1015 Axon patterning requires DN-cadherin, a novel neuronal adhesion receptor, in the drosophila embryonic CNS

Iwai, Yoshio; Usui, Tadao; Hirano, Shinji; Steward, Ruth; Takeichi, Masatoshi; Uemura, Tadashi

doi:10.1016/s0168-0102(97)90320-5

Cited by 98 publications

(171 citation statements)

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“…Motor axons expressing beaten path extend along a pathway that expresses sidestep, and mutations in either molecular component can disrupt axon pathfinding (Siebert et al 2009). Loss of DN-Cadherin in fly embryos induces defasciculation and misorientation of axons (Iwai et al 1997). In null mouse mutants of Celsr3, an atypical cadherin/Drosophila flamingo homologue, the extension of subcortical projections to and within the cortex are impaired and cortex-specific inactivation impairs projections to the cortex (Zhou et al 2008).…”

Section: Adhesive Cuesmentioning

confidence: 99%

Cellular Strategies of Axonal Pathfinding

Raper

Mason

2010

Cold Spring Harbor Perspectives in Biology

157

130

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Axons follow highly stereotyped and reproducible trajectories to their targets. In this review we address the properties of the first pioneer neurons to grow in the developing nervous system and what has been learned over the past several decades about the extracellular and cell surface substrata on which axons grow. We then discuss the types of guidance cues and their receptors that influence axon extension, what determines where cues are expressed, and how axons respond to the cues they encounter in their environment.T his article provides an overview of how growth cones respond to the cellular substrata and molecular cues they encounter as they extend through the developing nervous system. It elaborates on the primer by Kolodkin and TessierLavigne (2010) and touches on many of the topics covered in greater detail in the articles that follow. The first sections describe how axons extend in a directed manner, the substrata on which they grow, interactions between pioneer and follower axons, and growth cone behaviors in emerging tracts and at decision points. The subsequent sections discuss examples of specific cues, their distributions, how their distributions are determined, and how growth cones integrate multiple cues during pathfinding. AXONS EXTEND IN VIVO IN A DIRECTED MANNERThe first person to visualize the growing tips of axons, Ramon y Cajal, recognized that axons for the most part grow very efficiently towards their ultimate targets. He was a strong advocate for axons finding their way in response to chemotactic cues:"If one admits that neuroblasts are endowed with chemotactic properties, then one might also imagine that they are capable of ameboid movements, initiated by factors secreted from epithelial, neural, or mesodermal elements. As a result, their processes may be oriented in the direction of chemical gradients, and thus guided to the secreting cells" (Ramon y Cajal 1892; trans. English, 1995).This surprisingly modern outlook emphasizing directed guidance was temporarily derailed by the views of Weiss during the 1920s and 1930s. He first argued that functional specificity did not arise as a consequence of specific axonal connections (Weiss 1936), and later argued that nonspecific mechanical guidance cues play a predominant role in guiding axons and organizing them into nerves and tracts

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Section: Adhesive Cuesmentioning

confidence: 99%

Cellular Strategies of Axonal Pathfinding

Raper

Mason

2010

Cold Spring Harbor Perspectives in Biology

157

130

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“…If cadherins are inactivated in tissues, their cell±cell association becomes unstabilized, leading to disassembly of the multicellular system. In the case of neurones, neurite outgrowth and their fasciculation are impaired by inactivation of cadherins (Inoue & Sanes 1997;Iwai et al 1997). However, the functions of the synaptically localized cadherins are little understood.…”

Section: Introductionmentioning

confidence: 99%

Blockade of cadherin‐6B activity perturbs the distribution of PSD‐95 family proteins in retinal neurones

2000

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“…The EC domains identified in the region preceding the cleavage site were assigned negative number identifiers (EC-3', EC-2', and EC-1') to indicate their likely absence from the mature protein. The hypothesis that DN-cadherin proprotein is cleaved by a subtilisin-like convertase is supported by the work of Iwai and colleagues, which identified two distinct DN-cadherin species in the lysates of embryos and S2 cells transfected with a DN-cadherin encoding cDNA construct (14). The approximate molecular mass of the dominant species is 300 kD, consistent with the calculated mass of DN-cadherin regions C-terminal to the predicted furin cleavage site, while the second species is approximately 330 kD, consistent with the molecular mass of the uncleaved form (14).…”

