Deficiency of the bZIP transcription factors Mafg and Mafk causes misexpression of genes in distinct pathways and results in lens embryonic developmental defects

Deficiency of the small Maf proteins Mafg and Mafk cause multiple defects, namely, progressive neuronal degeneration, cataract, thrombocytopenia and mid-gestational/perinatal lethality. Previous data shows Mafg−/−:Mafk+/- compound knockout (KO) mice exhibit cataracts age 4-months onward. Strikingly, Mafg−/−:Mafk−/− double KO mice develop lens defects significantly early in life, during embryogenesis, but the pathobiology of these defects is unknown, and is addressed here. At embryonic day (E)16.5, the epithelium of lens in Mafg−/−:Mafk−/− animals appears abnormally multilayered as demonstrated by E-cadherin and nuclear staining. Additionally, Mafg−/−:Mafk−/− lenses exhibit abnormal distribution of F-actin near the “fulcrum” region where epithelial cells undergo apical constriction prior to elongation and reorientation as early differentiating fiber cells. To identify the underlying molecular changes, we performed high-throughput RNA-sequencing of E16.5 Mafg−/−:Mafk−/− lenses and identified a cohort of differentially expressed genes that were further prioritized using stringent filtering criteria and validated by RT-qPCR. Several key factors associated with the cytoskeleton, cell cycle or extracellular matrix (e.g., Cdk1, Cdkn1c, Camsap1, Col3a1, Map3k12, Sipa1l1) were mis-expressed in Mafg−/−:Mafk−/− lenses. Further, the congenital cataract-linked extracellular matrix peroxidase Pxdn was significantly overexpressed in Mafg−/−:Mafk−/− lenses, which may cause abnormal cell morphology. These data also identified the ephrin signaling receptor Epha5 to be reduced in Mafg−/−:Mafk−/− lenses. This likely contributes to the Mafg−/−:Mafk−/− multilayered lens epithelium pathology, as loss of an ephrin ligand, Efna5 (ephrin-A5), causes similar lens defects. Together, these findings uncover a novel early function of Mafg and Mafk in lens development and identify their new downstream regulatory relationships with key cellular factors. Ausführliche Beschreibung

Gespeichert in:

Autor*in:	Shaili D. Patel [verfasserIn] Deepti Anand [verfasserIn] Hozumi Motohashi [verfasserIn] Fumiki Katsuoka [verfasserIn] Masayuki Yamamoto [verfasserIn] Salil A. Lachke [verfasserIn]

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2022

Schlagwörter:	lens MAFG MAFK transcription development epithelium

Übergeordnetes Werk:	In: Frontiers in Cell and Developmental Biology - Frontiers Media S.A., 2014, 10(2022)
Übergeordnetes Werk:	volume:10 ; year:2022

Links:	Link aufrufen Link aufrufen Link aufrufen Journal toc

DOI / URN:	10.3389/fcell.2022.981893

Katalog-ID:	DOAJ024225193

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allfields	10.3389/fcell.2022.981893 doi (DE-627)DOAJ024225193 (DE-599)DOAJ8dd132b4b3bc435c9b2314fc16bca91d DE-627 ger DE-627 rakwb eng QH301-705.5 Shaili D. Patel verfasserin aut Deficiency of the bZIP transcription factors Mafg and Mafk causes misexpression of genes in distinct pathways and results in lens embryonic developmental defects 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Deficiency of the small Maf proteins Mafg and Mafk cause multiple defects, namely, progressive neuronal degeneration, cataract, thrombocytopenia and mid-gestational/perinatal lethality. Previous data shows Mafg−/−:Mafk+/- compound knockout (KO) mice exhibit cataracts age 4-months onward. Strikingly, Mafg−/−:Mafk−/− double KO mice develop lens defects significantly early in life, during embryogenesis, but the pathobiology of these defects is unknown, and is addressed here. At embryonic day (E)16.5, the epithelium of lens in Mafg−/−:Mafk−/− animals appears abnormally