvisor: Kolb, Stephen J.
■5021 ▼aThesis (Ph.D.)--The Ohio State University, 2025.
■520 ▼aSpinal muscular atrophy (SMA) is a recessively inherited motor neuron disease that develops from deficient levels of the ubiquitously expressed Survival of Motor Neuron (SMN) protein. The molecular mechanism linking deficient SMN protein to motor neuron selective death in SMA is unknown. SMN protein is implicated in multiple cellular functions including signal recognition particle (SRP) assembly. The SRP is a highly conserved ribonucleoprotein (RNP) that translocates a subset of secreted and integral membrane proteins to the endoplasmic reticulum for proper localization and membrane insertion, respectively. The most conserved SRP protein component, SRP54, is implicated in the molecular etiology of spinal muscular atrophy SMA. SMN protein is necessary to assemble the SRP54 onto the SRP in Xenopus laevis oocytes; thus, SMN deficiency may attenuate SRP function and contribute to motor neuron death in SMA patients. To test whether an association between SMN and SRP54 occurs in another vertebrate, we probed for Srp54 association with Smn in 2 days postfertilization (dpf) zebrafish protein lysate. Results do not support a Smn protein association with Srp54 protein in HEK293T cells, and results are inconclusive in zebrafish embryo lysate at 2 days postfertilization. However, Smn protein may affect SRP function outside of assembly and contribute to motor neuron degeneration. We proceeded to test the requirement of Srp54 protein in motor neuron development using zebrafish embryos homozygous for a srp54 nonsense mutation (srp54-/-). The first gross phenotype that distinguishes srp54-/- embryos from srp54+/+ and srp54+/- siblings is reduced motility at 30 hours postfertilization (hpf). To investigate the underlying cause of immotility, we imaged caudal primary motor axons at 30 hpf and detected reduced axon length and branching in srp54-/- embryos compared to srp54+/+ and srp54+/- siblings. Shorter and less branched axons at 30 hpf indicate that reduced motor neuron innervation may contribute to immotility. We also examined additional neural, secretory, and migratory cell types at 30 hpf to assess whether motor neurons are especially vulnerable to Srp54 deficiency. Of the cell types evaluated, only a marker of the hatching gland had distinct expression pattern alterations in srp54-/- embryos at this developmental stage. Our findings suggest that Srp54 deficiency results in motor neuron developmental defects and support the hypothesis that SRP54 may influence motor neuron selectivity in SMA.
■590 ▼aSchool code: 0168.
■650 4▼aNeurosciences
■650 4▼aBiochemistry
■650 4▼aGenetics
■650 4▼aBiology
■650 4▼aNeurobiology
■650 4▼aMolecular biology
■650 4▼aDevelopmental biology
■653 ▼aSignal recognition particle
■653 ▼aSpinal muscular atrophy
■653 ▼aZebrafish
■653 ▼aMotor neuron
■653 ▼aNeuron disease
■690 ▼a0317
■690 ▼a0487
■690 ▼a0758
■690 ▼a0369
■690 ▼a0306
■690 ▼a0307
■71020▼aThe Ohio State University▼bNeuroscience Graduate Studies Program.
■7730 ▼tDissertations Abstracts International▼g87-05B.
■790 ▼a0168
■791 ▼aPh.D.
■792 ▼a2025
■793 ▼aEnglish
■85640▼uhttp://www.riss.kr/pdu/ddodLink.do?id=T17360903▼nKERIS▼z이 자료의 원문은 한국교육학술정보원에서 제공합니다.
