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Ying Xia - One of the best experts on this subject based on the ideXlab platform.
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Magnetic resonance imaging study of eye congenital birth defects in mouse model.
Molecular vision, 2017Co-Authors: Jing-huei Lee, Qinghang Meng, Maureen Mongan, Zachary Tucker, Ying XiaAbstract:PURPOSE Embryonic Eyelid Closure is a well-documented morphogenetic episode in mammalian eye development. Detection of Eyelid Closure defect in humans is a major challenge because Eyelid Closure and reopen occur entirely in utero. As a consequence, congenital eye defects that are associated with failure of embryonic Eyelid Closure remain unknown. To fill the gap, we developed a mouse model of defective Eyelid Closure. This preliminary work demonstrates that the magnetic resonance imaging (MRI) approach can be used for the detection of extraocular muscle abnormalities in the mouse model. METHODS Mice with either normal (Map3k1+/- ) or defective (Map3k1-/- ) embryonic Eyelid Closure were used in this study. Images of the extraocular muscles were obtained with a 9.4 T high resolution microimaging MRI system. The extraocular muscles were identified, segmented, and measured in each imaging slice using an in-house program. RESULTS In agreement with histological findings, the imaging data show that mice with defective embryonic Eyelid Closure develop less extraocular muscle than normal mice. In addition, the size of the eyeballs was noticeably reduced in mice with defective embryonic Eyelid Closure. CONCLUSIONS We demonstrated that MRI can potentially be used for the study of extraocular muscle in the mouse model of the eye open-at-birth defect, despite the lack of specificity of muscle group provided by the current imaging resolution.
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Meibomian gland morphogenesis requires developmental Eyelid Closure and lid fusion.
The ocular surface, 2017Co-Authors: Jingjing Wang, Maureen Mongan, Mindy K. Call, Winston Whei-yang Kao, Ying XiaAbstract:Abstract Background and purpose Meibomian glands (MGs) play an important role in the maintenance of ocular surface health, but the mechanisms of their development are still poorly understood. The MGs arise from the epithelium at the junction of Eyelid fusion, raising the possibility that defective Eyelid fusion disturbs the formation of MGs. Methods We examined, histologically and functionally, the development of MGs in mice with either normal or defective Eyelid fusion, displaying eye-closed at birth (ECB) or eye-open at birth (EOB) phenotypes, respectively. Results The Meibomian anlage was detected in the epithelium at the Eyelid fusion junction immediately after birth at postnatal day 0 (PD0), and it extended into the Eyelid stroma at PD1 and started to branch and produce meibum at PD7 in the ECB mice. In contrast, few if any MG structures were detectable in the EOB mice in the early postnatal periods. The Meibomian gland ductile system was seen aligned along the Eyelid margin in the adult ECB mice, but was absent or scarce in that of the EOB mice. While MG abnormalities were found in all EOB mice, the severity varied and corresponded to the position and the size of eye opening but not the genetic defects of the mice. Conclusion Proper Meibomian gland formation and development require Eyelid Closure and fusion.
