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Article ; Online: Dishevelled controls bulk cadherin dynamics and the stability of individual cadherin clusters during convergent extension.

Huebner, Robert J / Wallingford, John B

2022 Volume 33, Issue 14, Page(s) br26

Abstract: Animals are shaped through the movement of large cellular collectives. Such morphogenetic processes require cadherin-based cell adhesion to maintain tissue cohesion and planar cell polarity to coordinate movement. Despite a vast literature surrounding ... ...

Abstract	Animals are shaped through the movement of large cellular collectives. Such morphogenetic processes require cadherin-based cell adhesion to maintain tissue cohesion and planar cell polarity to coordinate movement. Despite a vast literature surrounding cadherin-based adhesion and planar cell polarity, it is unclear how these molecular networks interface. Here we investigate the relationship between cadherins and planar cell polarity during gastrulation cell movements in
MeSH term(s)	Animals ; Cadherins/metabolism ; Morphogenesis ; Gastrulation/physiology ; Xenopus laevis/metabolism ; Cell Adhesion/physiology
Chemical Substances	Cadherins
Language	English
Publishing date	2022-10-12
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	1098979-1
ISSN	1939-4586 ; 1059-1524
ISSN (online)	1939-4586
ISSN	1059-1524
DOI	10.1091/mbc.E22-06-0194
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Zs.A 2853: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
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Article ; Online: Collective cell migration is spatiotemporally regulated during mammary epithelial bifurcation.

Neumann, Neil M / Kim, Daniel M / Huebner, Robert J / Ewald, Andrew J

Journal of cell science

2023 Volume 136, Issue 1

Abstract: Branched epithelial networks are generated through an iterative process of elongation and bifurcation. We sought to understand bifurcation of the mammary epithelium. To visualize this process, we utilized three-dimensional (3D) organotypic culture and ... ...

Abstract	Branched epithelial networks are generated through an iterative process of elongation and bifurcation. We sought to understand bifurcation of the mammary epithelium. To visualize this process, we utilized three-dimensional (3D) organotypic culture and time-lapse confocal microscopy. We tracked cell migration during bifurcation and observed local reductions in cell speed at the nascent bifurcation cleft. This effect was proximity dependent, as individual cells approaching the cleft reduced speed, whereas cells exiting the cleft increased speed. As the cells slow down, they orient both migration and protrusions towards the nascent cleft, while cells in the adjacent branches orient towards the elongating tips. We next tested the hypothesis that TGF-β signaling controls mammary branching by regulating cell migration. We first validated that addition of TGF-β1 (TGFB1) protein increased cleft number, whereas inhibition of TGF-β signaling reduced cleft number. Then, consistent with our hypothesis, we observed that pharmacological inhibition of TGF-β1 signaling acutely decreased epithelial migration speed. Our data suggest a model for mammary epithelial bifurcation in which TGF-β signaling regulates cell migration to determine the local sites of bifurcation and the global pattern of the tubular network.
MeSH term(s)	Animals ; Transforming Growth Factor beta1/pharmacology ; Transforming Growth Factor beta1/metabolism ; Morphogenesis ; Mammary Glands, Animal ; Epithelium/metabolism ; Cell Movement ; Epithelial Cells/metabolism
Chemical Substances	Transforming Growth Factor beta1
Language	English
Publishing date	2023-01-05
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	2993-2
ISSN	1477-9137 ; 0021-9533
ISSN (online)	1477-9137
ISSN	0021-9533
DOI	10.1242/jcs.259275
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Zs.A 1200: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
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Article ; Online: Convergent extension requires adhesion-dependent biomechanical integration of cell crawling and junction contraction.

Weng, Shinuo / Huebner, Robert J / Wallingford, John B

Cell reports

2022 Volume 39, Issue 4, Page(s) 110666

Abstract: Convergent extension (CE) is an evolutionarily conserved collective cell movement that elongates several organ systems during development. Studies have revealed two distinct cellular mechanisms, one based on cell crawling and the other on junction ... ...

