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Article ; Online: Niche-mediated repair of airways is directed in an occupant-dependent manner.

Lyu, Handeng / Warren, Rachel / Gao, Shan / Klinkhammer, Kylie / Yuan, Tingting / Zhang, Jin-San / Brownfield, Douglas / Li, Xiaokun / De Langhe, Stijn P

Cell reports

2022 Volume 41, Issue 12, Page(s) 111863

Abstract: In injured airways of the adult lung, epithelial progenitors are called upon to repair by nearby mesenchymal cells via signals transmitted through the niche. Currently, it is unclear whether repair is coordinated by the mesenchymal cells that maintain ... ...

Abstract	In injured airways of the adult lung, epithelial progenitors are called upon to repair by nearby mesenchymal cells via signals transmitted through the niche. Currently, it is unclear whether repair is coordinated by the mesenchymal cells that maintain the niche or by the airway epithelial cells that occupy it. Here, we show that the spatiotemporal expression of Fgf10 by the niche is primarily orchestrated by the niche's epithelial occupants-both those that reside prior to, and following, injury. During homeostasis, differentiated airway epithelial cells secrete Sonic hedgehog (Shh) to inhibit Fgf10 expression by Gli1
MeSH term(s)	Hedgehog Proteins/metabolism ; Lung/metabolism ; Cell Differentiation ; Epithelial Cells/metabolism ; Mesenchymal Stem Cells/metabolism ; Zinc Finger Protein GLI1/metabolism
Chemical Substances	Hedgehog Proteins ; Zinc Finger Protein GLI1
Language	English
Publishing date	2022-11-19
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.2022.111863
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Alveolar cell fate selection and lifelong maintenance of AT2 cells by FGF signaling.

Brownfield, Douglas G / de Arce, Alex Diaz / Ghelfi, Elisa / Gillich, Astrid / Desai, Tushar J / Krasnow, Mark A

Nature communications

2022 Volume 13, Issue 1, Page(s) 7137

Abstract: The lung's gas exchange surface is comprised of alveolar AT1 and AT2 cells that are corrupted in several common and deadly diseases. They arise from a bipotent progenitor whose differentiation is thought to be dictated by differential mechanical forces. ... ...

Abstract	The lung's gas exchange surface is comprised of alveolar AT1 and AT2 cells that are corrupted in several common and deadly diseases. They arise from a bipotent progenitor whose differentiation is thought to be dictated by differential mechanical forces. Here we show the critical determinant is FGF signaling. Fgfr2 is expressed in the developing progenitors in mouse then restricts to nascent AT2 cells and remains on throughout life. Its ligands are expressed in surrounding mesenchyme and can, in the absence of exogenous mechanical cues, induce progenitors to form alveolospheres with intermingled AT2 and AT1 cells. FGF signaling directly and cell autonomously specifies AT2 fate; progenitors lacking Fgfr2 in vitro and in vivo exclusively acquire AT1 fate. Fgfr2 loss in AT2 cells perinatally results in reprogramming to AT1 identity, whereas loss or inhibition later in life triggers AT2 apoptosis and compensatory regeneration. We propose that Fgfr2 signaling selects AT2 fate during development, induces a cell non-autonomous AT1 differentiation signal, then continuously maintains AT2 identity and survival throughout life.
MeSH term(s)	Animals ; Mice ; Alveolar Epithelial Cells ; Cell Differentiation ; Mesoderm ; Signal Transduction ; Apoptosis
Language	English
Publishing date	2022-11-21
Publishing country	England
Document type	Journal Article
ZDB-ID	2553671-0
ISSN	2041-1723 ; 2041-1723
ISSN (online)	2041-1723
ISSN	2041-1723
DOI	10.1038/s41467-022-34059-1
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Article ; Online: Single-cell Wnt signaling niches maintain stemness of alveolar type 2 cells.

Nabhan, Ahmad N / Brownfield, Douglas G / Harbury, Pehr B / Krasnow, Mark A / Desai, Tushar J

Science (New York, N.Y.)

2018 Volume 359, Issue 6380, Page(s) 1118–1123

Abstract: Alveoli, the lung's respiratory units, are tiny sacs where oxygen enters the bloodstream. They are lined by flat alveolar type 1 (AT1) cells, which mediate gas exchange, and AT2 cells, which secrete surfactant. Rare AT2s also function as alveolar stem ... ...