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Eyelid Closure in embryogenesis is required for ocular adnexa development
Investigative Ophthalmology & Visual Science, 2014Co-Authors: Qinghang Meng, Maureen Mongan, Chiayang Liu, Winston W Y Kao, Vinicius Carreira, Hisaka Kurita, Ying XiaAbstract:PURPOSE Mammalian eye development requires temporary fusion of the upper and lower Eyelids in embryogenesis. Failure of lid Closure in mice leads to an eye open at birth (EOB) phenotype. Many genetic mutant strains develop this phenotype and studies of the mutants lead to a better understanding of the signaling mechanisms of morphogenesis. The present study investigates the roles of lid Closure in eye development. METHODS Seven mutant mouse strains were generated by different gene ablation strategies that inactivated distinct signaling pathways. These mice, including systemic ablation of Map3k1 and Dkk2, ocular surface epithelium (OSE) knockout of c-Jun and Egfr, conditional knockout of Shp2 in stratified epithelium (SE), as well as the Map3k1/Jnk1 and Map3k1/Rhoa compound mutants, all exhibited defective Eyelid Closure. The embryonic and postnatal eyes in these mice were characterized by histology and immunohistochemistry. RESULTS Some eye abnormalities, such as smaller lens in the Map3k1-null mice and Harderian gland hypoplasia in the Dkk2-null mice, appeared to be mutant strain-specific, whereas other abnormalities were seen in all mutants examined. The common defects included corneal erosion/ulceration, meibomian gland hypoplasia, truncation of the Eyelid tarsal muscles, failure of levator palpebrae superioris (LPS) extension into the upper Eyelid and misplacement of the inferior oblique (IO) muscle and inferior rectus (IR) muscle. The muscle defects were traced to the prenatal fetuses. CONCLUSIONS In addition to providing a protective barrier for the ocular surface, Eyelid Closure in embryogenesis is required for the development of ocular adnexa, including Eyelid and extraocular muscles.
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Epithelial sheet movement requires the cooperation of c-Jun and MAP3K1.
Developmental biology, 2014Co-Authors: Qinghang Meng, Maureen Mongan, Winston W Y Kao, Jingjing Wang, Xiaofang Tang, Jinling Zhang, Ying XiaAbstract:Epithelial sheet movement is an essential morphogenetic process during mouse embryonic Eyelid Closure in which Mitogen-Activated Protein 3 Kinase 1 (MAP3K1) and c-Jun play a critical role. Here we show that MAP3K1 associates with the cytoskeleton, activates Jun N-terminal kinase (JNK) and actin polymerization, and promotes the Eyelid inferior epithelial cell elongation and epithelium protrusion. Following epithelium protrusion, c-Jun begins to express and acts to promote ERK phosphorylation and migration of the protruding epithelial cells. Homozygous deletion of either gene causes defective Eyelid Closure, but non-allelic non-complementation does not occur between Map3k1 and c-Jun and the double heterozygotes have normal Eyelid Closure. Results from this study suggest that MAP3K1 and c-Jun signal through distinct temporal-spatial pathways and that productive epithelium movement for Eyelid Closure requires the consecutive action of MAP3K1-dependent cytoskeleton reorganization followed by c-Jun-mediated migration.
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Mitogen-activated protein kinase kinase kinase 1 (MAP3K1) integrates developmental signals for Eyelid Closure
Proceedings of the National Academy of Sciences of the United States of America, 2011Co-Authors: Esmond Geh, Qinghang Meng, Maureen Mongan, Jingcai Wang, Atsushi Takatori, Yi Zheng, Alvaro Puga, Richard A. Lang, Ying XiaAbstract:Developmental Eyelid Closure is an evolutionarily conserved morphogenetic event requiring proliferation, differentiation, cytoskeleton reorganization, and migration of epithelial cells at the tip of the developing Eyelid. Many signaling events take place during Eyelid Closure, but how the signals converge to regulate the morphogenetic process remains an open and intriguing question. Here we show that mitogen-activated protein kinase kinase kinase 1 (MAP3K1) highly expressed in the developing Eyelid epithelium, forms with c-Jun, a regulatory axis that orchestrates morphogenesis by integrating two different networks of Eyelid Closure signals. A TGF-α/EGFR-RhoA module initiates one of these networks by inducing c-Jun expression which, in a phosphorylation-independent manner, binds to the Map3k1 promoter and causes an increase in MAP3K1 expression. RhoA knockout in the ocular surface epithelium disturbs this network by decreasing MAP3K1 expression, and causes delayed Eyelid Closure in Map3k1 hemizygotes. The second network is initiated by the enzymatic activity of MAP3K1, which phosphorylates and activates a JNK-c-Jun module, leading to AP-1 transactivation and induction of its downstream genes, such as Pai-1. MAP3K1 inactivation reduces AP-1 activity and PAI-1 expression both in cells and developing Eyelids. MAP3K1 is therefore the nexus of an intracrine regulatory loop connecting the TGF-α/EGFR/RhoA-c-Jun and JNK-c-Jun-AP-1 pathways in developmental Eyelid Closure.
