Cell influx and contractile actomyosin force drive mammary bud growth and invagination

Trela, Ewelina; Lan, Qiang; Myllymäki, Satu-Marja; Villeneuve, Clémentine; Lindström, Riitta; Kumar, Vinod; Wickström, Sara A.; Mikkola, Marja L.

doi:10.1083/jcb.202008062

Cited by 14 publications

(15 citation statements)

References 62 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…As pulling the fiber away from a cell will form an outward membrane deformation, this may trigger activation of the self-organizing circuit and LE extension in that direction. Hence, it is plausible to envision that pulling on the same fiber may yield self-organization of cells into equidistant cell aggregates, which has been observed in vitro ( Trappmann et al, 2017 ) and in vivo ( Biggs et al, 2018 ; Trela et al, 2021 ). To determine this putative emerging property, the activation status of Integrins in neighboring cells could be imaged, and corresponding motion pattern determined.…”

Section: Mechanochemical Feedback Loop In 2d and 3d—a Case Studymentioning

confidence: 99%

Moving through a changing world: Single cell migration in 2D vs. 3D

Pawluchin

Galic

2022

Front. Cell Dev. Biol.

View full text Add to dashboard Cite

Migration of single adherent cells is frequently observed in the developing and adult organism and has been the subject of many studies. Yet, while elegant work has elucidated molecular and mechanical cues affecting motion dynamics on a flat surface, it remains less clear how cells migrate in a 3D setting. In this review, we explore the changing parameters encountered by cells navigating through a 3D microenvironment compared to cells crawling on top of a 2D surface, and how these differences alter subcellular structures required for propulsion. We further discuss how such changes at the micro-scale impact motion pattern at the macro-scale.

show abstract

Section: Mechanochemical Feedback Loop In 2d and 3d—a Case Studymentioning

confidence: 99%

Moving through a changing world: Single cell migration in 2D vs. 3D

Pawluchin

Galic

2022

Front. Cell Dev. Biol.

View full text Add to dashboard Cite

show abstract

“…All measurements were done in three dimensions from whole-mount volume renderings of confocal optical Z-stacks. For quantifying cell density and proliferation, individual cell borders were visualized and traced in 3D with fluorescent reporters in whole-mount tissues; measurements were done as described previously (Mogollón et al, 2021; Trela et al, 2021). Differences between groups of: bud dimensions, cell number, cell density, and caspase-3 presence were assessed with the Mann-Whitney U test.…”

Section: Methodsmentioning

confidence: 99%

“…Tooth development begins with the initiation stage, which comprises a thickening of the epithelium (placode), followed by the bud stage with a condensation of the mesenchyme and epithelial invagination (Pispa and Thesleff, 2003, Jernvall and Thesleff, 2000). These morphogenetic events are controlled by well-known conserved pathways that are used reiteratively, but how these actions translate to different cellular behaviors is only beginning to be understood (Ahtiainen et al, 2014, Kuony and Michon, 2017, Biggs et al, 2018, Mogollón et al, 2021, Trela et al, 2021). Specialized relatively small groups of cells called signaling centers play an essential role regulating cell behaviors, doing so by secreting factors such as sonic hedgehog (Shh), and molecules belonging to the Wnt, Fgf, and Bmp families.…”

Section: Introductionmentioning

confidence: 99%

Foxi3 Suppresses Signaling Center Fate and is Necessary for the Early Development of Mouse Teeth

Mogollón

Kangasniemi

Moustakas-Verho

et al. 2022

Preprint

View full text Add to dashboard Cite

Tooth morphogenesis is regulated by ectodermal-mesenchymal interactions which are controlled by reiteratively used, evolutionarily conserved pathways. How these signals translate into different cellular behaviors is beginning to be understood. Embryonic cell behaviors are regulated by signaling centers that define organ position, size, and shape. The recently identified initiation knots (IKs) and the well-known enamel knots (EK) are tooth epithelial signaling centers that drive proliferation of the neighboring cells and are involved at different stages of morphogenesis, from the early epithelial thickening to the final formation of shape. Signaling center cell fate and maintenance can be regulated by numerous factors. Here, we studied the early stages of murine incisor and molar epithelial morphogenesis and overcame the previous shortage of early-stage mutant models to functionally manipulate the initiation processes of tooth morphogenesis. We achieved the early conditional knock down of the forkhead-box transcription factor Foxi3 during tooth initiation and used imaging approaches to explore cellular and molecular disease mechanisms, specifically those related to signaling center dysfunction in tooth dysplasia. We show that early deficiency of Foxi3 in incisors and molars frequently arrests growth at bud stage, whereas later knockdown of Foxi3 affects tooth downgrowth and shape. Cell-level analyses revealed a decrease in epithelial proliferation and the ectopic appearance of cells with hallmarks of signaling centers: quiescent cell state and canonical Wnt activity. However, the distribution of these cells was wider all over the tooth buds with abnormal decrease of apoptosis. We postulate that, depending on Foxi3 expression levels, the bud cells shift commitment into signaling center fate, ultimately leading to growth arrest or growth/shape changes, implicating Foxi3 as a regulator of cell fates between the signaling centers and proliferating bud cells.

show abstract

“…The copyright holder for this preprint this version posted April 24, 2023. ; https://doi.org/10.1101/2023.04. 24.538064 doi: bioRxiv preprint that they might be functionally connected 8,10 . However, whether a causal link exists between these phenomena is currently unknown.…”

Section: Introductionmentioning

confidence: 99%

“…The copyright holder for this preprint this version posted April 24, 2023. ; https://doi.org/10.1101/2023.04. 24.538064 doi: bioRxiv preprint…”

Section: Introductionmentioning

confidence: 99%

On growth and form of the mammary gland: Mesenchyme instructs growth while epithelium directs branching

Lan

Trela

Lindström

et al. 2023

Preprint

Self Cite

View full text Add to dashboard Cite

Mammary gland is a unique organ that undergoes dynamic alterations throughout a female's reproductive life, making it an ideal model for developmental, stem cell and cancer biology research. Mammary gland development begins in utero and proceeds via a quiescent bud stage before the initial outgrowth and subsequent branching morphogenesis. How mammary epithelial cells transit from quiescence to an actively proliferating and branching tissue during embryogenesis and, importantly, how the branch pattern is determined remain largely unknown. Here we provide evidence indicating that epithelial cell proliferation, segregation into basal and luminal lineages that characterize the postnatal mammary duct, and onset of branching are independent processes, yet partially coordinated by the Eda signaling pathway. By performing heterotypic and -chronic epithelial-mesenchymal recombination experiments between mammary and salivary gland tissues and ex vivo live imaging, we demonstrate that unlike previously concluded, the mode of branching is an intrinsic property of the mammary epithelium while the growth pace and density of the mammary ductal tree are dramatically affected by the origin of the mesenchyme. Transcriptomic profiling of mammary and salivary gland mesenchymes and ex vivo and in vivo functional studies disclose that mesenchymal Wnt/beta-catenin signaling, and in particular IGF-1 downstream of it critically regulate mammary gland growth.

show abstract

Cell influx and contractile actomyosin force drive mammary bud growth and invagination

Cited by 14 publications

References 62 publications

Moving through a changing world: Single cell migration in 2D vs. 3D

Moving through a changing world: Single cell migration in 2D vs. 3D

Foxi3 Suppresses Signaling Center Fate and is Necessary for the Early Development of Mouse Teeth

On growth and form of the mammary gland: Mesenchyme instructs growth while epithelium directs branching

Contact Info

Product

Resources

About