multilayered as demonstrated by E-cadherin and nuclear staining. Additionally, Mafg−/−:Mafk−/− lenses exhibit abnormal distribution of F-actin near the “fulcrum” region where epithelial cells undergo apical constriction prior to elongation and reorientation as early differentiating fiber cells. To identify the underlying molecular changes, we performed high-throughput RNA-sequencing of E16.5 Mafg−/−:Mafk−/− lenses and identified a cohort of differentially expressed genes that were further prioritized using stringent filtering criteria and validated by RT-qPCR. Several key factors associated with the cytoskeleton, cell cycle or extracellular matrix (e.g., Cdk1, Cdkn1c, Camsap1, Col3a1, Map3k12, Sipa1l1) were mis-expressed in Mafg−/−:Mafk−/− lenses. Further, the congenital cataract-linked extracellular matrix peroxidase Pxdn was significantly overexpressed in Mafg−/−:Mafk−/− lenses, which may cause abnormal cell morphology. These data also identified the ephrin signaling receptor Epha5 to be reduced in Mafg−/−:Mafk−/− lenses. This likely contributes to the Mafg−/−:Mafk−/− multilayered lens epithelium pathology, as loss of an ephrin ligand, Efna5 (ephrin-A5), causes similar lens defects. Together, these findings uncover a novel early function of Mafg and Mafk in lens development and identify their new downstream regulatory relationships with key cellular factors. lens MAFG MAFK transcription development epithelium Biology (General) Deepti Anand verfasserin aut Hozumi Motohashi verfasserin aut Fumiki Katsuoka verfasserin aut Masayuki Yamamoto verfasserin aut Salil A. Lachke verfasserin aut Salil A. Lachke verfasserin aut In Frontiers in Cell and Developmental Biology Frontiers Media S.A., 2014 10(2022) (DE-627)770398138 (DE-600)2737824-X 2296634X nnns volume:10 year:2022 https://doi.org/10.3389/fcell.2022.981893 kostenfrei https://doaj.org/article/8dd132b4b3bc435c9b2314fc16bca91d kostenfrei https://www.frontiersin.org/articles/10.3389/fcell.2022.981893/full kostenfrei https://doaj.org/toc/2296-634X Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 10 2022
spelling	10.3389/fcell.2022.981893 doi (DE-627)DOAJ024225193 (DE-599)DOAJ8dd132b4b3bc435c9b2314fc16bca91d DE-627 ger DE-627 rakwb eng QH301-705.5 Shaili D. Patel verfasserin aut Deficiency of the bZIP transcription factors Mafg and Mafk causes misexpression of genes in distinct pathways and results in lens embryonic developmental defects 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Deficiency of the small Maf proteins Mafg and Mafk cause multiple defects, namely, progressive neuronal degeneration, cataract, thrombocytopenia and mid-gestational/perinatal lethality. Previous data shows Mafg−/−:Mafk+/- compound knockout (KO) mice exhibit cataracts age 4-months onward. Strikingly, Mafg−/−:Mafk−/− double KO mice develop lens defects significantly early in life, during embryogenesis, but the pathobiology of these defects is unknown, and is addressed here. At embryonic day (E)16.5, the epithelium of lens in Mafg−/−:Mafk−/− animals appears abnormally multilayered as demonstrated by E-cadherin and nuclear staining. Additionally, Mafg−/−:Mafk−/− lenses exhibit abnormal distribution of F-actin near the “fulcrum” region where epithelial cells undergo apical constriction prior to elongation and reorientation as early differentiating fiber cells. To identify the underlying molecular changes, we performed high-throughput RNA-sequencing of E16.5 Mafg−/−:Mafk−/− lenses and identified a cohort of differentially expressed genes that were further prioritized using stringent filtering criteria and validated by RT-qPCR. Several key factors associated with the cytoskeleton, cell cycle or extracellular matrix (e.g., Cdk1, Cdkn1c, Camsap1, Col3a1, Map3k12, Sipa1l1) were mis-expressed