Winston W Y Kao - One of the best experts on this subject based on the ideXlab platform.
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Eyelid Closure in embryogenesis is required for ocular adnexa development
Investigative Ophthalmology & Visual Science, 2014Co-Authors: Qinghang Meng, Maureen Mongan, Chiayang Liu, Winston W Y Kao, Vinicius Carreira, Hisaka Kurita, Ying XiaAbstract:PURPOSE Mammalian eye development requires temporary fusion of the upper and lower Eyelids in embryogenesis. Failure of lid Closure in mice leads to an eye open at birth (EOB) phenotype. Many genetic mutant strains develop this phenotype and studies of the mutants lead to a better understanding of the signaling mechanisms of morphogenesis. The present study investigates the roles of lid Closure in eye development. METHODS Seven mutant mouse strains were generated by different gene ablation strategies that inactivated distinct signaling pathways. These mice, including systemic ablation of Map3k1 and Dkk2, ocular surface epithelium (OSE) knockout of c-Jun and Egfr, conditional knockout of Shp2 in stratified epithelium (SE), as well as the Map3k1/Jnk1 and Map3k1/Rhoa compound mutants, all exhibited defective Eyelid Closure. The embryonic and postnatal eyes in these mice were characterized by histology and immunohistochemistry. RESULTS Some eye abnormalities, such as smaller lens in the Map3k1-null mice and Harderian gland hypoplasia in the Dkk2-null mice, appeared to be mutant strain-specific, whereas other abnormalities were seen in all mutants examined. The common defects included corneal erosion/ulceration, meibomian gland hypoplasia, truncation of the Eyelid tarsal muscles, failure of levator palpebrae superioris (LPS) extension into the upper Eyelid and misplacement of the inferior oblique (IO) muscle and inferior rectus (IR) muscle. The muscle defects were traced to the prenatal fetuses. CONCLUSIONS In addition to providing a protective barrier for the ocular surface, Eyelid Closure in embryogenesis is required for the development of ocular adnexa, including Eyelid and extraocular muscles.
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Epithelial sheet movement requires the cooperation of c-Jun and MAP3K1.
Developmental biology, 2014Co-Authors: Qinghang Meng, Maureen Mongan, Winston W Y Kao, Jingjing Wang, Xiaofang Tang, Jinling Zhang, Ying XiaAbstract:Epithelial sheet movement is an essential morphogenetic process during mouse embryonic Eyelid Closure in which Mitogen-Activated Protein 3 Kinase 1 (MAP3K1) and c-Jun play a critical role. Here we show that MAP3K1 associates with the cytoskeleton, activates Jun N-terminal kinase (JNK) and actin polymerization, and promotes the Eyelid inferior epithelial cell elongation and epithelium protrusion. Following epithelium protrusion, c-Jun begins to express and acts to promote ERK phosphorylation and migration of the protruding epithelial cells. Homozygous deletion of either gene causes defective Eyelid Closure, but non-allelic non-complementation does not occur between Map3k1 and c-Jun and the double heterozygotes have normal Eyelid Closure. Results from this study suggest that MAP3K1 and c-Jun signal through distinct temporal-spatial pathways and that productive epithelium movement for Eyelid Closure requires the consecutive action of MAP3K1-dependent cytoskeleton reorganization followed by c-Jun-mediated migration.