Abstract	Convergent extension (CE) is an evolutionarily conserved collective cell movement that elongates several organ systems during development. Studies have revealed two distinct cellular mechanisms, one based on cell crawling and the other on junction contraction. Whether these two behaviors collaborate is unclear. Here, using live-cell imaging, we show that crawling and contraction act both independently and jointly but that CE is more effective when they are integrated via mechano-reciprocity. We thus developed a computational model considering both crawling and contraction. This model recapitulates the biomechanical efficacy of integrating the two modes and further clarifies how the two modes and their integration are influenced by cell adhesion. Finally, we use these insights to understand the function of an understudied catenin, Arvcf, during CE. These data are significant for providing interesting biomechanical and cell biological insights into a fundamental morphogenetic process that is implicated in human neural tube defects and skeletal dysplasias.
MeSH term(s)	Cell Adhesion ; Cell Adhesion Molecules/metabolism ; Cell Movement ; Humans ; Morphogenesis ; Neural Tube Defects
Chemical Substances	Cell Adhesion Molecules
Language	English
Publishing date	2022-04-27
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2649101-1
ISSN	2211-1247 ; 2211-1247
ISSN (online)	2211-1247
ISSN	2211-1247
DOI	10.1016/j.celrep.2022.110666
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Article ; Online: Coming to Consensus: A Unifying Model Emerges for Convergent Extension.

Huebner, Robert J / Wallingford, John B

Developmental cell

2019 Volume 48, Issue 1, Page(s) 126

Language	English
Publishing date	2019-02-01
Publishing country	United States
Document type	Journal Article ; Published Erratum
ZDB-ID	2054967-2
ISSN	1878-1551 ; 1534-5807
ISSN (online)	1878-1551
ISSN	1534-5807
DOI	10.1016/j.devcel.2018.12.006
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Zs.A 5742: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
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Article ; Online: Coming to Consensus: A Unifying Model Emerges for Convergent Extension.

Huebner, Robert J / Wallingford, John B

Developmental cell

2018 Volume 46, Issue 4, Page(s) 389–396

Abstract: Cell motility is a widespread biological property that is best understood in the context of individual cell migration. Indeed, studies of migration in culture have provided tremendous insight into the signals and mechanics involved and have laid the ... ...

Abstract	Cell motility is a widespread biological property that is best understood in the context of individual cell migration. Indeed, studies of migration in culture have provided tremendous insight into the signals and mechanics involved and have laid the foundation for our understanding of similar migrations by larger cellular collectives. By contrast, our understanding of another flavor of movement, cell intercalation during convergent extension, is only now emerging. Here, we integrate divergent findings related to intercalation in different settings into a unifying model, paying attention to how this model does and does not resemble current models for directed cell migration.
MeSH term(s)	Animals ; Body Patterning/physiology ; Cell Culture Techniques ; Cell Movement/physiology ; Consensus ; Humans ; Models, Biological ; Morphogenesis/physiology
Language	English
Publishing date	2018-08-21
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Review
ZDB-ID	2054967-2
ISSN	1878-1551 ; 1534-5807
ISSN (online)	1878-1551
ISSN	1534-5807
DOI	10.1016/j.devcel.2018.08.003
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Zs.A 5742: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
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Article ; Online: ARVCF catenin controls force production during vertebrate convergent extension.

Huebner, Robert J / Weng, Shinuo / Lee, Chanjae / Sarıkaya, Sena / Papoulas, Ophelia / Cox, Rachael M / Marcotte, Edward M / Wallingford, John B

Developmental cell

2022 Volume 57, Issue 9, Page(s) 1119–1131.e5

Abstract: The design of an animal's body plan is encoded in the genome, and the execution of this program is a mechanical progression involving coordinated movement of proteins, cells, and whole tissues. Thus, a challenge to understanding morphogenesis is ... ...

Abstract	The design of an animal's body plan is encoded in the genome, and the execution of this program is a mechanical progression involving coordinated movement of proteins, cells, and whole tissues. Thus, a challenge to understanding morphogenesis is connecting events that occur across various length scales. Here, we describe how a poorly characterized adhesion effector, Arvcf catenin, controls Xenopus head-to-tail axis extension. We find that Arvcf is required for axis extension within the intact organism but not within isolated tissues. We show that the organism-scale phenotype results from a defect in tissue-scale force production. Finally, we determine that the force defect results from the dampening of the pulsatile recruitment of cell adhesion and cytoskeletal proteins to membranes. These results provide a comprehensive understanding of Arvcf function during axis extension and produce an insight into how a cellular-scale defect in adhesion results in an organism-scale failure of development.
MeSH term(s)	Animals ; Armadillo Domain Proteins/genetics ; Armadillo Domain Proteins/metabolism ; Cadherins/metabolism ; Catenins ; Cell Adhesion Molecules/metabolism ; Morphogenesis ; Phosphoproteins/metabolism ; Xenopus laevis/metabolism
Chemical Substances	Armadillo Domain Proteins ; Cadherins ; Catenins ; Cell Adhesion Molecules ; Phosphoproteins
Language	English
Publishing date	2022-04-26
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2054967-2
ISSN	1878-1551 ; 1534-5807
ISSN (online)	1878-1551
ISSN	1534-5807
DOI	10.1016/j.devcel.2022.04.001
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Zs.A 5742: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
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Article ; Online: Cellular foundations of mammary tubulogenesis.