in Mafg−/−:Mafk−/− lenses. Further, the congenital cataract-linked extracellular matrix peroxidase Pxdn was significantly overexpressed in Mafg−/−:Mafk−/− lenses, which may cause abnormal cell morphology. These data also identified the ephrin signaling receptor Epha5 to be reduced in Mafg−/−:Mafk−/− lenses. This likely contributes to the Mafg−/−:Mafk−/− multilayered lens epithelium pathology, as loss of an ephrin ligand, Efna5 (ephrin-A5), causes similar lens defects. Together, these findings uncover a novel early function of Mafg and Mafk in lens development and identify their new downstream regulatory relationships with key cellular factors. lens MAFG MAFK transcription development epithelium Biology (General) Deepti Anand verfasserin aut Hozumi Motohashi verfasserin aut Fumiki Katsuoka verfasserin aut Masayuki Yamamoto verfasserin aut Salil A. Lachke verfasserin aut Salil A. Lachke verfasserin aut In Frontiers in Cell and Developmental Biology Frontiers Media S.A., 2014 10(2022) (DE-627)770398138 (DE-600)2737824-X 2296634X nnns volume:10 year:2022 https://doi.org/10.3389/fcell.2022.981893 kostenfrei https://doaj.org/article/8dd132b4b3bc435c9b2314fc16bca91d kostenfrei https://www.frontiersin.org/articles/10.3389/fcell.2022.981893/full kostenfrei https://doaj.org/toc/2296-634X Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 10 2022
allfields_unstemmed	10.3389/fcell.2022.981893 doi (DE-627)DOAJ024225193 (DE-599)DOAJ8dd132b4b3bc435c9b2314fc16bca91d DE-627 ger DE-627 rakwb eng QH301-705.5 Shaili D. Patel verfasserin aut Deficiency of the bZIP transcription factors Mafg and Mafk causes misexpression of genes in distinct pathways and results in lens embryonic developmental defects 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Deficiency of the small Maf proteins Mafg and Mafk cause multiple defects, namely, progressive neuronal degeneration, cataract, thrombocytopenia and mid-gestational/perinatal lethality. Previous data shows Mafg−/−:Mafk+/- compound knockout (KO) mice exhibit cataracts age 4-months onward. Strikingly, Mafg−/−:Mafk−/− double KO mice develop lens defects significantly early in life, during embryogenesis, but the pathobiology of these defects is unknown, and is addressed here. At embryonic day (E)16.5, the epithelium of lens in Mafg−/−:Mafk−/− animals appears abnormally multilayered as demonstrated by E-cadherin and nuclear staining. Additionally, Mafg−/−:Mafk−/− lenses exhibit abnormal distribution of F-actin near the “fulcrum” region where epithelial cells undergo apical constriction prior to elongation and reorientation as early differentiating fiber cells. To identify the underlying molecular changes, we performed high-throughput RNA-sequencing of E16.5 Mafg−/−:Mafk−/− lenses and identified a cohort of differentially expressed genes that were further prioritized using stringent filtering criteria and validated by RT-qPCR. Several key factors associated with the cytoskeleton, cell cycle or extracellular matrix (e.g., Cdk1, Cdkn1c, Camsap1, Col3a1, Map3k12, Sipa1l1) were mis-expressed in Mafg−/−:Mafk−/− lenses. Further, the congenital cataract-linked extracellular matrix peroxidase Pxdn was significantly overexpressed in Mafg−/−:Mafk−/− lenses, which may cause abnormal cell morphology. These data also identified the ephrin signaling receptor Epha5 to be reduced in Mafg−/−:Mafk−/− lenses. This likely contributes to the Mafg−/−:Mafk−/− multilayered lens epithelium pathology, as loss of an ephrin ligand, Efna5 (ephrin-A5), causes similar lens defects. Together, these findings uncover a novel early function of Mafg and Mafk in lens development and identify their new downstream regulatory relationships with key cellular factors. lens MAFG MAFK transcription development epithelium Biology (General) Deepti Anand verfasserin aut Hozumi Motohashi verfasserin aut Fumiki Katsuoka verfasserin aut Masayuki Yamamoto verfasserin aut Salil A. Lachke verfasserin aut Salil A. Lachke verfasserin aut In Frontiers in Cell and Developmental Biology Frontiers Media S.A., 2014 10(2022) (DE-627)770398138 (DE-600)2737824-X 2296634X nnns volume:10 year:2022 https://doi.org/10.3389/fcell.2022.981893 kostenfrei https://doaj.org/article/8dd132b4b3bc435c9b2314fc16bca91d kostenfrei https://www.frontiersin.org/articles/10.3389/fcell.2022.981893/full kostenfrei https://doaj.org/toc/2296-634X Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 10 2022
allfieldsGer	10.3389/fcell.2022.981893 doi (DE-627)DOAJ024225193 (DE-599)DOAJ8dd132b4b3bc435c9b2314fc16bca91d DE-627 ger DE-627 rakwb eng QH301-705.5 Shaili D. Patel verfasserin aut Deficiency of the bZIP transcription factors Mafg and Mafk causes misexpression of genes in distinct pathways and results in lens embryonic developmental defects 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Deficiency of the small Maf proteins Mafg and Mafk cause multiple defects, namely, progressive neuronal degeneration, cataract, thrombocytopenia and mid-gestational/perinatal lethality. Previous data shows Mafg−/−:Mafk+/- compound knockout (KO) mice exhibit cataracts age 4-months onward. Strikingly, Mafg−/−:Mafk−/− double KO mice develop lens defects significantly early in life, during embryogenesis, but the pathobiology of these defects is unknown, and is addressed here. At embryonic day (E)16.5, the epithelium of lens in Mafg−/−:Mafk−/− animals appears abnormally multilayered as demonstrated by E-cadherin and nuclear staining. Additionally, Mafg−/−:Mafk−/− lenses exhibit abnormal distribution of F-actin near the “fulcrum” region where epithelial cells undergo apical constriction prior to elongation and reorientation as early differentiating fiber cells. To identify the underlying molecular changes, we performed high-throughput RNA-sequencing of E16.5 Mafg−/−:Mafk−/− lenses and identified a cohort of differentially expressed genes that were further prioritized using stringent filtering criteria and validated by RT-qPCR. Several key factors associated with the cytoskeleton, cell cycle or extracellular matrix (e.g., Cdk1, Cdkn1c, Camsap1, Col3a1, Map3k12, Sipa1l1) were mis-expressed in Mafg−/−:Mafk−/− lenses. Further, the congenital cataract-linked extracellular matrix peroxidase Pxdn was significantly overexpressed in Mafg−/−:Mafk−/− lenses, which may cause abnormal cell morphology. These data also identified the ephrin signaling receptor Epha5 to be reduced in Mafg−/−:Mafk−/− lenses. This likely contributes to the Mafg−/−:Mafk−/− multilayered lens epithelium pathology, as loss of an ephrin ligand, Efna5 (ephrin-A5), causes similar lens defects. Together, these findings uncover a novel early function of Mafg and Mafk in lens development and identify their new downstream regulatory relationships with key cellular factors. lens MAFG MAFK transcription development epithelium Biology (General) Deepti Anand verfasserin aut Hozumi Motohashi verfasserin aut Fumiki Katsuoka verfasserin aut Masayuki Yamamoto verfasserin aut Salil A. Lachke verfasserin aut Salil A. Lachke verfasserin aut In Frontiers in Cell and Developmental Biology Frontiers Media S.A., 2014 10(2022) (DE-627)770398138 (DE-600)2737824-X 2296634X nnns volume:10 year:2022 https://doi.org/10.3389/fcell.2022.981893 kostenfrei https://doaj.org/article/8dd132b4b3bc435c9b2314fc16bca91d kostenfrei https://www.frontiersin.org/articles/10.3389/fcell.2022.981893/full kostenfrei https://doaj.org/toc/2296-634X Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 10 2022