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a role for mek kinase 1 in tgf β activin induced epithelium movement and embryonic Eyelid Closure
The EMBO Journal, 2003Co-Authors: Lin Zhang, Wei Wang, Yasuhito Hayashi, James V Jester, David E Birk, Min Gao, Chiayang Liu, Winston W Y Kao, Michael Karin, Ying XiaAbstract:MEKK1-deficient mice show an eye open at birth phenotype caused by impairment in embryonic Eyelid Closure. MEK kinase 1 (MEKK1) is highly expressed in the growing tip of the Eyelid epithelium, which displays loose cell–cell contacts and prominent F-actin fibers in wild-type mice, but compact cell contacts, lack of polymerized actin and a concomitant impairment in c-Jun N-terminal phosphorylation in MEKK1-deficient mice. In cultured keratinocytes, MEKK1 is essential for JNK activation by TGF-β and activin, but not by TGF-α. MEKK1-driven JNK activation is required for actin stress fiber formation, c-Jun phosphorylation and cell migration. However, MEKK1 ablation does not impair other TGF-β/activin functions, such as nuclear translocation of Smad4. These results establish a specific role for the MEKK1–JNK cascade in transmission of TGF-β and activin signals that control epithelial cell movement, providing the mechanistic basis for the regulation of Eyelid Closure by MEKK1. This study also suggests that the signaling mechanisms that control Eyelid Closure in mammals and dorsal Closure in Drosophila are evolutionarily conserved.
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A role for MEK kinase 1 in TGF-β/activin-induced epithelium movement and embryonic Eyelid Closure
The EMBO journal, 2003Co-Authors: Lin Zhang, Wei Wang, Yasuhito Hayashi, James V Jester, David E Birk, Min Gao, Chiayang Liu, Winston W Y Kao, Michael Karin, Ying XiaAbstract:MEKK1-deficient mice show an eye open at birth phenotype caused by impairment in embryonic Eyelid Closure. MEK kinase 1 (MEKK1) is highly expressed in the growing tip of the Eyelid epithelium, which displays loose cell–cell contacts and prominent F-actin fibers in wild-type mice, but compact cell contacts, lack of polymerized actin and a concomitant impairment in c-Jun N-terminal phosphorylation in MEKK1-deficient mice. In cultured keratinocytes, MEKK1 is essential for JNK activation by TGF-β and activin, but not by TGF-α. MEKK1-driven JNK activation is required for actin stress fiber formation, c-Jun phosphorylation and cell migration. However, MEKK1 ablation does not impair other TGF-β/activin functions, such as nuclear translocation of Smad4. These results establish a specific role for the MEKK1–JNK cascade in transmission of TGF-β and activin signals that control epithelial cell movement, providing the mechanistic basis for the regulation of Eyelid Closure by MEKK1. This study also suggests that the signaling mechanisms that control Eyelid Closure in mammals and dorsal Closure in Drosophila are evolutionarily conserved.
James V Jester - One of the best experts on this subject based on the ideXlab platform.
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a role for mek kinase 1 in tgf β activin induced epithelium movement and embryonic Eyelid Closure
The EMBO Journal, 2003Co-Authors: Lin Zhang, Wei Wang, Yasuhito Hayashi, James V Jester, David E Birk, Min Gao, Chiayang Liu, Winston W Y Kao, Michael Karin, Ying XiaAbstract:MEKK1-deficient mice show an eye open at birth phenotype caused by impairment in embryonic Eyelid Closure. MEK kinase 1 (MEKK1) is highly expressed in the growing tip of the Eyelid epithelium, which displays loose cell–cell contacts and prominent F-actin fibers in wild-type mice, but compact cell contacts, lack of polymerized actin and a concomitant impairment in c-Jun N-terminal phosphorylation in MEKK1-deficient mice. In cultured keratinocytes, MEKK1 is essential for JNK activation by TGF-β and activin, but not by TGF-α. MEKK1-driven JNK activation is required for actin stress fiber formation, c-Jun phosphorylation and cell migration. However, MEKK1 ablation does not impair other TGF-β/activin functions, such as nuclear translocation of Smad4. These results establish a specific role for the MEKK1–JNK cascade in transmission of TGF-β and activin signals that control epithelial cell movement, providing the mechanistic basis for the regulation of Eyelid Closure by MEKK1. This study also suggests that the signaling mechanisms that control Eyelid Closure in mammals and dorsal Closure in Drosophila are evolutionarily conserved.