Huebner, Robert J / Ewald, Andrew J

Seminars in cell & developmental biology

2014 Volume 31, Page(s) 124–131

Abstract: The mammary gland is composed of a highly branched network of epithelial tubes, embedded within a complex stroma. The mammary epithelium originates during embryonic development from an epidermal placode. However, the majority of ductal elongation and ... ...

Abstract	The mammary gland is composed of a highly branched network of epithelial tubes, embedded within a complex stroma. The mammary epithelium originates during embryonic development from an epidermal placode. However, the majority of ductal elongation and bifurcation occurs postnatally, in response to steroid hormone and growth factor receptor signaling. The process of pubertal branching morphogenesis involves both elongation of the primary ducts across the length of the fat pad and a wave of secondary branching that elaborates the ductal network. Recent studies have revealed that mammary epithelial morphogenesis is accomplished by transitions between simple and stratified organization. During active morphogenesis, the epithelium is stratified, highly proliferative, has few intercellular junctions, and exhibits incomplete apico-basal polarity. In this review, we discuss recent advances in our understanding of the relationship between epithelial architecture, epithelial polarity, and ductal elongation.
MeSH term(s)	Animals ; Epithelium/growth & development ; Female ; Humans ; Mammary Glands, Animal/cytology ; Mammary Glands, Animal/growth & development ; Mammary Glands, Human/cytology ; Mammary Glands, Human/growth & development ; Morphogenesis
Language	English
Publishing date	2014-04-18
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	1312473-0
ISSN	1096-3634 ; 1084-9521
ISSN (online)	1096-3634
ISSN	1084-9521
DOI	10.1016/j.semcdb.2014.04.019
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Article ; Online: Mechanical heterogeneity along single cell-cell junctions is driven by lateral clustering of cadherins during vertebrate axis elongation.

Huebner, Robert J / Malmi-Kakkada, Abdul Naseer / Sarıkaya, Sena / Weng, Shinuo / Thirumalai, D / Wallingford, John B

eLife

2021 Volume 10

Abstract: Morphogenesis is governed by the interplay of molecular signals and mechanical forces across multiple length scales. The last decade has seen tremendous advances in our understanding of the dynamics of protein localization and turnover at subcellular ... ...

Abstract	Morphogenesis is governed by the interplay of molecular signals and mechanical forces across multiple length scales. The last decade has seen tremendous advances in our understanding of the dynamics of protein localization and turnover at subcellular length scales, and at the other end of the spectrum, of mechanics at tissue-level length scales. Integrating the two remains a challenge, however, because we lack a detailed understanding of the subcellular patterns of mechanical properties of cells within tissues. Here, in the context of the elongating body axis of
MeSH term(s)	Animals ; Body Patterning ; Cadherins/metabolism ; Cell Polarity ; Intercellular Junctions/metabolism ; Morphogenesis ; Single-Cell Analysis ; Xenopus/embryology
Chemical Substances	Cadherins
Language	English
Publishing date	2021-05-25
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	2687154-3
ISSN	2050-084X ; 2050-084X
ISSN (online)	2050-084X
ISSN	2050-084X
DOI	10.7554/eLife.65390
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Article ; Online: A temporally resolved transcriptome for developing "Keller" explants of the Xenopus laevis dorsal marginal zone.

Kakebeen, Anneke D / Huebner, Robert J / Shindo, Asako / Kwon, Kujin / Kwon, Taejoon / Wills, Andrea E / Wallingford, John B

Developmental dynamics : an official publication of the American Association of Anatomists

2021 Volume 250, Issue 5, Page(s) 717–731

Abstract: Background: Explanted tissues from vertebrate embryos reliably develop in culture and have provided essential paradigms for understanding embryogenesis, from early embryological investigations of induction, to the extensive study of Xenopus animal caps, ...

