Loss of Lrp2 in zebrafish disrupts pronephric tubular clearance but not forebrain development
- 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.
- 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
- megalin, forebrain development, LDL receptor-related proteins, pronephros
- MeSH Terms
- Animals, Genetically Modified
- Body Patterning/genetics
- Body Patterning/physiology
- Gene Deletion
- Gene Expression Regulation, Developmental
- Kidney Tubules/embryology
- Kidney Tubules/metabolism*
- 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*
- Models, Biological
- Protein Structure, Tertiary
- Signal Transduction/genetics
- Signal Transduction/physiology
- 21455927 Full text @ Dev. Dyn.
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. (2011) Loss of Lrp2 in zebrafish disrupts pronephric tubular clearance but not forebrain development. Developmental Dynamics : an official publication of the American Association of Anatomists. 240(6):1567-1577.
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
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Engineered Foreign Genes