allfieldsSound	10.3389/fcell.2022.981893 doi (DE-627)DOAJ024225193 (DE-599)DOAJ8dd132b4b3bc435c9b2314fc16bca91d DE-627 ger DE-627 rakwb eng QH301-705.5 Shaili D. Patel verfasserin aut Deficiency of the bZIP transcription factors Mafg and Mafk causes misexpression of genes in distinct pathways and results in lens embryonic developmental defects 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Deficiency of the small Maf proteins Mafg and Mafk cause multiple defects, namely, progressive neuronal degeneration, cataract, thrombocytopenia and mid-gestational/perinatal lethality. Previous data shows Mafg−/−:Mafk+/- compound knockout (KO) mice exhibit cataracts age 4-months onward. Strikingly, Mafg−/−:Mafk−/− double KO mice develop lens defects significantly early in life, during embryogenesis, but the pathobiology of these defects is unknown, and is addressed here. At embryonic day (E)16.5, the epithelium of lens in Mafg−/−:Mafk−/− animals appears abnormally multilayered as demonstrated by E-cadherin and nuclear staining. Additionally, Mafg−/−:Mafk−/− lenses exhibit abnormal distribution of F-actin near the “fulcrum” region where epithelial cells undergo apical constriction prior to elongation and reorientation as early differentiating fiber cells. To identify the underlying molecular changes, we performed high-throughput RNA-sequencing of E16.5 Mafg−/−:Mafk−/− lenses and identified a cohort of differentially expressed genes that were further prioritized using stringent filtering criteria and validated by RT-qPCR. Several key factors associated with the cytoskeleton, cell cycle or extracellular matrix (e.g., Cdk1, Cdkn1c, Camsap1, Col3a1, Map3k12, Sipa1l1) were mis-expressed in Mafg−/−:Mafk−/− lenses. Further, the congenital cataract-linked extracellular matrix peroxidase Pxdn was significantly overexpressed in Mafg−/−:Mafk−/− lenses, which may cause abnormal cell morphology. These data also identified the ephrin signaling receptor Epha5 to be reduced in Mafg−/−:Mafk−/− lenses. This likely contributes to the Mafg−/−:Mafk−/− multilayered lens epithelium pathology, as loss of an ephrin ligand, Efna5 (ephrin-A5), causes similar lens defects. Together, these findings uncover a novel early function of Mafg and Mafk in lens development and identify their new downstream regulatory relationships with key cellular factors. lens MAFG MAFK transcription development epithelium Biology (General) Deepti Anand verfasserin aut Hozumi Motohashi verfasserin aut Fumiki Katsuoka verfasserin aut Masayuki Yamamoto verfasserin aut Salil A. Lachke verfasserin aut Salil A. Lachke verfasserin aut In Frontiers in Cell and Developmental Biology Frontiers Media S.A., 2014 10(2022) (DE-627)770398138 (DE-600)2737824-X 2296634X nnns volume:10 year:2022 https://doi.org/10.3389/fcell.2022.981893 kostenfrei https://doaj.org/article/8dd132b4b3bc435c9b2314fc16bca91d kostenfrei https://www.frontiersin.org/articles/10.3389/fcell.2022.981893/full kostenfrei https://doaj.org/toc/2296-634X Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 10 2022
language	English
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container_title	Frontiers in Cell and Developmental Biology
authorswithroles_txt_mv	Shaili D. Patel @@aut@@ Deepti Anand @@aut@@ Hozumi Motohashi @@aut@@ Fumiki Katsuoka @@aut@@ Masayuki Yamamoto @@aut@@ Salil A. Lachke @@aut@@
publishDateDaySort_date	2022-01-01T00:00:00Z
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callnumber-first	Q - Science
author	Shaili D. Patel
spellingShingle	Shaili D. Patel misc QH301-705.5 misc lens misc MAFG misc MAFK misc transcription misc development misc epithelium misc Biology (General) Deficiency of the bZIP transcription factors Mafg and Mafk causes misexpression of genes in distinct pathways and results in lens embryonic developmental defects