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A role for MEK kinase 1 in TGF-β/activin-induced epithelium movement and embryonic Eyelid Closure
The EMBO journal, 2003Co-Authors: Lin Zhang, Wei Wang, Yasuhito Hayashi, James V Jester, David E Birk, Min Gao, Chiayang Liu, Winston W Y Kao, Michael Karin, Ying XiaAbstract:MEKK1-deficient mice show an eye open at birth phenotype caused by impairment in embryonic Eyelid Closure. MEK kinase 1 (MEKK1) is highly expressed in the growing tip of the Eyelid epithelium, which displays loose cell–cell contacts and prominent F-actin fibers in wild-type mice, but compact cell contacts, lack of polymerized actin and a concomitant impairment in c-Jun N-terminal phosphorylation in MEKK1-deficient mice. In cultured keratinocytes, MEKK1 is essential for JNK activation by TGF-β and activin, but not by TGF-α. MEKK1-driven JNK activation is required for actin stress fiber formation, c-Jun phosphorylation and cell migration. However, MEKK1 ablation does not impair other TGF-β/activin functions, such as nuclear translocation of Smad4. These results establish a specific role for the MEKK1–JNK cascade in transmission of TGF-β and activin signals that control epithelial cell movement, providing the mechanistic basis for the regulation of Eyelid Closure by MEKK1. This study also suggests that the signaling mechanisms that control Eyelid Closure in mammals and dorsal Closure in Drosophila are evolutionarily conserved.
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Effects of Eyelid Closure and disposable and silicone hydrogel extended contact lens wear on rabbit corneal epithelial proliferation.
Investigative ophthalmology & visual science, 2003Co-Authors: Patrick M. Ladage, James V Jester, David H. Ren, Walter M Petroll, Jan P.g. Bergmanson, Harrison D CavanaghAbstract:PURPOSE To examine the rabbit corneal epithelial cell proliferation rate after extended wear of disposable or silicone hydrogel contact lenses or prolonged Eyelid Closure. METHODS One randomly chosen eye of 40 New Zealand White rabbits was assigned to silicone hydrogel contact lens wear (n = 15, SH), disposable hydrogel contact lens wear (n = 6, DH), Eyelid suturing (n = 15, SUT), or no intervention (n = 4). Contralateral eyes served as the control. After 24 hours or 1 week of lens wear, 5-bromo-2-deoxyuridine (BrdU) was injected intravenously to label dividing corneal epithelial cells, and animals were killed 24 hours after injection. Corneas were stained with monoclonal anti-BrdU antibody and FITC-conjugated secondary antibody. A series of continuous digital images of the wholemounted epithelium were collected from the superior to inferior limbus, and the number of BrdU-labeled cell pairs was counted. RESULTS SH, DH, and SUT caused a significant decrease in BrdU-labeled pairs of cells over the entire corneal epithelium at day 2 compared with the number in contralateral control eyes (P < 0.001). One week of SUT or SH caused a significant increase centrally in BrdU-labeled cells (P < 0.01). BrdU labeling at the limbus in all groups was not significantly different from the control. Unexpectedly, the proliferation rate of the control corneas was also significantly affected by contralateral lens wear and suturing. CONCLUSIONS Short-term overnight SH, DH, and SUT all significantly suppressed the cell proliferation rate in the rabbit corneal epithelium. However, adaptation, with central hyperproliferation of cells, appeared to occur at 8 days. The effects of lens wear and Eyelid suturing on the cell proliferation rate in contralateral control eyes suggests a central mechanism that regulates corneal epithelial proliferation.
