Mmp17b Is Essential for Proper Neural Crest Cell Migration In Vivo

Leigh, Noah R.; Schupp, Marcus-Oliver; Li, Keguo; Vakeel, Padmanabhan; Gastonguay, Adam; Wang, Ling; Chun, Chang Zoon; Wilkinson, George A.; Ramchandran, Ramani

doi:10.1371/journal.pone.0076484

Cited by 44 publications

(67 citation statements)

References 37 publications

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“…Another Drosophila MMP, Mmp1, promotes wound healing by permitting cell migration via ECM repair (Stevens and Page-McCaw, 2012), suggesting that Mmp2 similarly may act as a positive regulator of cell migration. In vertebrate embryos, MMPs (MMP-2 and Mmp17b) are important for neural crest cell migration (Duong and Erickson, 2004; Leigh et al, 2013). vkg (collagen IV) is known to be secreted from HCs which in turn promotes renal tubule morphogenesis in Drosophila embryos (Bunt et al, 2010).…”

Section: Resultsmentioning

confidence: 99%

Comparative analysis of gene expression profiles for several migrating cell types identifies cell migration regulators

Bae

Macabenta

Curtis

et al. 2017

Mechanisms of Development

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Cell migration is an instrumental process that ensures cells are properly positioned to support the specification of distinct tissue types during development. To provide insight, we used fluorescence activated cell sorting (FACS) to isolate two migrating cell types from the Drosophila embryo: caudal visceral mesoderm (CVM) cells, precursors of longitudinal muscles of the gut, and hemocytes (HCs), the Drosophila equivalent of blood cells. ~350 genes were identified from each of the sorted samples using RNA-seq, and in situ hybridization was used to confirm expression within each cell type or, alternatively, within other interacting, co-sorted cell types. To start, the two gene expression profiling datasets were compared to identify cell migration regulators that are potentially generally-acting. 73 genes were present in both CVM cell and HC gene expression profiles, including the transcription factor Zinc finger homeodomain-1 (Zfh1). Comparisons with gene expression profiles of Drosophila border cells that migrate during oogenesis had a more limited overlap, with only the genes neyo (neo) and singed (sn) found to be expressed in border cells as well as CVM cells and HCs, respectively. neo encodes a protein with Zona pellucida domain linked to cell polarity, while sn encodes an actin binding protein. Tissue specific RNAi expression coupled with live in vivo imaging was used to confirm cell-autonomous roles for Zfh1 and Neo in supporting CVM cell migration, whereas previous studies had demonstrated a role for Sn in supporting HC migration. In addition, comparisons were made to migrating cells from vertebrates. Seven genes were found expressed by chick neural crest cells, CVM cells, and HCs including extracellular matrix (ECM) proteins and proteases. In summary, we show that genes shared in common between CVM cells, HCs, and other migrating cell types can help identify regulators of cell migration. Our analyses show that Neo in addition to Zfh1 and Sn studied previously impact cell migration. This study also suggests that modification of the extracellular milieu may be a fundamental requirement for cells that undergo cell streaming migratory behaviors.

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Section: Resultsmentioning

confidence: 99%

Comparative analysis of gene expression profiles for several migrating cell types identifies cell migration regulators

Bae

Macabenta

Curtis

et al. 2017

Mechanisms of Development

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“…13,14,35 MMP17 overexpression in tumor cells affects the covering of vascular endothelial cells by pericytes, perivascular cells related to VSMC, 36 and the zebrafish homolog Mmp17b is required for migration of neural crest cells, which contributes to VSMCs in certain aortic regions. 37 Despite these findings and the reported expression of several MMPs during mouse aorta development, 16 no other MMP mutations or MMP-deficient mouse models have been shown to produce aortic aneurysm.…”

Section: Discussionmentioning

confidence: 99%

Deficiency of MMP17/MT4-MMP Proteolytic Activity Predisposes to Aortic Aneurysm in Mice

