Unique Splicing of Lrp5 in the Brain : A New Player in Neurodevelopment and Brain Maturation
Luquero, Aureli (Institut de Recerca Sant Pau)
Pimentel, Noelia (Universitat de Barcelona)
Vilahur, Gemma (Institut de Recerca Sant Pau)
Badimon, Lina (Institut de Recerca Sant Pau)
Borrell-Pages, Maria (Institut de Recerca Sant Pau)
Universitat Autònoma de Barcelona

Fecha:	2024
Resumen:	Low-density lipoprotein receptor-related protein 5 (LRP5) is a constitutively expressed receptor with observed roles in bone homeostasis, retinal development, and cardiac metabolism. However, the function of LRP5 in the brain remains unexplored. This study investigates LRP5's role in the central nervous system by conducting an extensive analysis using RNA-seq tools and in silico assessments. Two protein-coding Lrp5 transcripts are expressed in mice: full-length Lrp5-201 and a truncated form encoded by Lrp5-202. Wt mice express Lrp5-201 in the liver and brain and do not express the truncated form. Lrp5 mice express Lrp5-202 in the liver and brain and do not express Lrp5-201 in the liver. Interestingly, Lrp5 mouse brains show full-length Lrp5-201 expression, suggesting that LRP5 has a role in preserving brain function during development. Functional gene enrichment analysis on RNA-seq unveils dysregulated expression of genes associated with neuronal differentiation and synapse formation in the brains of Lrp5 mice compared to Wt mice. Furthermore, Gene Set Enrichment Analysis highlights downregulated expression of genes involved in retinol and linoleic acid metabolism in Lrp5 mouse brains. Tissue-specific alternative splicing of Lrp5 in Lrp5 mice supports that the expression of LRP5 in the brain is needed for the correct synthesis of vitamins and fatty acids, and it is indispensable for correct brain development.
Ayudas:	Agencia Estatal de Investigación PID2019-107160RB-I00 Instituto de Salud Carlos III PMP22/00108 Ministerio de Economía y Competitividad CB16/11/00411
Derechos:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Lengua:	Anglès
Documento:	Article ; recerca ; Versió publicada
Materia:	LRP5 ; RNA-seq ; Brain ; Liver ; Retinoic acid ; Synapse ; Transcriptome
Publicado en:	International journal of molecular sciences, Vol. 25 Núm. 12 (june 2024) , p. 6763, ISSN 1422-0067

DOI: 10.3390/ijms25126763
PMID: 38928468

18 p, 1.8 MB

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