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topic_title	QH301-705.5 Deficiency of the bZIP transcription factors Mafg and Mafk causes misexpression of genes in distinct pathways and results in lens embryonic developmental defects lens MAFG MAFK transcription development epithelium
topic	misc QH301-705.5 misc lens misc MAFG misc MAFK misc transcription misc development misc epithelium misc Biology (General)
topic_unstemmed	misc QH301-705.5 misc lens misc MAFG misc MAFK misc transcription misc development misc epithelium misc Biology (General)
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title	Deficiency of the bZIP transcription factors Mafg and Mafk causes misexpression of genes in distinct pathways and results in lens embryonic developmental defects
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title_full	Deficiency of the bZIP transcription factors Mafg and Mafk causes misexpression of genes in distinct pathways and results in lens embryonic developmental defects
author_sort	Shaili D. Patel
journal	Frontiers in Cell and Developmental Biology
journalStr	Frontiers in Cell and Developmental Biology
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author_browse	Shaili D. Patel Deepti Anand Hozumi Motohashi Fumiki Katsuoka Masayuki Yamamoto Salil A. Lachke
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author-letter	Shaili D. Patel
doi_str_mv	10.3389/fcell.2022.981893
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title_sort	deficiency of the bzip transcription factors mafg and mafk causes misexpression of genes in distinct pathways and results in lens embryonic developmental defects
callnumber	QH301-705.5
title_auth	Deficiency of the bZIP transcription factors Mafg and Mafk causes misexpression of genes in distinct pathways and results in lens embryonic developmental defects
abstract	Deficiency of the small Maf proteins Mafg and Mafk cause multiple defects, namely, progressive neuronal degeneration, cataract, thrombocytopenia and mid-gestational/perinatal lethality. Previous data shows Mafg−/−:Mafk+/- compound knockout (KO) mice exhibit cataracts age 4-months onward. Strikingly, Mafg−/−:Mafk−/− double KO mice develop lens defects significantly early in life, during embryogenesis, but the pathobiology of these defects is unknown, and is addressed here. At embryonic day (E)16.5, the epithelium of lens in Mafg−/−:Mafk−/− animals appears abnormally multilayered as demonstrated by E-cadherin and nuclear staining. Additionally, Mafg−/−:Mafk−/− lenses exhibit abnormal distribution of F-actin near the “fulcrum” region where epithelial cells undergo apical constriction prior to elongation and reorientation as early differentiating fiber cells. To identify the underlying molecular changes, we performed high-throughput RNA-sequencing of E16.5 Mafg−/−:Mafk−/− lenses and identified a cohort of differentially expressed genes that were further prioritized using stringent filtering criteria and validated by RT-qPCR. Several key factors associated with the cytoskeleton, cell cycle or extracellular matrix (e.g., Cdk1, Cdkn1c, Camsap1, Col3a1, Map3k12, Sipa1l1) were mis-expressed in Mafg−/−:Mafk−/− lenses. Further, the congenital cataract-linked extracellular matrix peroxidase Pxdn was significantly overexpressed in Mafg−/−:Mafk−/− lenses, which may cause abnormal cell morphology. These data also identified the ephrin signaling receptor Epha5 to be reduced in Mafg−/−:Mafk−/− lenses. This likely contributes to the Mafg−/−:Mafk−/− multilayered lens epithelium pathology, as loss of an ephrin ligand, Efna5 (ephrin-A5), causes similar lens defects. Together, these findings uncover a novel early function of Mafg and Mafk in lens development and identify their new downstream regulatory relationships with key cellular factors.