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Effect of Eyelid Closure and overnight contact lens wear on viability of surface epithelial cells in rabbit cornea
Cornea, 2002Co-Authors: Kazuaki Yamamoto, James V Jester, Patrick M. Ladage, David H. Ren, Walter M Petroll, Harrison D CavanaghAbstract:Purpose. To determine the effects of open, closed eye, and overnight contact lens wear on homeostatic epithelial surface cell death in the rabbit cornea. Methods. One eye of each rabbit was either closed by Eyelid suture or fitted with one of the following test contact lenses: (1) low Dk/t rigid gas permeable (RGP) lens, (2) hyper Dk/t RGP lens, (3) hyper Dk/t soft lens. The other eye served as a control. After 24 hours, whole corneas were carefully excised and immediately stained with a calcein-acetoxymethyl ester-ethidium homodimer viability assay to quantify the number of nonviable surface epithelial cells. In addition, exfoliated corneal epithelial cells were collected with an eye irrigation chamber to determine cell viability. Results. In the normal cornea, open-eye conditions showed significantly more nonviable surface cells in the central cornea than in the periphery (p < 0.05). Overnight wear of all test lenses and Eyelid Closure induced significant decreases in the number of nonviable cells on the central corneal surface compared with controls (p < 0.05). All exfoliated corneal epithelial cells collected by eye irrigation were nonviable. Conclusion. In the rabbit model, overnight contact lens wear significantly downregulated spontaneous epithelial surface cell death independent of lens rigidity or material oxygen transmissibility. These effects were similar to Eyelid Closure without lens wear. Taken together, these results suggest that Eyelid Closure and the physical presence of the contact lens may protect against the shear stress forces exerted by Eyelid blinking, which are believed to cause central surface cell death and subsequent exfoliation.
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Annexin V binding to rabbit corneal epithelial cells following overnight contact lens wear or Eyelid Closure.
The CLAO journal : official publication of the Contact Lens Association of Ophthalmologists Inc, 2002Co-Authors: David H. Ren, James V Jester, Kazuaki Yamamoto, Patrick M. Ladage, Walter M Petroll, Harrison D CavanaghAbstract:Purpose To determine the effects of open or closed eye and overnight contact lens wear on rabbit corneal epithelial surface cell death, detected by annexin V binding to cell surface phosphatidylserine and propidium iodide (PI) double-labeling. Method New Zealand white rabbits (n = 42) weighing 2.5 to 3.5 kg were divided into 7 study groups: hyper Dk/t rigid gas-permeable (RGP) lens; high Dk/t RGP lens; low Dk/t RGP lens; hyper Dk/t soft lens; high Dk/t soft lens; Eyelid Closure; and nictitating membranectomy study group (n = 6 rabbits for each group). Each rabbit was randomly chosen to have either one eye fitted with a test contact lens or both Eyelids sutured closed; the contralateral eye served as a control. Rabbits were humanely sacrificed after 24 hours. Corneal buttons including the limbus were excised and stained with annexin V-FITC and PI to identify the number of nonviable epithelial surface cells. A series of sequential microscopic adjacent fields (200 microm X560 microm) from the inferior limbus to the central cornea were evaluated using epifluorescence microscopy, and the total number of cells stained with annexin V or PI, or both, was counted in each field. Results Nonviable cells (cells with positive staining) were lowest in density at the limbus and gradually increased in numbers towards the central cornea under normal open eye conditions (P 0.05). Overnight wear of hyper Dk/t or high Dk/t RGP soft contact test lenses caused significant decreases in the numbers of nonviable cells on the central corneal surface (P 0.05). Conclusions This study revealed in the rabbit model a gradient of nonviable surface epithelial cells increasing towards the central cornea under open eye conditions and with central suppression of surface cell death following closed eye (no lens) or physiologic contact lens wear. Taken together, the results suggest that Eyelid Closure or contact lens wear may protect the corneal epithelial cells against the shear stress forces exerted by Eyelid blinking, which are believed to drive central epithelial surface cell death and exfoliation. However, under very low oxygen tensions combined with lens effect, such as in low Dk/t RGP lens wear, surface cell death may be accelerated.
Chiayang Liu - One of the best experts on this subject based on the ideXlab platform.