Abstract	Alveoli, the lung's respiratory units, are tiny sacs where oxygen enters the bloodstream. They are lined by flat alveolar type 1 (AT1) cells, which mediate gas exchange, and AT2 cells, which secrete surfactant. Rare AT2s also function as alveolar stem cells. We show that AT2 lung stem cells display active Wnt signaling, and many of them are near single, Wnt-expressing fibroblasts. Blocking Wnt secretion depletes these stem cells. Daughter cells leaving the Wnt niche transdifferentiate into AT1s: Maintaining Wnt signaling prevents transdifferentiation, whereas abrogating Wnt signaling promotes it. Injury induces AT2 autocrine Wnts, recruiting "bulk" AT2s as progenitors. Thus, individual AT2 stem cells reside in single-cell fibroblast niches providing juxtacrine Wnts that maintain them, whereas injury induces autocrine Wnts that transiently expand the progenitor pool. This simple niche maintains the gas exchange surface and is coopted in cancer.
MeSH term(s)	Animals ; Cell Transdifferentiation ; Fibroblasts/cytology ; Fibroblasts/metabolism ; Lung/physiology ; Lung Neoplasms/metabolism ; Lung Neoplasms/pathology ; Mice ; Mice, Inbred C57BL ; Neoplastic Stem Cells/metabolism ; Neoplastic Stem Cells/pathology ; Pulmonary Alveoli/cytology ; Pulmonary Alveoli/metabolism ; Stem Cell Niche/physiology ; Stem Cells/cytology ; Stem Cells/metabolism ; Wnt Signaling Pathway
Language	English
Publishing date	2018-02-01
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	128410-1
ISSN	1095-9203 ; 0036-8075
ISSN (online)	1095-9203
ISSN	0036-8075
DOI	10.1126/science.aam6603
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Article ; Online: Alveolar progenitor and stem cells in lung development, renewal and cancer.

Desai, Tushar J / Brownfield, Douglas G / Krasnow, Mark A

Nature

2014 Volume 507, Issue 7491, Page(s) 190–194

Abstract: Alveoli are gas-exchange sacs lined by squamous alveolar type (AT) 1 cells and cuboidal, surfactant-secreting AT2 cells. Classical studies suggested that AT1 arise from AT2 cells, but recent studies propose other sources. Here we use molecular markers, ... ...

Abstract	Alveoli are gas-exchange sacs lined by squamous alveolar type (AT) 1 cells and cuboidal, surfactant-secreting AT2 cells. Classical studies suggested that AT1 arise from AT2 cells, but recent studies propose other sources. Here we use molecular markers, lineage tracing and clonal analysis to map alveolar progenitors throughout the mouse lifespan. We show that, during development, AT1 and AT2 cells arise directly from a bipotent progenitor, whereas after birth new AT1 cells derive from rare, self-renewing, long-lived, mature AT2 cells that produce slowly expanding clonal foci of alveolar renewal. This stem-cell function is broadly activated by AT1 injury, and AT2 self-renewal is selectively induced by EGFR (epidermal growth factor receptor) ligands in vitro and oncogenic Kras(G12D) in vivo, efficiently generating multifocal, clonal adenomas. Thus, there is a switch after birth, when AT2 cells function as stem cells that contribute to alveolar renewal, repair and cancer. We propose that local signals regulate AT2 stem-cell activity: a signal transduced by EGFR-KRAS controls self-renewal and is hijacked during oncogenesis, whereas another signal controls reprogramming to AT1 fate.
MeSH term(s)	Animals ; Cell Differentiation ; Cell Division ; Cell Lineage ; Cell Transformation, Neoplastic/metabolism ; Cell Transformation, Neoplastic/pathology ; Cells, Cultured ; Cellular Reprogramming ; Clone Cells/cytology ; ErbB Receptors/metabolism ; Female ; Lung/cytology ; Lung/embryology ; Lung/growth & development ; Lung/pathology ; Lung Neoplasms/metabolism ; Lung Neoplasms/pathology ; Male ; Mice ; Models, Biological ; Multipotent Stem Cells/cytology ; Multipotent Stem Cells/metabolism ; Multipotent Stem Cells/pathology ; Proto-Oncogene Proteins p21(ras)/genetics ; Proto-Oncogene Proteins p21(ras)/metabolism ; Pulmonary Alveoli/cytology ; Regeneration ; Signal Transduction
Chemical Substances	ErbB Receptors (EC 2.7.10.1) ; Hras protein, mouse (EC 3.6.5.2) ; Proto-Oncogene Proteins p21(ras) (EC 3.6.5.2)
Language	English
Publishing date	2014-02-05
Publishing country	England
Document type	Journal Article
ZDB-ID	120714-3
ISSN	1476-4687 ; 0028-0836
ISSN (online)	1476-4687
ISSN	0028-0836
DOI	10.1038/nature12930
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Article: Age-dependent regulation of SARS-CoV-2 cell entry genes and cell death programs correlates with COVID-19 disease severity.

