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Molecular mechanisms of tiling and self-avoidance in neural development.

Cameron S, Rao Y - Mol Brain (2010)

Bottom Line: Dscams and Turtle (Tutl), two Ig superfamily proteins, have been shown to mediate contact-dependent homotypic interactions in tiling and self-avoidance.By contrast, the Activin pathway regulates axonal tiling in a contact-independent manner.These cell surface signals may directly or indirectly regulate the activity of the Tricornered kinase pathway and/or other intracellular signaling pathways to prevent the overlap between same-type neuronal arbors in the sensory or synaptic input field.

View Article: PubMed Central - HTML - PubMed

Affiliation: McGill Centre for Research in Neuroscience, McGill University Health Centre, 1650 Cedar Avenue, Montreal, Quebec H3G 1A4, Canada.

ABSTRACT
Recent studies have begun to unravel the molecular basis of tiling and self-avoidance, two important cellular mechanisms that shape neuronal circuitry during development in both invertebrates and vertebrates. Dscams and Turtle (Tutl), two Ig superfamily proteins, have been shown to mediate contact-dependent homotypic interactions in tiling and self-avoidance. By contrast, the Activin pathway regulates axonal tiling in a contact-independent manner. These cell surface signals may directly or indirectly regulate the activity of the Tricornered kinase pathway and/or other intracellular signaling pathways to prevent the overlap between same-type neuronal arbors in the sensory or synaptic input field.

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Proposed models for the action of Drosophila and vertebrate Dscams. A, Drosophila Dscam1 mediates homotypic repulsion in tiling and self-avoidance. The homophilic binding specificity of Dscam1 is determined by its Ig2 (red), Ig3 (green) and Ig7 (purple) domains. Half of Ig2, half of Ig3, and entire Ig7 domains are encoded by one of 12, 48, and 33 alternative exons, respectively. Thus, the extensive alternative splicing can generate 19,008 Dscam1 isoforms with different binding specificity. The binding between two Dscam isoforms only occurs if all three Ig domains (i.e. Ig2, Ig3 and Ig7) are identical. B, Vertebrate Dscams may mediate de-adhesion in tiling and self-avoidance by down-regulating the function of some unknown cell-type-specific adhesion molecules. The binding region on vertebrate Dscams is unknown, and presumably contains one or more of Ig domains. Circles, Ig domains. Rectangles, fibronectin type-III repeats. PM, plasma membrane
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Figure 2: Proposed models for the action of Drosophila and vertebrate Dscams. A, Drosophila Dscam1 mediates homotypic repulsion in tiling and self-avoidance. The homophilic binding specificity of Dscam1 is determined by its Ig2 (red), Ig3 (green) and Ig7 (purple) domains. Half of Ig2, half of Ig3, and entire Ig7 domains are encoded by one of 12, 48, and 33 alternative exons, respectively. Thus, the extensive alternative splicing can generate 19,008 Dscam1 isoforms with different binding specificity. The binding between two Dscam isoforms only occurs if all three Ig domains (i.e. Ig2, Ig3 and Ig7) are identical. B, Vertebrate Dscams may mediate de-adhesion in tiling and self-avoidance by down-regulating the function of some unknown cell-type-specific adhesion molecules. The binding region on vertebrate Dscams is unknown, and presumably contains one or more of Ig domains. Circles, Ig domains. Rectangles, fibronectin type-III repeats. PM, plasma membrane

Mentions: The first clue for a cell surface recognition mechanism underlying tiling and self-avoidance came from recent studies on the Down's syndrome cell adhesion molecule Dscam [24]. Dscam belongs to the immunoglobulin superfamily, and consists of ten Ig-like domains, six fibronectin type-III repeats, a singe transmembrane region and a cytoplasmic domain [25] (Fig. 2). There are two Dscam genes (i.e. Dscam and Dscam-like or DscamL1) in vertebrates [26], and four Dscam genes (Dscam 1-4) in Drosophila melanogaster [27,28]. Both invertebrate and vertebrate Dscams mediate homophilic binding [29-31] (Fig. 2). In Drosophila, the Dscam1 gene has the potential to generate a large number of isoforms (i.e. 38,016) that possess 19,008 different binding specificities through alternative splicing [27]. In vitro studies demonstrate that each isoform binds to itself but shows little binding to a different isoform [29,32] (Fig. 2).


