Hedgehog signalling acts upstream of Laminin alpha1 transcription in the zebrafish paraxial mesoderm

Pickering, Joseph; Cunliffe, Vincent T.; Eeden, Freek van; Borycki, Anne‐Gaëlle

doi:10.1016/j.matbio.2016.11.004

Cited by 11 publications

(5 citation statements)

References 72 publications

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“…During embryogenesis, Sonic hedgehog signalling regulates basement membrane components, such as laminin-111 54 – 56 . This is crucial for myotome formation and basement membranes are disrupted in the TA 3 mutant 13 .…”

Section: Discussionmentioning

confidence: 99%

Absence of the primary cilia formation gene Talpid3 impairs muscle stem cell function

Martinez-Heredia,

Blackwell,

Sebastian

et al. 2023

Commun Biol

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Skeletal muscle stem cells (MuSC) are crucial for tissue homoeostasis and repair after injury. Following activation, they proliferate to generate differentiating myoblasts. A proportion of cells self-renew, re-enter the MuSC niche under the basal lamina outside the myofiber and become quiescent. Quiescent MuSC have a primary cilium, which is disassembled upon cell cycle entry. Ex vivo experiments suggest cilia are important for MuSC self-renewal, however, their requirement for muscle regeneration in vivo remains poorly understood. Talpid3 (TA3) is essential for primary cilia formation and Hedgehog (Hh) signalling. Here we use tamoxifen-inducible conditional deletion of TA3 in MuSC (iSC-KO) and show that regeneration is impaired in response to cytotoxic injury. Depletion of MuSC after regeneration suggests impaired self-renewal, also consistent with an exacerbated phenotype in TA3iSC-KO mice after repeat injury. Single cell transcriptomics of MuSC progeny isolated from myofibers identifies components of several signalling pathways, which are deregulated in absence of TA3, including Hh and Wnt. Pharmacological activation of Wnt restores muscle regeneration, while purmorphamine, an activator of the Smoothened (Smo) co-receptor in the Hh pathway, has no effect. Together, our data show that TA3 and primary cilia are important for MuSC self-renewal and pharmacological treatment can efficiently restore muscle regeneration.

show abstract

Section: Discussionmentioning

confidence: 99%

Absence of the primary cilia formation gene Talpid3 impairs muscle stem cell function

Martinez-Heredia,

Blackwell,

Sebastian

et al. 2023

Commun Biol

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show abstract

“…During embryogenesis, Sonic hedgehog signalling regulates basement membrane components, such as laminin-111 (37–39 . This is crucial for myotome formation and basement membranes are disrupted in the TA 3 mutant 10 .…”

Section: Discussionmentioning

confidence: 99%

Muscle stem cell function is impaired in absence of Talpid3 - a gene required for primary cilia formation

Martinez-Heredia

Blackwell

Sebastian

et al. 2022

Preprint

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Skeletal muscle stem cells (MuSC) are crucial for tissue homeostasis and repair after injury. Following activation, they proliferate to generate differentiating myoblasts. A proportion of cells self-renew, re-enter the MuSC niche under the basal lamina outside the myofiber and become quiescent. Quiescent MuSC have a primary cilium, which is disassembled upon cell cycle entry. Ex vivo experiments suggest cilia are important for MuSC self-renewal, however, their role in muscle regeneration in vivo remains poorly understood. Talpid3 (TA3) is essential for primary cilia formation and Hedgehog (Hh) signalling. Here we use tamoxifen-inducible conditional deletion of TA3 in MuSC (iSC-KO) and show that regeneration is impaired in response to cytotoxic injury. Repeat injury exacerbates the regeneration phenotype in TA3iSC-KO mice, indicating depletion of MuSCs. Single cell transcriptomics of MuSC progeny isolated from myofibers identifies components of several signalling pathways, which are deregulated in absence of TA3, including Hh and Wnt. Pharmacological activation of Wnt restores muscle regeneration, while purmorphamine, an activator of the Smoothened (Smo) co-receptor in the Hh pathway, has no effect. Together, our data suggest that TA3 and primary cilia are important for MuSC self-renewal, and that pharmacological treatment can efficiently restore muscle regeneration.

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“…The first ECM proteins identified in the mammalian preimplantation embryo are the laminins subunits α1, α5, β1, and γ1 (Miner et al, 2004). While laminin β1 and γ1 subunits are nearly ubiquitous and shared by many laminin isoforms, laminin α subunits have more specific spatiotemporal distribution patterns (Pickering et al, 2017). Laminins generate honeycomb-like networks connected in a spot-welding-like manner by adhesive aggregates containing perlecan (Behrens et al, 2012).…”

Section: Compositionmentioning

confidence: 99%

Basement Membranes in Development and Disease

Sekiguchi

Yamada

2018

Current Topics in Developmental Biology

171

146

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The basement membrane is a thin but dense, sheet-like specialized type of extracellular matrix that has remarkably diverse functions tailored to individual tissues and organs. Tightly controlled spatial and temporal changes in its composition and structure contribute to the diversity of basement membrane functions. These different basement membranes undergo dynamic transformations throughout animal life, most notably during development. Numerous developmental mechanisms are regulated or mediated by basement membranes, often by a combination of molecular and mechanical processes. A particularly important process involves cell transmigration through a basement membrane because of its link to cell invasion in disease. While developmental and disease processes share some similarities, what clearly distinguishes the two is dysregulation of cells and extracellular matrices in disease. With its relevance to many developmental and disease processes, the basement membrane is a vitally important area of research that may provide novel insights into biological mechanisms and development of innovative therapeutic approaches. Here we present a review of developmental and disease dynamics of basement membranes in Caenorhabditis elegans, Drosophila, and vertebrates.

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Hedgehog signalling acts upstream of Laminin alpha1 transcription in the zebrafish paraxial mesoderm

Cited by 11 publications

References 72 publications

Absence of the primary cilia formation gene Talpid3 impairs muscle stem cell function

Absence of the primary cilia formation gene Talpid3 impairs muscle stem cell function

Muscle stem cell function is impaired in absence of Talpid3 - a gene required for primary cilia formation

Basement Membranes in Development and Disease

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