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Eyelid Closure in embryogenesis is required for ocular adnexa development
Investigative Ophthalmology & Visual Science, 2014Co-Authors: Qinghang Meng, Maureen Mongan, Chiayang Liu, Winston W Y Kao, Vinicius Carreira, Hisaka Kurita, Ying XiaAbstract:PURPOSE Mammalian eye development requires temporary fusion of the upper and lower Eyelids in embryogenesis. Failure of lid Closure in mice leads to an eye open at birth (EOB) phenotype. Many genetic mutant strains develop this phenotype and studies of the mutants lead to a better understanding of the signaling mechanisms of morphogenesis. The present study investigates the roles of lid Closure in eye development. METHODS Seven mutant mouse strains were generated by different gene ablation strategies that inactivated distinct signaling pathways. These mice, including systemic ablation of Map3k1 and Dkk2, ocular surface epithelium (OSE) knockout of c-Jun and Egfr, conditional knockout of Shp2 in stratified epithelium (SE), as well as the Map3k1/Jnk1 and Map3k1/Rhoa compound mutants, all exhibited defective Eyelid Closure. The embryonic and postnatal eyes in these mice were characterized by histology and immunohistochemistry. RESULTS Some eye abnormalities, such as smaller lens in the Map3k1-null mice and Harderian gland hypoplasia in the Dkk2-null mice, appeared to be mutant strain-specific, whereas other abnormalities were seen in all mutants examined. The common defects included corneal erosion/ulceration, meibomian gland hypoplasia, truncation of the Eyelid tarsal muscles, failure of levator palpebrae superioris (LPS) extension into the upper Eyelid and misplacement of the inferior oblique (IO) muscle and inferior rectus (IR) muscle. The muscle defects were traced to the prenatal fetuses. CONCLUSIONS In addition to providing a protective barrier for the ocular surface, Eyelid Closure in embryogenesis is required for the development of ocular adnexa, including Eyelid and extraocular muscles.
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a role for mek kinase 1 in tgf β activin induced epithelium movement and embryonic Eyelid Closure
The EMBO Journal, 2003Co-Authors: Lin Zhang, Wei Wang, Yasuhito Hayashi, James V Jester, David E Birk, Min Gao, Chiayang Liu, Winston W Y Kao, Michael Karin, Ying XiaAbstract:MEKK1-deficient mice show an eye open at birth phenotype caused by impairment in embryonic Eyelid Closure. MEK kinase 1 (MEKK1) is highly expressed in the growing tip of the Eyelid epithelium, which displays loose cell–cell contacts and prominent F-actin fibers in wild-type mice, but compact cell contacts, lack of polymerized actin and a concomitant impairment in c-Jun N-terminal phosphorylation in MEKK1-deficient mice. In cultured keratinocytes, MEKK1 is essential for JNK activation by TGF-β and activin, but not by TGF-α. MEKK1-driven JNK activation is required for actin stress fiber formation, c-Jun phosphorylation and cell migration. However, MEKK1 ablation does not impair other TGF-β/activin functions, such as nuclear translocation of Smad4. These results establish a specific role for the MEKK1–JNK cascade in transmission of TGF-β and activin signals that control epithelial cell movement, providing the mechanistic basis for the regulation of Eyelid Closure by MEKK1. This study also suggests that the signaling mechanisms that control Eyelid Closure in mammals and dorsal Closure in Drosophila are evolutionarily conserved.