Molecular mechanisms of tiling and self-avoidance in neural development.

Cameron S, Rao Y - Mol Brain (2010)

Proposed models for the action of Drosophila and vertebrate Dscams. A, Drosophila Dscam1 mediates homotypic repulsion in tiling and self-avoidance. The homophilic binding specificity of Dscam1 is determined by its Ig2 (red), Ig3 (green) and Ig7 (purple) domains. Half of Ig2, half of Ig3, and entire Ig7 domains are encoded by one of 12, 48, and 33 alternative exons, respectively. Thus, the extensive alternative splicing can generate 19,008 Dscam1 isoforms with different binding specificity. The binding between two Dscam isoforms only occurs if all three Ig domains (i.e. Ig2, Ig3 and Ig7) are identical. B, Vertebrate Dscams may mediate de-adhesion in tiling and self-avoidance by down-regulating the function of some unknown cell-type-specific adhesion molecules. The binding region on vertebrate Dscams is unknown, and presumably contains one or more of Ig domains. Circles, Ig domains. Rectangles, fibronectin type-III repeats. PM, plasma membrane
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2959082&req=5

Figure 2: Proposed models for the action of Drosophila and vertebrate Dscams. A, Drosophila Dscam1 mediates homotypic repulsion in tiling and self-avoidance. The homophilic binding specificity of Dscam1 is determined by its Ig2 (red), Ig3 (green) and Ig7 (purple) domains. Half of Ig2, half of Ig3, and entire Ig7 domains are encoded by one of 12, 48, and 33 alternative exons, respectively. Thus, the extensive alternative splicing can generate 19,008 Dscam1 isoforms with different binding specificity. The binding between two Dscam isoforms only occurs if all three Ig domains (i.e. Ig2, Ig3 and Ig7) are identical. B, Vertebrate Dscams may mediate de-adhesion in tiling and self-avoidance by down-regulating the function of some unknown cell-type-specific adhesion molecules. The binding region on vertebrate Dscams is unknown, and presumably contains one or more of Ig domains. Circles, Ig domains. Rectangles, fibronectin type-III repeats. PM, plasma membrane
Mentions: The first clue for a cell surface recognition mechanism underlying tiling and self-avoidance came from recent studies on the Down's syndrome cell adhesion molecule Dscam [24]. Dscam belongs to the immunoglobulin superfamily, and consists of ten Ig-like domains, six fibronectin type-III repeats, a singe transmembrane region and a cytoplasmic domain [25] (Fig. 2). There are two Dscam genes (i.e. Dscam and Dscam-like or DscamL1) in vertebrates [26], and four Dscam genes (Dscam 1-4) in Drosophila melanogaster [27,28]. Both invertebrate and vertebrate Dscams mediate homophilic binding [29-31] (Fig. 2). In Drosophila, the Dscam1 gene has the potential to generate a large number of isoforms (i.e. 38,016) that possess 19,008 different binding specificities through alternative splicing [27]. In vitro studies demonstrate that each isoform binds to itself but shows little binding to a different isoform [29,32] (Fig. 2).

Bottom Line: Dscams and Turtle (Tutl), two Ig superfamily proteins, have been shown to mediate contact-dependent homotypic interactions in tiling and self-avoidance.By contrast, the Activin pathway regulates axonal tiling in a contact-independent manner.These cell surface signals may directly or indirectly regulate the activity of the Tricornered kinase pathway and/or other intracellular signaling pathways to prevent the overlap between same-type neuronal arbors in the sensory or synaptic input field.

View Article: PubMed Central - HTML - PubMed

Affiliation: McGill Centre for Research in Neuroscience, McGill University Health Centre, 1650 Cedar Avenue, Montreal, Quebec H3G 1A4, Canada.

ABSTRACT
Recent studies have begun to unravel the molecular basis of tiling and self-avoidance, two important cellular mechanisms that shape neuronal circuitry during development in both invertebrates and vertebrates. Dscams and Turtle (Tutl), two Ig superfamily proteins, have been shown to mediate contact-dependent homotypic interactions in tiling and self-avoidance. By contrast, the Activin pathway regulates axonal tiling in a contact-independent manner. These cell surface signals may directly or indirectly regulate the activity of the Tricornered kinase pathway and/or other intracellular signaling pathways to prevent the overlap between same-type neuronal arbors in the sensory or synaptic input field.

Show MeSH
Related in: MedlinePlus