LRT, a tendon-specific leucine-rich repeat protein, promotes muscle-tendon targeting through its interaction with Robo

Wayburn, Bess; Volk, Talila

doi:10.1242/dev.040329

Cited by 41 publications

(38 citation statements)

References 29 publications

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“…Several genes involved in muscle targeting to tendon cells are positively regulated by Stripe activity in the embryo, including slit, Thrombospondin (Tsp), Leucine-rich tendon-specific protein (Lrt) and slowdown (slow) (Chanana et al, 2009;Gilsohn and Volk, 2010a;Gilsohn and Volk, 2010b;Kramer et al, 2001;Subramanian et al, 2007;Wayburn and Volk, 2009). Interestingly, although Stripe is sufficient to induce their expression, some of these genes are expressed at low level even in stripe mutant embryos, raising the possibility that segment polarity genes, such as hh, wg, or both, initially activate a set of tendon-specific genes, including stripeB.…”

Section: Early Tendon Determination Is Independent Of Muscle Cellsmentioning

confidence: 99%

Connecting muscles to tendons: tendons and musculoskeletal development in flies and vertebrates

2010

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There was an error published in Development 137, 2807-2817.On p. 2808, StripeB was incorrectly referred to as an epidermal growth factor (Egf)-like, rather than an early growth response (Egr)-like, transcription factor. The corrected sentence appears below.One of the earliest genes that induce tendon progenitor cells within the ectoderm encodes the early growth response (Egr)-like transcription factor StripeB, one of the two isoforms produced by the stripe gene.We apologise to the authors and readers for this mistake. SummaryThe formation of the musculoskeletal system represents an intricate process of tissue assembly involving heterotypic inductive interactions between tendons, muscles and cartilage. An essential component of all musculoskeletal systems is the anchoring of the force-generating muscles to the solid support of the organism: the skeleton in vertebrates and the exoskeleton in invertebrates. Here, we discuss recent findings that illuminate musculoskeletal assembly in the vertebrate embryo, findings that emphasize the reciprocal interactions between the forming tendons, muscle and cartilage tissues. We also compare these events with those of the corresponding system in the Drosophila embryo, highlighting distinct and common pathways that promote efficient locomotion while preserving the form of the organism.

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Section: Early Tendon Determination Is Independent Of Muscle Cellsmentioning

confidence: 99%

Connecting muscles to tendons: tendons and musculoskeletal development in flies and vertebrates

2010

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“…In Caenorhabditis elegans, SLT-1/Slit also binds to the EVA-1 transmembrane protein that has homologues in mammals (Fujisawa et al, 2007). Likewise, biochemical and genetic data demonstrate that an interaction occurs between the LRR tendon-specific protein (LRT) and Robo, highlighting a mechanism by which LRT can modulate Robo-Slit interactions and influence muscle cell migration (Wayburn and Volk, 2009). Moreover, as we discuss below, several studies have identified HSPGs as co-receptors for Slits that are necessary for Slit-Robo signalling (Hu, 2001;Steigemann et al, 2004).…”