Abstract	Background: Explanted tissues from vertebrate embryos reliably develop in culture and have provided essential paradigms for understanding embryogenesis, from early embryological investigations of induction, to the extensive study of Xenopus animal caps, to the current studies of mammalian gastruloids. Cultured explants of the Xenopus dorsal marginal zone ("Keller" explants) serve as a central paradigm for studies of convergent extension cell movements, yet we know little about the global patterns of gene expression in these explants. Results: In an effort to more thoroughly develop this important model system, we provide here a time-resolved bulk transcriptome for developing Keller explants. Conclusions: The dataset reported here provides a useful resource for those using Keller explants for studies of morphogenesis and provide genome-scale insights into the temporal patterns of gene expression in an important tissue when explanted and grown in culture.
MeSH term(s)	Animals ; Embryo Culture Techniques ; Gastrula/metabolism ; Transcriptome ; Xenopus laevis/genetics ; Xenopus laevis/metabolism
Language	English
Publishing date	2021-01-28
Publishing country	United States
Document type	Evaluation Study ; Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	1102541-4
ISSN	1097-0177 ; 1058-8388
ISSN (online)	1097-0177
ISSN	1058-8388
DOI	10.1002/dvdy.289
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Article ; Online: Mammary epithelial tubes elongate through MAPK-dependent coordination of cell migration.

Huebner, Robert J / Neumann, Neil M / Ewald, Andrew J

Development (Cambridge, England)

2016 Volume 143, Issue 6, Page(s) 983–993

Abstract: Mammary branching morphogenesis is regulated by receptor tyrosine kinases (RTKs). We sought to determine how these RTK signals alter proliferation and migration to accomplish tube elongation in mouse. Both behaviors occur but it has been difficult to ... ...

Abstract	Mammary branching morphogenesis is regulated by receptor tyrosine kinases (RTKs). We sought to determine how these RTK signals alter proliferation and migration to accomplish tube elongation in mouse. Both behaviors occur but it has been difficult to determine their relative contribution to elongation in vivo, as mammary adipocytes scatter light and limit the depth of optical imaging. Accordingly, we utilized 3D culture to study elongation in an experimentally accessible setting. We first used antibodies to localize RTK signals and discovered that phosphorylated ERK1/2 (pERK) was spatially enriched in cells near the front of elongating ducts, whereas phosphorylated AKT was ubiquitous. We next observed a gradient of cell migration speeds from rear to front of elongating ducts, with the front characterized by both high pERK and the fastest cells. Furthermore, cells within elongating ducts oriented both their protrusions and their migration in the direction of tube elongation. By contrast, cells within the organoid body were isotropically protrusive. We next tested the requirement for proliferation and migration. Early inhibition of proliferation blocked the creation of migratory cells, whereas late inhibition of proliferation did not block continued duct elongation. By contrast, pharmacological inhibition of either MEK or Rac1 signaling acutely blocked both cell migration and duct elongation. Finally, conditional induction of MEK activity was sufficient to induce collective cell migration and ductal elongation. Our data suggest a model for ductal elongation in which RTK-dependent proliferation creates motile cells with high pERK, the collective migration of which acutely requires both MEK and Rac1 signaling.
MeSH term(s)	Animals ; Anisotropy ; Cell Movement ; Cell Proliferation ; Epithelial Cells/cytology ; Extracellular Signal-Regulated MAP Kinases/metabolism ; Female ; Humans ; Mammary Glands, Animal/cytology ; Mice, Transgenic ; Mitogen-Activated Protein Kinase Kinases/metabolism ; Morphogenesis ; Organoids/metabolism ; Phosphorylation ; Signal Transduction ; rac1 GTP-Binding Protein/metabolism
Chemical Substances	Extracellular Signal-Regulated MAP Kinases (EC 2.7.11.24) ; Mitogen-Activated Protein Kinase Kinases (EC 2.7.12.2) ; rac1 GTP-Binding Protein (EC 3.6.5.2)
Language	English
Publishing date	2016-03-15
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	90607-4
ISSN	1477-9129 ; 0950-1991
ISSN (online)	1477-9129
ISSN	0950-1991
DOI	10.1242/dev.127944
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