abstractGer	Deficiency of the small Maf proteins Mafg and Mafk cause multiple defects, namely, progressive neuronal degeneration, cataract, thrombocytopenia and mid-gestational/perinatal lethality. Previous data shows Mafg−/−:Mafk+/- compound knockout (KO) mice exhibit cataracts age 4-months onward. Strikingly, Mafg−/−:Mafk−/− double KO mice develop lens defects significantly early in life, during embryogenesis, but the pathobiology of these defects is unknown, and is addressed here. At embryonic day (E)16.5, the epithelium of lens in Mafg−/−:Mafk−/− animals appears abnormally multilayered as demonstrated by E-cadherin and nuclear staining. Additionally, Mafg−/−:Mafk−/− lenses exhibit abnormal distribution of F-actin near the “fulcrum” region where epithelial cells undergo apical constriction prior to elongation and reorientation as early differentiating fiber cells. To identify the underlying molecular changes, we performed high-throughput RNA-sequencing of E16.5 Mafg−/−:Mafk−/− lenses and identified a cohort of differentially expressed genes that were further prioritized using stringent filtering criteria and validated by RT-qPCR. Several key factors associated with the cytoskeleton, cell cycle or extracellular matrix (e.g., Cdk1, Cdkn1c, Camsap1, Col3a1, Map3k12, Sipa1l1) were mis-expressed in Mafg−/−:Mafk−/− lenses. Further, the congenital cataract-linked extracellular matrix peroxidase Pxdn was significantly overexpressed in Mafg−/−:Mafk−/− lenses, which may cause abnormal cell morphology. These data also identified the ephrin signaling receptor Epha5 to be reduced in Mafg−/−:Mafk−/− lenses. This likely contributes to the Mafg−/−:Mafk−/− multilayered lens epithelium pathology, as loss of an ephrin ligand, Efna5 (ephrin-A5), causes similar lens defects. Together, these findings uncover a novel early function of Mafg and Mafk in lens development and identify their new downstream regulatory relationships with key cellular factors.
abstract_unstemmed	Deficiency of the small Maf proteins Mafg and Mafk cause multiple defects, namely, progressive neuronal degeneration, cataract, thrombocytopenia and mid-gestational/perinatal lethality. Previous data shows Mafg−/−:Mafk+/- compound knockout (KO) mice exhibit cataracts age 4-months onward. Strikingly, Mafg−/−:Mafk−/− double KO mice develop lens defects significantly early in life, during embryogenesis, but the pathobiology of these defects is unknown, and is addressed here. At embryonic day (E)16.5, the epithelium of lens in Mafg−/−:Mafk−/− animals appears abnormally multilayered as demonstrated by E-cadherin and nuclear staining. Additionally, Mafg−/−:Mafk−/− lenses exhibit abnormal distribution of F-actin near the “fulcrum” region where epithelial cells undergo apical constriction prior to elongation and reorientation as early differentiating fiber cells. To identify the underlying molecular changes, we performed high-throughput RNA-sequencing of E16.5 Mafg−/−:Mafk−/− lenses and identified a cohort of differentially expressed genes that were further prioritized using stringent filtering criteria and validated by RT-qPCR. Several key factors associated with the cytoskeleton, cell cycle or extracellular matrix (e.g., Cdk1, Cdkn1c, Camsap1, Col3a1, Map3k12, Sipa1l1) were mis-expressed in Mafg−/−:Mafk−/− lenses. Further, the congenital cataract-linked extracellular matrix peroxidase Pxdn was significantly overexpressed in Mafg−/−:Mafk−/− lenses, which may cause abnormal cell morphology. These data also identified the ephrin signaling receptor Epha5 to be reduced in Mafg−/−:Mafk−/− lenses. This likely contributes to the Mafg−/−:Mafk−/− multilayered lens epithelium pathology, as loss of an ephrin ligand, Efna5 (ephrin-A5), causes similar lens defects. Together, these findings uncover a novel early function of Mafg and Mafk in lens development and identify their new downstream regulatory relationships with key cellular factors.
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title_short	Deficiency of the bZIP transcription factors Mafg and Mafk causes misexpression of genes in distinct pathways and results in lens embryonic developmental defects
url	https://doi.org/10.3389/fcell.2022.981893 https://doaj.org/article/8dd132b4b3bc435c9b2314fc16bca91d https://www.frontiersin.org/articles/10.3389/fcell.2022.981893/full https://doaj.org/toc/2296-634X
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author2	Deepti Anand Hozumi Motohashi Fumiki Katsuoka Masayuki Yamamoto Salil A. Lachke
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up_date	2024-07-03T21:52:47.974Z
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