Source data supporting "Pathway specific effects of ADSL deficiency on neurodevelopment"

Posted on 26.01.2022 - 03:25 authored by Travis Stracker

Source raw microscopy data for Figure 2-8 of eLife article Dutto et al, 2022, Pathway specific effects of ADSL deficiency on neurodevelopment.

Abstract:

Adenylosuccinate Lyase (ADSL) functions in the de novo purine biosynthesis pathway. ADSL deficiency (ADSLD) causes numerous neurodevelopmental pathologies, including microcephaly and autism spectrum disorder. ADSLD patients have normal purine nucleotide levels but exhibit accumulation of the dephosphorylated ADSL substrates SAICAr and S-Ado. SAICAr was implicated in the neurotoxic effects of ADSLD, although its role remains unknown. We examined the effects of ADSL depletion in human cells and found increased DNA damage signaling, that was rescued by nucleosides, and impaired primary ciliogenesis, that was rescued by reducing SAICAr. By analyzing ADSL deficient chicken and zebrafish embryos we observed impaired neurogenesis and microcephaly, and neuroprogenitor attrition in zebrafish was rescued by reducing SAICAr. Zebrafish embryos also displayed phenotypes commonly linked to ciliopathies. Our results suggest that both reduced purine levels and SAICAr accumulation contribute to neurodevelopmental pathology in ADSLD and defective ciliogenesis may influence the ADSLD phenotypic spectrum.

CITE THIS COLLECTION

Stracker, Travis; Lüders, Jens; Dutto, Ilaria; Philipp, Melanie; pons, sebastian (2022): Source data supporting "Pathway specific effects of ADSL deficiency on neurodevelopment". Figshare+. Collection. https://doi.org/10.25452/figshare.plus.c.5793614
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FUNDING

COFUND BIST POSTDOCTORAL FELLOWSHIP PROGRAMME

European Commission

Marie Skłodowska-Curie grant agreement No. 754510

Ministry of Science, Innovation and Universities PGC2018-095616-B-I00

Ministry of Science, Innovation and Universities PGC2018-099562-B-I00

Ministry of Science, Innovation and Universities BFU2017-83562-P

Deutsche Forschungsgemeinschaft DFG PH144/4-1 and PH144/6-1

NIH Intramural Funding, National Cancer Institute

Research Institution(s)

NCI, Center for Cancer Research; Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology; University of Tübingen; Instituto de Biología Molecular de Barcelona; IBMB Barcelona

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