Axon fasciculation defects and retinal dysplasias in mice lacking the immunoglobulin superfamily adhesion molecule BEN/ALCAM/SC1
Department of Anatomy and Neurobiology, Washington University School of Medicine, St. Louis, MO 63110, USA. Molecular and Cellular Neuroscience
(Impact Factor: 3.84).
10/2004; 27(1):59-69. DOI: 10.1016/j.mcn.2004.06.005
The immunoglobulin superfamily adhesion molecule BEN (other names include ALCAM, SC1, DM-GRASP, neurolin, and CD166) has been implicated in the control of numerous developmental and pathological processes, including the guidance of retinal and motor axons to their targets. To test hypotheses about BEN function, we disrupted its gene via homologous recombination and analyzed the resulting mutant mice. Mice lacking BEN are viable and fertile, and display no external morphological defects. Despite grossly normal trajectories, both motor and retinal ganglion cell axons fasciculated poorly and were occasionally misdirected. In addition, BEN mutant retinae exhibited evaginated or invaginated regions with photoreceptor ectopias that resembled the "retinal folds" observed in some human retinopathies. Together, these results demonstrate that BEN promotes fasciculation of multiple axonal populations and uncover an unexpected function for BEN in retinal histogenesis.
Available from: onlinelibrary.wiley.com
- "In the retina, it was shown that several CAMs are essential for the correct extension of axons toward the exit point of the eye. Blocking the functions of L1, NrCAM or neurolin (also called BEN/DM- GRASP/ALCAM) leads to RGC axon fasciculation defects and subsequent errors in directed growth toward the optic disk (Brittis and Silver, 1995; Ott et al., 1998; Weiner et al., 2004). The next step of the RGC axons journey is the exit from the eye through the optic disk. "
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ABSTRACT: The formation of visual circuitry is a multi-step process that involves cell-cell interactions based on a range of molecular mechanisms. The correct implementation of individual events, including axon outgrowth and guidance, the formation of the topographic map, or the synaptic targeting of specific cellular subtypes, are prerequisites for a fully functional visual system that is able to appropriately process the information captured by the eyes. Cell adhesion molecules (CAMs) with their adhesive properties and their high functional diversity have been identified as key actors in several of these fundamental processes. Because of their growth-promoting properties, CAMs play an important role in neuritogenesis. Furthermore, they are necessary to control additional neurite development, regulating dendritic spacing and axon pathfinding. Finally, trans-synaptic interactions of CAMs ensure cell type-specific connectivity as a basis for the establishment of circuits processing distinct visual features. Recent discoveries implicating CAMs in novel mechanisms have led to a better general understanding of neural circuit formation, but also revealed an increasing complexity of their function. This review aims at describing the different levels of action for CAMs in order to shape neural connectivity, with a special focus on the visual system. This article is protected by copyright. All rights reserved.
Copyright © 2015 Wiley Periodicals, Inc., a Wiley company.
Developmental Neurobiology 02/2015; 75(6). DOI:10.1002/dneu.22267 · 3.37 Impact Factor
Available from: Fabien Sohet
- "For instance, Th17 cells express MCAM which binds to laminin 411 on the EC basement membrane , CD4+ lymphocytes express CD6 which binds to EC ALCAM , and ninjurin-1 on myeloid cells homotypically interacts with ninjurin-1 on inflamed ECs . Mouse knockouts for Alcam and Mcam (Mcamtm1Lex) have been generated, however these knockout models have not been extensively utilized to study neurological disease. "
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ABSTRACT: The blood–brain barrier (BBB) is a complex physiological structure formed
by the blood vessels of the central nervous system (CNS) that tightly regulates
the movement of substances between the blood and the neural tissue. Recently,
the generation and analysis of different genetic mouse models has allowed for
greater understanding of BBB development, how the barrier is regulated during
health and its response to disease. Here we discuss: 1) Genetic mouse models
that have been used to study the BBB, 2) Available mouse genetic tools that can
aid in the study of the BBB, and 3) Potential tools that if generated could
greatly aid in our understanding of the BBB.
Fluids and Barriers of the CNS 01/2013; 10(1):3. DOI:10.1186/2045-8118-10-3
Available from: Jing Jiao
- "Genetic deletion of CD166 gene was achieved by replacing its first exon with a cDNA encoding EGFP . CD166 null mice are phenotypically normal and fertile . We examined the prostate at 8 and 20 weeks of age and found no difference in gross anatomy and histology among WT (data not shown), CD166+/− and CD166−/− mouse prostates (Figure 5A). "
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ABSTRACT: New therapies for late stage and castration resistant prostate cancer (CRPC) depend on defining unique properties and pathways of cell sub-populations capable of sustaining the net growth of the cancer. One of the best enrichment schemes for isolating the putative stem/progenitor cell from the murine prostate gland is Lin(-);Sca1(+);CD49f(hi) (LSC(hi)), which results in a more than 10-fold enrichment for in vitro sphere-forming activity. We have shown previously that the LSC(hi) subpopulation is both necessary and sufficient for cancer initiation in the Pten-null prostate cancer model. To further improve this enrichment scheme, we searched for cell surface molecules upregulated upon castration of murine prostate and identified CD166 as a candidate gene. CD166 encodes a cell surface molecule that can further enrich sphere-forming activity of WT LSC(hi) and Pten null LSC(hi). Importantly, CD166 could enrich sphere-forming ability of benign primary human prostate cells in vitro and induce the formation of tubule-like structures in vivo. CD166 expression is upregulated in human prostate cancers, especially CRPC samples. Although genetic deletion of murine CD166 in the Pten null prostate cancer model does not interfere with sphere formation or block prostate cancer progression and CRPC development, the presence of CD166 on prostate stem/progenitors and castration resistant sub-populations suggest that it is a cell surface molecule with the potential for targeted delivery of human prostate cancer therapeutics.
PLoS ONE 08/2012; 7(8):e42564. DOI:10.1371/journal.pone.0042564 · 3.23 Impact Factor
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