Inde, Zintis / Yapp, Clarence / Joshi, Gaurav N / Spetz, Johan / Fraser, Cameron / Deskin, Brian / Ghelfi, Elisa / Sodhi, Chhinder / Hackam, David J / Kobzik, Lester / Croker, Ben A / Brownfield, Douglas / Jia, Hongpeng / Sarosiek, Kristopher A

bioRxiv : the preprint server for biology

2020

Abstract: Angiotensin-converting enzyme 2 (ACE2) maintains cardiovascular and renal homeostasis but also serves as the entry receptor for the novel severe acute respiratory syndrome coronavirus (SARS-CoV-2), the causal agent of novel coronavirus disease 2019 ( ... ...

Abstract	Angiotensin-converting enzyme 2 (ACE2) maintains cardiovascular and renal homeostasis but also serves as the entry receptor for the novel severe acute respiratory syndrome coronavirus (SARS-CoV-2), the causal agent of novel coronavirus disease 2019 (COVID-19). COVID-19 disease severity is typically lower in pediatric patients than adults (particularly the elderly), but higher rates of hospitalizations requiring intensive care are observed in infants than in older children - the reasons for these differences are unknown. ACE2 is expressed in several adult tissues and cells, including alveolar type 2 cells of the distal lung epithelium, but expression at other ages is largely unexplored. Here we show that ACE2 transcripts are expressed in the lung and trachea shortly after birth, downregulated during childhood, and again expressed at high levels in late adulthood. Notably, the repertoire of cells expressing ACE2 protein in the mouse lung and airways shifts during key phases of lung maturation. In particular, podoplanin-positive cells, which are likely alveolar type I cells responsible for gas exchange, express ACE2 only in advanced age. Similar patterns of expression were evident in analysis of human lung tissue from over 100 donors, along with extreme inter- and intra-individual heterogeneity in ACE2 protein expression in epithelial cells. Furthermore, we find that apoptosis, which is a natural host defense system against viral infection, is dynamically regulated during lung maturation, resulting in periods of heightened apoptotic priming and dependence on pro-survival BCL-2 family proteins including MCL-1. Infection of human lung cells with SARS-CoV-2 triggers an unfolded protein stress response and upregulation of the endogenous MCL-1 inhibitor Noxa; in young individuals, MCL-1 inhibition is sufficient to trigger apoptosis in lung epithelial cells and may thus limit virion production and inflammatory signaling. Overall, we identify strong and distinct correlates of COVID-19 disease severity across lifespan and advance our understanding of the regulation of ACE2 and cell death programs in the mammalian lung. Furthermore, our work provides the framework for translation of apoptosis modulating drugs as novel treatments for COVID-19.
Keywords	covid19
Language	English
Publishing date	2020-09-13
Publishing country	United States
Document type	Preprint
DOI	10.1101/2020.09.13.276923
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Article ; Online: Transient external force induces phenotypic reversion of malignant epithelial structures via nitric oxide signaling.

Ricca, Benjamin L / Venugopalan, Gautham / Furuta, Saori / Tanner, Kandice / Orellana, Walter A / Reber, Clay D / Brownfield, Douglas G / Bissell, Mina J / Fletcher, Daniel A

eLife

2018 Volume 7

Abstract: Non-malignant breast epithelial cells cultured in three-dimensional laminin-rich extracellular matrix (lrECM) form well organized, growth-arrested acini, whereas malignant cells form continuously growing disorganized structures. While the mechanical ... ...

