|
|
|
|
|
|
|
||||
| Home Help Feedback Subscriptions Archive Search Table of Contents | ||||
First published online December 28, 2004
doi: 10.1242/10.1242/dev.01580
Max-Delbrueck-Center for Molecular Medicine, Berlin, 13092, Germany
Author for correspondence (e-mail:
willnow{at}mdc-berlin.de)
Accepted 10 November 2004
Megalin is a low-density lipoprotein receptor-related protein (LRP2) expressed in the neuroepithelium and the yolk sac of the early embryo. Absence of megalin expression in knockout mice results in holoprosencephaly, indicating an essential yet unidentified function in forebrain development. We used mice with complete or conditional megalin gene inactivation in the embryo to demonstrate that expression of megalin in the neuroepithelium but not in the yolk sac is crucial for brain development. During early forebrain development, megalin deficiency leads to an increase in bone morphogenic protein (Bmp) 4 expression and signaling in the rostral dorsal neuroepithelium, and a subsequent loss of sonic hedgehog (Shh) expression in the ventral forebrain. As a consequence of absent SHH activity, ventrally derived oligodendroglial and interneuronal cell populations are lost in the forebrain of megalin–/– embryos. Similar defects are seen in models with enhanced signaling through BMPs, central regulators of neural tube patterning. Because megalin mediates endocytic uptake and degradation of BMP4, these findings indicate a role for megalin in neural tube specification, possibly by acting as BMP4 clearance receptor in the neuroepithelium.
Key words: LDL receptor-related proteins, Bone morphogenic proteins, Sonic hedgehog, Yolk sac, Holoprosencephaly, Mouse, LRP2
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati 
Twitter What's this?
This article has been cited by other articles:
|
|
 |
|
  C. E. Fleming, F. M. Mar, F. Franquinho, M. J. Saraiva, and M. M. Sousa Transthyretin Internalization by Sensory Neurons Is Megalin Mediated and Necessary for Its Neuritogenic Activity J. Neurosci., March 11, 2009; 29(10): 3220 - 3232. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Warr, N. Powles-Glover, A. Chappell, J. Robson, D. Norris, and R. M. Arkell Zic2-associated holoprosencephaly is caused by a transient defect in the organizer region during gastrulation Hum. Mol. Genet., October 1, 2008; 17(19): 2986 - 2996. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Li, R. Cong, and D. Biemesderfer The COOH terminus of megalin regulates gene expression in opossum kidney proximal tubule cells Am J Physiol Cell Physiol, August 1, 2008; 295(2): C529 - C537. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. D. Upton, L. Long, R. C. Trembath, and N. W. Morrell Functional Characterization of Bone Morphogenetic Protein Binding Sites and Smad1/5 Activation in Human Vascular Cells Mol. Pharmacol., February 1, 2008; 73(2): 539 - 552. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Fernandes, G. Gutin, H. Alcorn, S. K. McConnell, and J. M. Hebert Mutations in the BMP pathway in mice support the existence of two molecular classes of holoprosencephaly Development, November 1, 2007; 134(21): 3789 - 3794. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. E. Willnow, A. Hammes, and S. Eaton Lipoproteins and their receptors in embryonic development: more than cholesterol clearance Development, September 15, 2007; 134(18): 3239 - 3249. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Vaillant, O. Michos, S. Orolicki, F. Brellier, S. Taieb, E. Moreno, H. Te, R. Zeller, and D. Monard Protease nexin 1 and its receptor LRP modulate SHH signalling during cerebellar development Development, May 1, 2007; 134(9): 1745 - 1754. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. D. Weatherbee, K. V. Anderson, and L. A. Niswander LDL-receptor-related protein 4 is crucial for formation of the neuromuscular junction. Development, December 1, 2006; 133(24): 4993 - 5000. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. R. Morales, J. Zeng, M. El Alfy, J. L. Barth, M. R. Chintalapudi, R. A. McCarthy, J. P. Incardona, and W. S. Argraves Epithelial Trafficking of Sonic Hedgehog By Megalin J. Histochem. Cytochem., October 1, 2006; 54(10): 1115 - 1127. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Pan, L. Zhu, Y. Deng, and J. W. Pollard Microarray Analysis of Uterine Epithelial Gene Expression during the Implantation Window in the Mouse Endocrinology, October 1, 2006; 147(10): 4904 - 4916. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Mar and P. A. Hoodless Embryonic fibroblasts from mice lacking tgif were defective in cell cycling. Mol. Cell. Biol., June 1, 2006; 26(11): 4302 - 4310. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Li, H. Zhang, Y. Litingtung, and C. Chiang Cholesterol modification restricts the spread of Shh gradient in the limb bud PNAS, April 25, 2006; 103(17): 6548 - 6553. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. B. Johnson, R. E. Hammer, and J. Herz Abnormal development of the apical ectodermal ridge and polysyndactyly in Megf7-deficient mice Hum. Mol. Genet., November 15, 2005; 14(22): 3523 - 3538. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. E. Maurer and J. A. Cooper Endocytosis of megalin by visceral endoderm cells requires the Dab2 adaptor protein J. Cell Sci., November 15, 2005; 118(22): 5345 - 5355. [Abstract] [Full Text] [PDF]
|
|