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A role for MEK kinase 1 in TGF-β/activin-induced epithelium movement and embryonic Eyelid Closure
The EMBO journal, 2003Co-Authors: Lin Zhang, Wei Wang, Yasuhito Hayashi, James V Jester, David E Birk, Min Gao, Chiayang Liu, Winston W Y Kao, Michael Karin, Ying XiaAbstract:MEKK1-deficient mice show an eye open at birth phenotype caused by impairment in embryonic Eyelid Closure. MEK kinase 1 (MEKK1) is highly expressed in the growing tip of the Eyelid epithelium, which displays loose cell–cell contacts and prominent F-actin fibers in wild-type mice, but compact cell contacts, lack of polymerized actin and a concomitant impairment in c-Jun N-terminal phosphorylation in MEKK1-deficient mice. In cultured keratinocytes, MEKK1 is essential for JNK activation by TGF-β and activin, but not by TGF-α. MEKK1-driven JNK activation is required for actin stress fiber formation, c-Jun phosphorylation and cell migration. However, MEKK1 ablation does not impair other TGF-β/activin functions, such as nuclear translocation of Smad4. These results establish a specific role for the MEKK1–JNK cascade in transmission of TGF-β and activin signals that control epithelial cell movement, providing the mechanistic basis for the regulation of Eyelid Closure by MEKK1. This study also suggests that the signaling mechanisms that control Eyelid Closure in mammals and dorsal Closure in Drosophila are evolutionarily conserved.
Lin Zhang - One of the best experts on this subject based on the ideXlab platform.
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a role for mek kinase 1 in tgf β activin induced epithelium movement and embryonic Eyelid Closure
The EMBO Journal, 2003Co-Authors: Lin Zhang, Wei Wang, Yasuhito Hayashi, James V Jester, David E Birk, Min Gao, Chiayang Liu, Winston W Y Kao, Michael Karin, Ying XiaAbstract:MEKK1-deficient mice show an eye open at birth phenotype caused by impairment in embryonic Eyelid Closure. MEK kinase 1 (MEKK1) is highly expressed in the growing tip of the Eyelid epithelium, which displays loose cell–cell contacts and prominent F-actin fibers in wild-type mice, but compact cell contacts, lack of polymerized actin and a concomitant impairment in c-Jun N-terminal phosphorylation in MEKK1-deficient mice. In cultured keratinocytes, MEKK1 is essential for JNK activation by TGF-β and activin, but not by TGF-α. MEKK1-driven JNK activation is required for actin stress fiber formation, c-Jun phosphorylation and cell migration. However, MEKK1 ablation does not impair other TGF-β/activin functions, such as nuclear translocation of Smad4. These results establish a specific role for the MEKK1–JNK cascade in transmission of TGF-β and activin signals that control epithelial cell movement, providing the mechanistic basis for the regulation of Eyelid Closure by MEKK1. This study also suggests that the signaling mechanisms that control Eyelid Closure in mammals and dorsal Closure in Drosophila are evolutionarily conserved.
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A role for MEK kinase 1 in TGF-β/activin-induced epithelium movement and embryonic Eyelid Closure
The EMBO journal, 2003Co-Authors: Lin Zhang, Wei Wang, Yasuhito Hayashi, James V Jester, David E Birk, Min Gao, Chiayang Liu, Winston W Y Kao, Michael Karin, Ying XiaAbstract:MEKK1-deficient mice show an eye open at birth phenotype caused by impairment in embryonic Eyelid Closure. MEK kinase 1 (MEKK1) is highly expressed in the growing tip of the Eyelid epithelium, which displays loose cell–cell contacts and prominent F-actin fibers in wild-type mice, but compact cell contacts, lack of polymerized actin and a concomitant impairment in c-Jun N-terminal phosphorylation in MEKK1-deficient mice. In cultured keratinocytes, MEKK1 is essential for JNK activation by TGF-β and activin, but not by TGF-α. MEKK1-driven JNK activation is required for actin stress fiber formation, c-Jun phosphorylation and cell migration. However, MEKK1 ablation does not impair other TGF-β/activin functions, such as nuclear translocation of Smad4. These results establish a specific role for the MEKK1–JNK cascade in transmission of TGF-β and activin signals that control epithelial cell movement, providing the mechanistic basis for the regulation of Eyelid Closure by MEKK1. This study also suggests that the signaling mechanisms that control Eyelid Closure in mammals and dorsal Closure in Drosophila are evolutionarily conserved.