Abstract	Non-malignant breast epithelial cells cultured in three-dimensional laminin-rich extracellular matrix (lrECM) form well organized, growth-arrested acini, whereas malignant cells form continuously growing disorganized structures. While the mechanical properties of the microenvironment have been shown to contribute to formation of tissue-specific architecture, how transient external force influences this behavior remains largely unexplored. Here, we show that brief transient compression applied to single malignant breast cells in lrECM stimulated them to form acinar-like structures, a phenomenon we term 'mechanical reversion.' This is analogous to previously described phenotypic 'reversion' using biochemical inhibitors of oncogenic pathways. Compression stimulated nitric oxide production by malignant cells. Inhibition of nitric oxide production blocked mechanical reversion. Compression also restored coherent rotation in malignant cells, a behavior that is essential for acinus formation. We propose that external forces applied to single malignant cells restore cell-lrECM engagement and signaling lost in malignancy, allowing them to reestablish normal-like tissue architecture.
MeSH term(s)	Acinar Cells/drug effects ; Acinar Cells/metabolism ; Breast/cytology ; Breast/drug effects ; Breast/metabolism ; Breast Neoplasms/metabolism ; Breast Neoplasms/pathology ; Cell Line ; Cell Line, Tumor ; Epithelial Cells/drug effects ; Epithelial Cells/metabolism ; Extracellular Matrix/metabolism ; Humans ; Laminin/metabolism ; Laminin/pharmacology ; Microscopy, Confocal ; Nitric Oxide/metabolism ; Signal Transduction/drug effects ; Stress, Mechanical ; Time-Lapse Imaging/methods
Chemical Substances	Laminin ; Nitric Oxide (31C4KY9ESH)
Language	English
Publishing date	2018-03-21
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; 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.26161
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Article ; Online: Age-dependent regulation of SARS-CoV-2 cell entry genes and cell death programs correlates with COVID-19 disease severity

Inde, Zintis / Yapp, Clarence / Joshi, Gaurav N / Spetz, Johan / Fraser, Cameron / Deskin, Brian / Ghelfi, Elisa / Sodhi, Chhinder / Hackam, David / Kobzik, Lester / Croker, Ben / Brownfield, Douglas / Jia, Hongpeng / Sarosiek, Kristopher A.

bioRxiv

Abstract	Angiotensin-converting enzyme 2 (ACE2) maintains cardiovascular and renal homeostasis but also serves as the entry receptor for the novel severe acute respiratory syndrome coronavirus (SARS-CoV-2), the causal agent of novel coronavirus disease 2019 (COVID-19). COVID-19 disease severity is typically lower in pediatric patients than adults (particularly the elderly), but higher rates of hospitalizations requiring intensive care are observed in infants than in older children - the reasons for these differences are unknown. ACE2 is expressed in several adult tissues and cells, including alveolar type 2 cells of the distal lung epithelium, but expression at other ages is largely unexplored. Here we show that ACE2 transcripts are expressed in the lung and trachea shortly after birth, downregulated during childhood, and again expressed at high levels in late adulthood. Notably, the repertoire of cells expressing ACE2 protein in the mouse lung and airways shifts during key phases of lung maturation. In particular, podoplanin-positive cells, which are likely alveolar type I cells responsible for gas exchange, express ACE2 only in advanced age. Similar patterns of expression were evident in analysis of human lung tissue from over 100 donors, along with extreme inter- and intra-individual heterogeneity in ACE2 protein expression in epithelial cells. Furthermore, we find that apoptosis, which is a natural host defense system against viral infection, is dynamically regulated during lung maturation, resulting in periods of heightened apoptotic priming and dependence on pro-survival BCL-2 family proteins including MCL-1. Infection of human lung cells with SARS-CoV-2 triggers an unfolded protein stress response and upregulation of the endogenous MCL-1 inhibitor Noxa; in young individuals, MCL-1 inhibition is sufficient to trigger apoptosis in lung epithelial cells and may thus limit virion production and inflammatory signaling. Overall, we identify strong and distinct correlates of COVID-19 disease severity across lifespan and advance our understanding of the regulation of ACE2 and cell death programs in the mammalian lung. Furthermore, our work provides the framework for translation of apoptosis modulating drugs as novel treatments for COVID-19.
Keywords	covid19
Language	English
Publishing date	2020-09-13
Publisher	Cold Spring Harbor Laboratory
Document type	Article ; Online
DOI	10.1101/2020.09.13.276923
Database	COVID19

