PUBLICATION

Loss of Lrp2 in zebrafish disrupts pronephric tubular clearance but not forebrain development

Authors

Kur, E., Christa, A., Veth, K.N., Gajera, C.R., Andrade-Navarro, M.A., Zhang, J., Willer, J.R., Gregg, R.G., Abdelilah-Seyfried, S., Bachmann, S., Link, B.A., Hammes, A., and Willnow, T.E.

ID

ZDB-PUB-110503-4

Date

2011

Source

Developmental Dynamics : an official publication of the American Association of Anatomists 240(6): 1567-1577 (Journal)

Registered Authors

Abdelilah-Seyfried, Salim, Gregg, Ronald G., Link, Brian, Veth, Kerry, Willer, Jason

Keywords

megalin, forebrain development, LDL receptor-related proteins, pronephros

MeSH Terms

Signal Transduction/genetics
Signal Transduction/physiology
Prosencephalon/embryology*
Prosencephalon/metabolism
Zebrafish/embryology*
Zebrafish/genetics
Zebrafish/metabolism
Zebrafish/physiology
Body Patterning/genetics
Body Patterning/physiology
Gene Expression Regulation, Developmental
Low Density Lipoprotein Receptor-Related Protein-2/chemistry
Low Density Lipoprotein Receptor-Related Protein-2/genetics*
Low Density Lipoprotein Receptor-Related Protein-2/metabolism
Low Density Lipoprotein Receptor-Related Protein-2/physiology
Metabolic Clearance Rate/genetics*
Kidney Tubules/embryology
Kidney Tubules/metabolism*
Phylogeny
Protein Structure, Tertiary
Gene Deletion
Animals, Genetically Modified
Animals
Models, Biological

(all 24)

PubMed

21455927 Full text @ Dev. Dyn.

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.

Genes / Markers

Figures

Show all Figures

Expression

Phenotype

Fish	Conditions	Stage	Phenotype	Figure
lrp2a^mw1/mw1	standard conditions	Prim-5	head morphology, normal	Fig. S5
lrp2a^mw1/mw1	standard conditions	Prim-5 to Protruding-mouth	forebrain development process quality, normal	Fig. 6
lrp2a^mw1/mw1	standard conditions	Prim-5 to Protruding-mouth	forebrain morphology, normal	Fig. 6
lrp2a^mw1/mw1	standard conditions	Prim-5 to Protruding-mouth	head morphology, normal	Fig. 6
lrp2a^mw1/mw1	standard conditions	Day 4	pronephric duct endosome absent, abnormal	Fig. 5
lrp2a^mw1/mw1	standard conditions	Day 4	pronephric duct recycling endosome membrane absent, abnormal	Fig. 5
lrp2a^mw1/mw1	standard conditions	Day 4	pronephros decreased functionality, abnormal	Fig. 4
lrp2a^mw1/mw1	standard conditions	Day 4	receptor-mediated endocytosis arrested, abnormal	Fig. 4
lrp2a^mw1/mw1	standard conditions	Day 4	renal absorption arrested, abnormal	Fig. 4
lrp2a^mw1/mw1	standard conditions	Adult	eye increased size, abnormal	Fig. 3

1 - 10 of 18

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Mutations / Transgenics

Allele	Construct	Type	Affected Genomic Region
mw1		Point Mutation	lrp2a
p5bnc		Point Mutation	lrp2a

Human Disease / Model

Sequence Targeting Reagents

Target	Reagent	Reagent Type
lrp2b	MO1-lrp2b	MRPHLNO
lrp2b	MO2-lrp2b	MRPHLNO
lrp2b	MO3-lrp2b	MRPHLNO

Fish

Fish
lrp2a^mw1/mw1
lrp2a^mw1/mw1 + MO1-lrp2b
lrp2a^mw1/mw1 + MO2-lrp2b
lrp2a^p5bnc/p5bnc
WT

Antibodies

Orthology

Gene	Orthology
lrp2a
lrp2b

Engineered Foreign Genes

Mapping

Kur et al., 2011 ZDB-PUB-110503-4 PMID:21455927

Loss of Lrp2 in zebrafish disrupts pronephric tubular clearance but not forebrain development

Kur et al., 2011

ZDB-PUB-110503-4
PMID:21455927