In vivo Neural Crest Cell Migration Is Controlled by “Mixotaxis”

Barriga, Elías H.; Théveneau, Eric

doi:10.3389/fphys.2020.586432

Cited by 29 publications

(28 citation statements)

References 63 publications

(86 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In Wnt1-Tmem2 CKO ;Z/EG embryos, in contrast, vinculin immunoreactivity is greatly diminished in emigrating NCCs and little vinculin localization at the cell periphery is observed in these NCCs (Fig 5E). This is consistent with a recent report that formation of the integrin-vinculin-talin complex is necessary for NCCs emigration [49]. Thus, it is likely that reduced NCCs emigration in Tmem2 CKO mice is caused by the impaired NCC's ability to overcome the barrier effect of HA and form focal adhesion complexes.…”

Section: Tmem2-deficient O9-1 Mouse Neural Crest Cells Are Defective In Migration On Ha-containing Substratessupporting

confidence: 93%

The cell surface hyaluronidase TMEM2 plays an essential role in mouse neural crest cell development and survival

Inubushi

Nakanishi

Abe

et al. 2021

Preprint

View full text Add to dashboard Cite

Neural crest cells (NCCs) are a migratory population that gives rise to a diverse cell lineage, including the craniofacial complex, the peripheral nervous system, and a part of the heart. Hyaluronan (HA) is a major component of the extracellular matrix, and its tissue levels are dynamically regulated in during development. Although the synthesis of HA has been shown to exert substantial influence on embryonic morphogenesis, the functional importance of the catabolic side of HA turnover is poorly understood. Here, we demonstrate that the transmembrane hyaluronidase TMEM2 plays an essential role in NCC development and the morphogenesis of their derivatives. Wnt1-Cre–mediated Tmem2 knockout (Tmem2CKO) mice exhibit severe craniofacial and cardiovascular abnormalities. Analysis of Tmem2 expression using Tmem2 knock-in reporter mice reveals that Tmem2 is expressed at the site of NCC delamination in the neural tube and in Sox9-positive emigrating NCCs, suggesting that Tmem2 is critical for NCC development. Consistent with this possibility, linage tracing analysis reveals that the contribution of Wnt1-Cre–labeled cells to NCC derivatives is significantly reduced in a Tmem2-deficient background. Moreover, the emigration of NCCs from the neural tube is greatly reduced in Tmem2CKO mice. In vitro assays demonstrate that Tmem2 expression is essential for the ability of mouse O9-1 NCCs to form focal adhesion on and migrate into HA-containing substrates. Tmem2CKO mice also exhibit increased apoptotic cell death in NCC-derived tissues. Collectively, our data demonstrate that Tmem2 is essential for normal development of NCC-derivatives, including the craniofacial complex, and that TMEM2-mediated HA degradation allows NCCs to generate a tissue environment suitable for efficient focal adhesion assembly and migration. This study reveals the hitherto unrecognized functional importance of the catabolic side of HA metabolism in embryonic development and highlights the pivotal role of Tmem2 in the process.

show abstract

Section: Tmem2-deficient O9-1 Mouse Neural Crest Cells Are Defective In Migration On Ha-containing Substratessupporting

confidence: 93%

The cell surface hyaluronidase TMEM2 plays an essential role in mouse neural crest cell development and survival

Inubushi

Nakanishi

Abe

et al. 2021

Preprint

View full text Add to dashboard Cite

show abstract

“…These extrinsic cues vary in nature as biochemical, electrical, mechanical cues or even variations in substrate topology have been proposed to direct cell migration (explained below) and extensively discussed in Ref. [1]. Polarity achievement and protrusion formation are key events that allow cells to directionally migrate, and their establishment is activated by cell-intrinsic molecular signalling but oriented by external factors [1] (Fig.…”

Section: Introductionmentioning

confidence: 99%

“…[1]. Polarity achievement and protrusion formation are key events that allow cells to directionally migrate, and their establishment is activated by cell-intrinsic molecular signalling but oriented by external factors [1] (Fig. 1).…”