Martín-Alonso

García-Redondo

Guo

et al. 2015

Circulation Research

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A ortic aneurysm predisposes the aorta to dissection or rupture and causes 1% to 2% of deaths in developed countries.1 Thoracic aortic aneurysms and acute aortic dissections (TAADs) that affect young patients result primarily from genetic mutations. 2 The vulnerability of the aortic wall is mainly because of its poor ability to appropriately accommodate hemodynamic changes. The aortic wall, particularly in the thoracic aorta, is able to distend without requiring subsequent contraction of vascular smooth muscle cells (VSMCs) because of the elastic recoil provided by the layers of elastin lamellae.3 These mechanical properties depend on the intimate physical and mechanical connections of differentiated VSMCs with the extracellular matrix (ECM, mostly elastin, and collagen) that they produce and organize, connections that are established through force-dependent adhesion proteins (integrins), and the cytoskeleton (actin and myosin).3 During aortic development, VSMCs differentiate from neural crest and second heart field progenitors and also from mesenchymal progenitors recruited to the nascent endothelial tube; during this process, proper interaction needs to Molecular Medicine© 2015 American Heart Association, Inc. Rationale: Aortic dissection or rupture resulting from aneurysm causes 1% to 2% of deaths in developed countries.These disorders are associated with mutations in genes that affect vascular smooth muscle cell differentiation and contractility or extracellular matrix composition and assembly. However, as many as 75% of patients with a family history of aortic aneurysms do not have an identified genetic syndrome.Objective: To determine the role of the protease MMP17/MT4-MMP in the arterial wall and its possible relevance in human aortic pathology. be established between VSMCs and the ECM. 4 Detailed analysis of pulmonary artery development demonstrated that formation of the vessel wall involves the induction of successive layers of VSMCs and the invasion of the outer layers through the reorientation and radial migration of the inner ones. Methods and Results:5 Transforming growth factor (TGF)-B has been extensively studied as an inducer of VSMC maturation, and more recent studies have identified gradients of platelet-derived growth factor (PDGF)-B and other not-yet identified signals as regulators of VSMC differentiation, providing new insights into artery wall development. 5This intimate connection between VSMCs and the ECM ensures that alterations to one affect the other and can have similar effects on the overall mechanical behavior of the vessel. Thus, TAADs can be caused by mutations that affect VSMC function or that alter ECM composition and assembly.2 For example, Marfan syndrome, a genetic syndrome that predisposes to TAAD, is caused by mutations in the fibrillin-1 (FBN1) gene, which encodes an ECM protein necessary for proper elastin formation, 6 whereas in Loeys-Dietz syndrome, TGFB receptors type 1 and 2 (TGFBR1 and TGFBR2) are mutated, 7 resulting in impeded VSMC differentiation.8 Predispositi...

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“…Pharmacological inhibition of MMP2 and 14 impaired melanophore migration in Xenopus [42], but broad spectrum metalloproteinase inhibitors did not affect neural crest migration in several other experiments [43]. Paradoxically, morpholino knockdown of Mmp17b alone significantly impairs neural crest migration in zebrafish [34] and knockdown of Mmp25a disrupts development of neural crest-derived neuromasts [44]. Furthermore, here we show that migration and/or survival of the neural-crest-derived cells of the craniofacial cartilages and otic vesicle is profoundly disrupted by PhN (Fig.…”

Section: Discussionmentioning

confidence: 94%

Experimental Dissection of Metalloproteinase Inhibition-Mediated and Toxic Effects of Phenanthroline on Zebrafish Development.

Ellis

Crawford

2016

Preprint

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Metalloproteinases are zinc-dependent endopeptidases that function as primary effectors of tissue remodelling, cell-signalling, and many other roles. Their regulation is ferociously complex, and is exquisitely sensitive to their molecular milieu, making in vivo studies challenging. Phenanthroline (PhN) is an inexpensive, broad-spectrum inhibitor of metalloproteinases that functions by chelating the catalytic zinc ion, however its use in vivo has been limited due to suspected off-target effects. PhN is very similar in structure to phenanthrene (Phe), a well-studied poly aromatic hydrocarbon (PAH) known to cause toxicity in aquatic animals by activating the aryl hydrocarbon receptor (AhR). We show that zebrafish are more sensitive to PhN than Phe, and that PhN causes a superset of the effects caused by Phe. Morpholino knock-down of the AhR rescues the effects of PhN that are shared with Phe, suggesting these are due to PAH toxicity. The effects of PhN that are not shared with Phe (specifically disruption of neural crest development and angiogenesis) involve processes known to depend on metalloproteinase activity. Furthermore these PhN-specific effects are not rescued by AhR knock-down, suggesting that these are bona fide effects of metalloproteinase inhibition, and that PhN can be used as a broad spectrum metalloproteinase inhibitor for studies with zebrafish in vivo.

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Mmp17b Is Essential for Proper Neural Crest Cell Migration In Vivo

Cited by 44 publications

References 37 publications

Comparative analysis of gene expression profiles for several migrating cell types identifies cell migration regulators

Comparative analysis of gene expression profiles for several migrating cell types identifies cell migration regulators

Deficiency of MMP17/MT4-MMP Proteolytic Activity Predisposes to Aortic Aneurysm in Mice

Experimental Dissection of Metalloproteinase Inhibition-Mediated and Toxic Effects of Phenanthroline on Zebrafish Development.

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