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confidence: 97%

“…Analysis of the Drosophila genome has revealed 17 genes that encode proteins containing EC-like domains (12). Three of these molecules, DN-cadherin encoded by CadN, DEcadherin encoded by Shg, and DN-cad2 encoded by CadN2, which appears likely to be a partial duplication product of the CadN gene, contain catenin binding sites in their cytoplasmic regions, and have been shown to interact with the Drosophila β-catenin homolog armadillo (12)(13)(14). DN-and DE-cadherins serve cell adhesion and tissue patterning functions analogous to their vertebrate counterparts (13,14).…”

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confidence: 99%

“…Three of these molecules, DN-cadherin encoded by CadN, DEcadherin encoded by Shg, and DN-cad2 encoded by CadN2, which appears likely to be a partial duplication product of the CadN gene, contain catenin binding sites in their cytoplasmic regions, and have been shown to interact with the Drosophila β-catenin homolog armadillo (12)(13)(14). DN-and DE-cadherins serve cell adhesion and tissue patterning functions analogous to their vertebrate counterparts (13,14). Also, like vertebrate classical cadherins, overexpression of DN-cadherin or DE-cadherin in otherwise nonadhesive cells induces Ca 2þ -dependent cell aggregation (13,15).…”

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Crystal structures of Drosophila N-cadherin ectodomain regions reveal a widely used class of Ca ²⁺ -free interdomain linkers

Jin

Walker

Felsövályi

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

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Vertebrate classical cadherins mediate selective calcium-dependent cell adhesion by mechanisms now understood at the atomic level. However, structures and adhesion mechanisms of cadherins from invertebrates, which are highly divergent yet function in similar roles, remain unknown. Here we present crystal structures of three-and four-tandem extracellular cadherin (EC) domain segments from Drosophila N-cadherin (DN-cadherin), each including the predicted N-terminal EC1 domain (denoted EC1') of the mature protein. While the linker regions for the EC1'-EC2' and EC3'-EC4' pairs display binding of three Ca 2 ions similar to that of vertebrate cadherins, domains EC2' and EC3' are joined in a "kinked" orientation by a previously uncharacterized Ca 2 -free linker. Biophysical analysis demonstrates that a construct containing the predicted N-terminal nine EC domains of DN-cadherin forms homodimers with affinity similar to vertebrate classical cadherins, whereas deleting the ninth EC domain ablates dimerization. These results suggest that, unlike their vertebrate counterparts, invertebrate cadherins may utilize multiple EC domains to form intercellular adhesive bonds. Sequence analysis reveals that similar Ca 2 -free linkers are widely distributed in the ectodomains of both vertebrate and invertebrate cadherins.

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1015 Axon patterning requires DN-cadherin, a novel neuronal adhesion receptor, in the drosophila embryonic CNS

Cited by 98 publications

References 0 publications

Cellular Strategies of Axonal Pathfinding

Cellular Strategies of Axonal Pathfinding

Blockade of cadherin‐6B activity perturbs the distribution of PSD‐95 family proteins in retinal neurones

Crystal structures of Drosophila N-cadherin ectodomain regions reveal a widely used class of Ca ²⁺ -free interdomain linkers

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1015 Axon patterning requires DN-cadherin, a novel neuronal adhesion receptor, in the drosophila embryonic CNS

Cited by 98 publications

References 0 publications

Cellular Strategies of Axonal Pathfinding

Cellular Strategies of Axonal Pathfinding

Blockade of cadherin‐6B activity perturbs the distribution of PSD‐95 family proteins in retinal neurones

Crystal structures of Drosophila N-cadherin ectodomain regions reveal a widely used class of Ca 2+ -free interdomain linkers

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Crystal structures of Drosophila N-cadherin ectodomain regions reveal a widely used class of Ca ²⁺ -free interdomain linkers