Section: Introductionmentioning

confidence: 99%

Durotaxis: the mechanical control of directed cell migration

2021

View full text Add to dashboard Cite

Directed cell migration is essential for cells to efficiently migrate in physiological and pathological processes. While migrating in their native environment, cells interact with multiple types of cues, such as mechanical and chemical signals. The role of chemical guidance via chemotaxis has been studied in the past, the understanding of mechanical guidance of cell migration via durotaxis remained unclear until very recently. Nonetheless, durotaxis has become a topic of intensive research and several advances have been made in the study of mechanically guided cell migration across multiple fields. Thus, in this article we provide a state of the art about durotaxis by discussing in silico, in vitro and in vivo data. We also present insights on the general mechanisms by which cells sense, transduce and respond to environmental mechanics, to then contextualize these mechanisms in the process of durotaxis and explain how cells bias their migration in anisotropic substrates. Furthermore, we discuss what is known about durotaxis in vivo and we comment on how haptotaxis could arise from integrating durotaxis and chemotaxis in native environments.

show abstract

“…Directed migration of cells to cues from their environment plays an important role in diverse physiological and pathophysiological processes, including embryo development, inflammation and cancer metastasis (Barriga and Theveneau, 2020;SenGupta et al, 2021). The best understood mode of directed cell migration is chemotaxis, where cells detect a chemical gradient in the environment and migrate relative to that gradient.…”

Section: Introductionmentioning

confidence: 99%

Differential Roles of Actin Crosslinking Proteins Filamin and α-Actinin in Shear Flow-Induced Migration of Dictyostelium discoideum

Cole

Buckler

Marcucci

et al. 2021

Front. Cell Dev. Biol.

View full text Add to dashboard Cite

Shear flow-induced migration is an important physiological phenomenon experienced by multiple cell types, including leukocytes and cancer cells. However, molecular mechanisms by which cells sense and directionally migrate in response to mechanical perturbation are not well understood. Dictyostelium discoideum social amoeba, a well-established model for studying amoeboid-type migration, also exhibits directional motility when exposed to shear flow, and this behavior is preceded by rapid and transient activation of the same signal transduction network that is activated by chemoattractants. The initial response, which can also be observed following brief 2 s stimulation with shear flow, requires an intact actin cytoskeleton; however, what aspect of the cytoskeletal network is responsible for sensing and/or transmitting the signal is unclear. We investigated the role of actin crosslinkers filamin and α-actinin by analyzing initial shear flow-stimulated responses in cells with or without these proteins. Both filamin and α-actinin showed rapid and transient relocalization from the cytosol to the cortex following shear flow stimulation. Using spatiotemporal analysis of Ras GTPase activation as a readout of signal transduction network activity, we demonstrated that lack of α-actinin did not reduce, and, in fact, slightly improved the response to acute mechanical stimulation compared to cells expressing α-actinin. In contrast, shear flow-induced Ras activation was significantly more robust in filamin-null cells rescued with filamin compared to cells expressing empty vector. Reduced responsiveness appeared to be specific to mechanical stimuli and was not due to a change in the basal activity since response to global stimulation with a chemoattractant and random migration was comparable between cells with or without filamin. Finally, while filamin-null cells rescued with filamin efficiently migrated upstream when presented with continuous flow, cells lacking filamin were defective in directional migration. Overall, our study suggests that filamin, but not α-actinin, is involved in sensing and/or transmitting mechanical stimuli that drive directed migration; however, other components of the actin cytoskeleton likely also contribute to the initial response since filamin-null cells were still able to activate the signal transduction network. These findings could have implications for our fundamental understanding of shear flow-induced migration of leukocytes, cancer cells and other amoeboid-type cells.

show abstract

In vivo Neural Crest Cell Migration Is Controlled by “Mixotaxis”

Cited by 29 publications

References 63 publications

The cell surface hyaluronidase TMEM2 plays an essential role in mouse neural crest cell development and survival

The cell surface hyaluronidase TMEM2 plays an essential role in mouse neural crest cell development and survival

Durotaxis: the mechanical control of directed cell migration

Differential Roles of Actin Crosslinking Proteins Filamin and α-Actinin in Shear Flow-Induced Migration of Dictyostelium discoideum

Contact Info

Product

Resources

About