Section: Reviewmentioning

confidence: 99%

Moving away from the midline: new developments for Slit and Robo

2010

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SummaryIn most tissues, the precise control of cell migration and cellcell interaction is of paramount importance to the development of a functional structure. Several families of secreted molecules have been implicated in regulating these aspects of development, including the Slits and their Robo receptors. These proteins have well described roles in axon guidance but by influencing cell polarity and adhesion, they participate in many developmental processes in diverse cell types. We review recent progress in understanding both the molecular mechanisms that modulate Slit/Robo expression and their functions in neural and non-neural tissue. Key words: Axon guidance, Cell migration, Cell-cell interaction IntroductionIn most organisms, the central nervous system (CNS) develops along a bilateral axis of symmetry located at the midline (Placzek and Briscoe, 2005). During development, the ventral midline or floor plate acts as an organiser through the secretion of diffusible proteins (Placzek and Briscoe, 2005;Gore et al., 2008), which control the growth of axons and dendrites and the migration of neurons across the midline. In the forebrain, glial or neuronal cells delineate the midline (see Glossary, Box 1) and also control axon guidance. For more than two decades, many developmental neurobiologists have tried to understand the mechanisms that control midline crossing in the CNS and to answer some key questions. Firstly, how are commissural axons (see Glossary, Box 1) attracted to the midline and how do their growth cones (see Glossary, Box1) receive and integrate the multiple and contrasting signals released by midline cells? Secondly, what are the molecular and signalling changes that enable commissural axons to leave the midline and often to switch to a longitudinal growth mode? All midline-derived axon guidance factors are expressed at other locations in many developing and mature tissues, where they control a wide range of biological processes.Roundabout receptors (Robo) and their Slit ligands form one of the most crucial ligand-receptor pairings among the axon guidance molecules. Robos were identified in Drosophila in a mutant screen for genes that control the midline crossing of commissural axons (Kidd et al., 1998;Seeger et al., 1993). Similarly, Slit was discovered in Drosophila as a protein secreted by midline glia (Rothberg et al., 1988;Rothberg et al., 1990). Homologues of both proteins have since been discovered in many species (for a review, see . However, the Slit/Robo couple not only functions in axon guidance but also in a variety of developmental Development 137, 1939Development 137, -1952Development 137, (2010 Commissural axons Axons with cell bodies (somata) located on one side of the central nervous system (CNS) that project axons across the midline to contact target cells on the opposite side. Growth cone A specialised bulbous enlargement at the end of growing axons that is characterised by dynamic filamentous extensions, known as filopodia. They sense the environment and respond to adhesi...

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“…Slit has been described previously to function in Drosophila muscle migration (Kramer et al, 2001;Wayburn and Volk, 2009). Slit is expressed by tendon cells and has been shown to exhibit dual and opposite activities.…”

Section: Introductionmentioning

confidence: 99%

Slit cleavage is essential for producing an active, stable, non-diffusible short-range signal that guides muscle migration

et al. 2015

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During organogenesis, secreted signaling proteins direct cell migration towards their target tissue. In Drosophila embryos, developing muscles are guided by signals produced by tendons to promote the proper attachment of muscles to tendons, essential for proper locomotion. Previously, the repulsive protein Slit, secreted by tendon cells, has been proposed to be an attractant for muscle migration. However, our findings demonstrate that through tight control of its distribution, Slit repulsion is used for both directing and arresting muscle migration. We show that Slit cleavage restricts its distribution to tendon cells, allowing it to function as a short-range repellent that directs muscle migration and patterning, and promotes their halt upon reaching the target site. Mechanistically, we show that Slit processing produces a rapidly degraded C-terminal fragment and an active, stable N-terminal polypeptide that is tethered to the tendon cell membrane, which further protects it from degradation. Consistently, the requirement for Slit processing can be bypassed by providing an uncleavable, membrane-bound form of Slit that is stable and is retained on expressing tendon cells. Moreover, muscle elongation appears to be extremely sensitive to Slit levels, as replacing the entire full-length Slit with the stable Slit-N-polypeptide results in excessive repulsion, which leads to a defective muscle pattern. These findings reveal a novel cleavage-dependent regulatory mechanism controlling Slit spatial distribution, which may operate in other Slit-dependent processes.

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LRT, a tendon-specific leucine-rich repeat protein, promotes muscle-tendon targeting through its interaction with Robo

Cited by 41 publications

References 29 publications

Connecting muscles to tendons: tendons and musculoskeletal development in flies and vertebrates

Connecting muscles to tendons: tendons and musculoskeletal development in flies and vertebrates

Moving away from the midline: new developments for Slit and Robo

Slit cleavage is essential for producing an active, stable, non-diffusible short-range signal that guides muscle migration

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