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Article: Patterned Collagen Fibers Orient Branching Mammary Epithelium through Distinct Signaling Modules

Brownfield, Douglas G / Venugopalan, Gautham / Lo, Alvin / Mori, Hidetoshi / Tanner, Kandice / Fletcher, Daniel A / Bissell, Mina J

Current biology. 2013 Apr. 22, v. 23, no. 8

2013

Abstract: For decades, the work of cell and developmental biologists has demonstrated the striking ability of the mesenchyme and the stroma to instruct epithelial form and function in the mammary gland [1–3], but the role of extracellular matrix (ECM) molecules in ...

Abstract	For decades, the work of cell and developmental biologists has demonstrated the striking ability of the mesenchyme and the stroma to instruct epithelial form and function in the mammary gland [1–3], but the role of extracellular matrix (ECM) molecules in mammary pattern specification has not been elucidated. Here, we show that stromal collagen I (Col-I) fibers in the mammary fat pad are axially oriented prior to branching morphogenesis. Upon puberty, the branching epithelium orients along these fibers, thereby adopting a similar axial bias. To establish a causal relationship from Col-I fiber to epithelial orientation, we embedded mammary organoids within axially oriented Col-I fiber gels and observed dramatic epithelial co-orientation. Whereas a constitutively active form of Rac1, a molecule implicated in cell motility, prevented a directional epithelial response to Col-I fiber orientation, inhibition of the RhoA/Rho-associated kinase (ROCK) pathway did not. However, time-lapse studies revealed that, within randomly oriented Col-I matrices, the epithelium axially aligns fibers at branch sites via RhoA/ROCK-mediated contractions. Our data provide an explanation for how the stromal ECM encodes architectural cues for branch orientation as well as how the branching epithelium interprets and reinforces these cues through distinct signaling processes.
Keywords	biologists ; cell movement ; collagen ; epithelium ; extracellular matrix ; gels ; mammary gland function ; morphogenesis ; puberty
Language	English
Dates of publication	2013-0422
Size	p. 703-709.
Publishing place	Elsevier Inc.
Document type	Article
ZDB-ID	1071731-6
ISSN	1879-0445 ; 0960-9822
ISSN (online)	1879-0445
ISSN	0960-9822
DOI	10.1016/j.cub.2013.03.032
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Article ; Online: Age-dependent regulation of SARS-CoV-2 cell entry genes and cell death programs correlates with COVID-19 severity.

Inde, Zintis / Croker, Ben A / Yapp, Clarence / Joshi, Gaurav N / Spetz, Johan / Fraser, Cameron / Qin, Xingping / Xu, Le / Deskin, Brian / Ghelfi, Elisa / Webb, Gabrielle / Carlin, Aaron F / Zhu, Yanfang Peipei / Leibel, Sandra L / Garretson, Aaron F / Clark, Alex E / Duran, Jason M / Pretorius, Victor / Crotty-Alexander, Laura E /

Li, Chendi / Lee, Jamie Casey / Sodhi, Chhinder / Hackam, David J / Sun, Xin / Hata, Aaron N / Kobzik, Lester / Miller, Jeffrey / Park, Jin-Ah / Brownfield, Douglas / Jia, Hongpeng / Sarosiek, Kristopher A

Science advances

2021 Volume 7, Issue 34

Abstract: Novel coronavirus disease 2019 (COVID-19) severity is highly variable, with pediatric patients typically experiencing less severe infection than adults and especially the elderly. The basis for this difference is unclear. We find that mRNA and protein ... ...

