title: Loss of Gspt1l disturbs the patterning of the brain central arteries in zebrafish.
abstract: The cranial vasculature is crucial for the survival and development of the central nervous system and is closely related to brain pathologies. Characterizations of the underlying mechanisms by which cranial vessels acquire their stereotypic patterning remain to be the key interest in the cerebrovascular research. In this report, we show an interesting zebrafish cq37 mutant displaying aberrant patterning of the central arteries. Genetic mapping results indicate that the gene responsible for cq37 encodes G1 to S phase transition 1, like (Gspt1l) with a nonsense mutation. Complementation studies with a CRISPR-generated allele, as well as mRNA rescues, together strongly demonstrate that gspt1l is the cq37 gene. Zebrafish gspt1l is broadly expressed in the brain with enhanced expression in hindbrain during central artery sprouting. Further studies reveal that vascular endothelial growth factor (VEGF) signaling and unfolded protein response (UPR) pathway are activated in gspt1lcq37mutants. In addition, expression analysis shows that vegfa and activating transcription factor-4 (atf4) are strongly upregulated in regions of gspt1l expression. Our results suggest that loss of Gspt1l activates the UPR pathway, which in turn induces ectopic expression of vegfa via Atf4, thus disturbing the patterning of the central arteries.
authors.affiliation: Key Laboratory of Freshwater Fish Reproduction and Development, Ministry of Education, Laboratory of Molecular Developmental Biology, School of Life Sciences, Southwest University, Beibei, 400715 Chongqing, China.
authors.forename: Hongcheng
authors.initials: H
authors.lastname: Wang
authors.affiliation: Key Laboratory of Freshwater Fish Reproduction and Development, Ministry of Education, Laboratory of Molecular Developmental Biology, School of Life Sciences, Southwest University, Beibei, 400715 Chongqing, China. Electronic address: lluo@swu.edu.cn.
authors.forename: Lingfei
authors.initials: L
authors.lastname: Luo
authors.affiliation: Department of Endodontics and Operative Dentistry, Chongqing Key Laboratory for Oral Diseases and Biomedical Sciences, The Affiliated Hospital of Stomatology, Chongqing Medical University, 401147 Chongqing, China. Electronic address: proyangdeqin@foxmail.com.
authors.forename: Deqin
authors.initials: D
authors.lastname: Yang
mesh_terms: D051701:Activating Transcription Factor 4 / Q000235:genetics / Q000378:metabolism; D000818:Animals; D017209:Apoptosis / Q000235:genetics; D001158:Arteries / Q000196:embryology / Q000378:metabolism*; D001483:Base Sequence; D019521:Body Patterning / Q000235:genetics*; D001921:Brain / Q000098:blood supply*; D018797:Cell Cycle Proteins / Q000235:genetics* / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D017403:In Situ Hybridization; D017404:In Situ Hybridization, Fluorescence; D009154:Mutation; D018919:Neovascularization, Physiologic / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012249:Rhombencephalon / Q000098:blood supply; D056811:Unfolded Protein Response / Q000235:genetics; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism; D015027:Zebrafish / Q000196:embryology / Q000235:genetics* / Q000378:metabolism; D029961:Zebrafish Proteins / Q000235:genetics* / Q000378:metabolism
chemical_list: D018797:Cell Cycle Proteins; C000620511:Gspt1l protein, zebrafish; D042461:Vascular Endothelial Growth Factor A; D029961:Zebrafish Proteins; D051701:Activating Transcription Factor 4
keywords: Central artery; Gspt1l; Unfolded protein response; Vegfa; Zebrafish