Prpf4(pre-mRNA processing factor 4),a key component of spliceosome,plays critical roles in pre-mRNA splicing and its mutations result in retinitis pigmentosa due to photoreceptor defects.In this study,we characterized...Prpf4(pre-mRNA processing factor 4),a key component of spliceosome,plays critical roles in pre-mRNA splicing and its mutations result in retinitis pigmentosa due to photoreceptor defects.In this study,we characterized a zebrafishharboring a Tol2 transposon-based gene trap cassette in the third intron of the prpf4 gene.Cells in the brain and spinal cord gradually undergo p53-dependent apoptosis after 28 hpf insuggesting that a widespread function of prpf4 in neural cell survival.In addition,prpf4 is essential for survival of posterior lateral line primordial(pLLP)cells.prpf4 deficiency perturbs Fgf,and chemokine signaling pathways and impairs pLLP migration.RNA-Seq analysis suggests that prpf4 deficiency may impair spliceosome assembly,leading to compensatory upregulation of core spliceosomal genes and alteration of pre-mRNA splicing.Taken together,our studies uncover an essential role of prpf4 in pre-m RNA splicing,cell survival and pLLP migration.展开更多
The zebrafish sensory posterior lateral line(pLL)has become an attractive model for studying collective cell migration and cell morphogenesis.Recent studies have indicated that chemokine,Wnt/β-catenin,Fgf,and Delta-N...The zebrafish sensory posterior lateral line(pLL)has become an attractive model for studying collective cell migration and cell morphogenesis.Recent studies have indicated that chemokine,Wnt/β-catenin,Fgf,and Delta-Notch signaling pathways participate in regulating pLL development.However,it remains unclear whether TGFβsignaling pathway is involved in pLL development.Here we report a critical role of TGFβ1 in regulating morphogenesis of the pLL primordium(pLLP).The tgfβ1a gene is abundantly expressed in the lateral line primordium.Knockdown or knockout of tgfβ1a leads to a reduction of neuromast number,an increase of inter-neuromast distance,and a reduced number of hair cells.The aberrant morphogenesis in embryos depleted of tgfβ1a correlates with the reduced expression of atoh1a,deltaA,and n-cadherin/cdh2,which are known important regulators of the pLLP morphogenesis.Like tgfβ1a depletion,knockdown of smad5 that expresses in the pLLP,affects pLLP development whereas overexpression of a constitutive active Smad5 isoform rescues the defects in embryos depleted of tgfβ1a,indicating that Smad5 mediates tgfβ1a function in pLLP development.Therefore,TGFβ/Smad5 signaling plays an important role in the zebrafish lateral line formation.展开更多
基金supported by the National Natural Science Foundation of China(31772042)Ramóny Cajal grant(RYC2020-030365-I)+1 种基金Xunta de Galicia for supporting the program(Excelencia-ED431F2022/01)the Key Research&Development Program of Zhejiang Province(2021C02015).
基金financially supported by grants from the National Natural Science Foundation of China (Nos.31522035,31371460 and 31590832)
文摘Prpf4(pre-mRNA processing factor 4),a key component of spliceosome,plays critical roles in pre-mRNA splicing and its mutations result in retinitis pigmentosa due to photoreceptor defects.In this study,we characterized a zebrafishharboring a Tol2 transposon-based gene trap cassette in the third intron of the prpf4 gene.Cells in the brain and spinal cord gradually undergo p53-dependent apoptosis after 28 hpf insuggesting that a widespread function of prpf4 in neural cell survival.In addition,prpf4 is essential for survival of posterior lateral line primordial(pLLP)cells.prpf4 deficiency perturbs Fgf,and chemokine signaling pathways and impairs pLLP migration.RNA-Seq analysis suggests that prpf4 deficiency may impair spliceosome assembly,leading to compensatory upregulation of core spliceosomal genes and alteration of pre-mRNA splicing.Taken together,our studies uncover an essential role of prpf4 in pre-m RNA splicing,cell survival and pLLP migration.
基金This work was financially supported by grants from the National Natural Science Foundation of China(#31371460)Major Science Programs of China(#2012CB945101 and#2011CB943800)。
文摘The zebrafish sensory posterior lateral line(pLL)has become an attractive model for studying collective cell migration and cell morphogenesis.Recent studies have indicated that chemokine,Wnt/β-catenin,Fgf,and Delta-Notch signaling pathways participate in regulating pLL development.However,it remains unclear whether TGFβsignaling pathway is involved in pLL development.Here we report a critical role of TGFβ1 in regulating morphogenesis of the pLL primordium(pLLP).The tgfβ1a gene is abundantly expressed in the lateral line primordium.Knockdown or knockout of tgfβ1a leads to a reduction of neuromast number,an increase of inter-neuromast distance,and a reduced number of hair cells.The aberrant morphogenesis in embryos depleted of tgfβ1a correlates with the reduced expression of atoh1a,deltaA,and n-cadherin/cdh2,which are known important regulators of the pLLP morphogenesis.Like tgfβ1a depletion,knockdown of smad5 that expresses in the pLLP,affects pLLP development whereas overexpression of a constitutive active Smad5 isoform rescues the defects in embryos depleted of tgfβ1a,indicating that Smad5 mediates tgfβ1a function in pLLP development.Therefore,TGFβ/Smad5 signaling plays an important role in the zebrafish lateral line formation.