Abstract	Novel coronavirus disease 2019 (COVID-19) severity is highly variable, with pediatric patients typically experiencing less severe infection than adults and especially the elderly. The basis for this difference is unclear. We find that mRNA and protein expression of angiotensin-converting enzyme 2 (ACE2), the cell entry receptor for the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that causes COVID-19, increases with advancing age in distal lung epithelial cells. However, in humans, ACE2 expression exhibits high levels of intra- and interindividual heterogeneity. Further, cells infected with SARS-CoV-2 experience endoplasmic reticulum stress, triggering an unfolded protein response and caspase-mediated apoptosis, a natural host defense system that halts virion production. Apoptosis of infected cells can be selectively induced by treatment with apoptosis-modulating BH3 mimetic drugs. Notably, epithelial cells within young lungs and airways are more primed to undergo apoptosis than those in adults, which may naturally hinder virion production and support milder COVID-19 severity.
MeSH term(s)	Age Factors ; Aged ; Angiotensin-Converting Enzyme 2/genetics ; Angiotensin-Converting Enzyme 2/metabolism ; Animals ; Apoptosis/genetics ; COVID-19/genetics ; COVID-19/metabolism ; COVID-19/virology ; Cells, Cultured ; Chlorocebus aethiops ; Female ; Gene Expression Profiling/methods ; Humans ; Infant ; Lung/cytology ; Lung/metabolism ; Lung/virology ; Male ; Mice, Inbred C57BL ; Middle Aged ; SARS-CoV-2/physiology ; Severity of Illness Index ; Vero Cells ; Virus Internalization ; Mice
Chemical Substances	Angiotensin-Converting Enzyme 2 (EC 3.4.17.23)
Language	English
Publishing date	2021-08-18
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2810933-8
ISSN	2375-2548 ; 2375-2548
ISSN (online)	2375-2548
ISSN	2375-2548
DOI	10.1126/sciadv.abf8609
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Article ; Online: Patterned collagen fibers orient branching mammary epithelium through distinct signaling modules.

Brownfield, Douglas G / Venugopalan, Gautham / Lo, Alvin / Mori, Hidetoshi / Tanner, Kandice / Fletcher, Daniel A / Bissell, Mina J

Current biology : CB

2013 Volume 23, Issue 8, Page(s) 703–709

Abstract: For decades, the work of cell and developmental biologists has demonstrated the striking ability of the mesenchyme and the stroma to instruct epithelial form and function in the mammary gland, but the role of extracellular matrix (ECM) molecules in ... ...

Abstract	For decades, the work of cell and developmental biologists has demonstrated the striking ability of the mesenchyme and the stroma to instruct epithelial form and function in the mammary gland, but the role of extracellular matrix (ECM) molecules in mammary pattern specification has not been elucidated. Here, we show that stromal collagen I (Col-I) fibers in the mammary fat pad are axially oriented prior to branching morphogenesis. Upon puberty, the branching epithelium orients along these fibers, thereby adopting a similar axial bias. To establish a causal relationship from Col-I fiber to epithelial orientation, we embedded mammary organoids within axially oriented Col-I fiber gels and observed dramatic epithelial co-orientation. Whereas a constitutively active form of Rac1, a molecule implicated in cell motility, prevented a directional epithelial response to Col-I fiber orientation, inhibition of the RhoA/Rho-associated kinase (ROCK) pathway did not. However, time-lapse studies revealed that, within randomly oriented Col-I matrices, the epithelium axially aligns fibers at branch sites via RhoA/ROCK-mediated contractions. Our data provide an explanation for how the stromal ECM encodes architectural cues for branch orientation as well as how the branching epithelium interprets and reinforces these cues through distinct signaling processes.
MeSH term(s)	Animals ; Collagen Type I/metabolism ; Epithelium/metabolism ; Extracellular Matrix/metabolism ; Female ; Mammary Glands, Animal/metabolism ; Mesoderm/metabolism ; Mice ; Mice, Inbred BALB C ; Microscopy, Confocal ; Neuropeptides/metabolism ; Sexual Maturation ; Signal Transduction ; rac1 GTP-Binding Protein/metabolism ; rho GTP-Binding Proteins/metabolism ; rho-Associated Kinases/metabolism ; rhoA GTP-Binding Protein
Chemical Substances	Collagen Type I ; Neuropeptides ; Rac1 protein, mouse ; rho-Associated Kinases (EC 2.7.11.1) ; RhoA protein, mouse (EC 3.6.5.2) ; rac1 GTP-Binding Protein (EC 3.6.5.2) ; rho GTP-Binding Proteins (EC 3.6.5.2) ; rhoA GTP-Binding Protein (EC 3.6.5.2)
Language	English
Publishing date	2013-04-04
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	1071731-6
ISSN	1879-0445 ; 0960-9822
ISSN (online)	1879-0445
ISSN	0960-9822
DOI	10.1016/j.cub.2013.03.032
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