title: Loss of Lrp2 in zebrafish disrupts pronephric tubular clearance but not forebrain development.
abstract: Low-density lipoprotein receptor-related protein 2 (LRP2) is a multifunctional cell surface receptor conserved from nematodes to humans. In mammals, it acts as regulator of sonic hedgehog and bone morphogenetic protein pathways in patterning of the embryonic forebrain and as a clearance receptor in the adult kidney. Little is known about activities of this LRP in other phyla. Here, we extend the functional elucidation of LRP2 to zebrafish as a model organism of receptor (dys)function. We demonstrate that expression of Lrp2 in embryonic and larval fish recapitulates the patterns seen in mammalian brain and kidney. Furthermore, we studied the consequence of receptor deficiencies in lrp2 and in lrp2b, a homologue unique to fish, using ENU mutagenesis or morpholino knockdown. While receptor-deficient zebrafish suffer from overt renal resorption deficiency, their brain development proceeds normally, suggesting evolutionary conservation of receptor functions in pronephric duct clearance but not in patterning of the teleost forebrain.
authors: Max-Delbrück-Center for Molecular Medicine, Universitätsmedizin, Berlin, Germany.
authors: Esther
authors: E
authors: Kur
authors: Anna
authors: A
authors: Christa
authors: Kerry N
authors: KN
authors: Veth
authors: Chandresh R
authors: CR
authors: Gajera
authors: Miguel A
authors: MA
authors: Andrade-Navarro
authors: Jingjing
authors: J
authors: Zhang
authors: Jason R
authors: JR
authors: Willer
authors: Ronald G
authors: RG
authors: Gregg
authors: Salim
authors: S
authors: Abdelilah-Seyfried
authors: Sebastian
authors: S
authors: Bachmann
authors: Brian A
authors: BA
authors: Link
authors: Annette
authors: A
authors: Hammes
authors: Thomas E
authors: TE
authors: Willnow
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D019521:Body Patterning / Q000235:genetics / Q000502:physiology; D017353:Gene Deletion; D018507:Gene Expression Regulation, Developmental; D007684:Kidney Tubules / Q000196:embryology / Q000378:metabolism*; D026561:Low Density Lipoprotein Receptor-Related Protein-2 / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D008657:Metabolic Clearance Rate / Q000235:genetics*; D008954:Models, Biological; D010802:Phylogeny; D016548:Prosencephalon / Q000196:embryology* / Q000378:metabolism; D017434:Protein Structure, Tertiary; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology; D015027:Zebrafish / Q000196:embryology* / Q000235:genetics / Q000378:metabolism / Q000502:physiology
chemical_list: D026561:Low Density Lipoprotein Receptor-Related Protein-2