ATXN10 Is Required for Embryonic Heart Development and Maintenance of Epithelial Cell Phenotypes in the Adult Kidney and Pancreas

Atxn10 is a gene known for its role in cytokinesis and is associated with spinocerebellar ataxia (SCA10), a slowly progressing cerebellar syndrome caused by an intragenic pentanucleotide repeat expansion. Atxn10 is also implicated in the ciliopathy syndromes nephronophthisis (NPHP) and Joubert syndr...
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Autor*in:	Melissa R. Bentley-Ford [verfasserIn] Reagan S. Andersen [verfasserIn] Mandy J. Croyle [verfasserIn] Courtney J. Haycraft [verfasserIn] Kelsey R. Clearman [verfasserIn] Jeremy B. Foote [verfasserIn] Jeremy F. Reiter [verfasserIn] Bradley K. Yoder [verfasserIn]

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2021

Schlagwörter:	ataxin 10 (ATXN10) epithelial-to-mesenchymal transition (EMT) cilia acinar-to-ductal metaplasia (ADM) heart kidney

Übergeordnetes Werk:	In: Frontiers in Cell and Developmental Biology - Frontiers Media S.A., 2014, 9(2021)
Übergeordnetes Werk:	volume:9 ; year:2021

Links:	Link aufrufen Link aufrufen Link aufrufen Journal toc

DOI / URN:	10.3389/fcell.2021.705182

Katalog-ID:	DOAJ019762267

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allfields	10.3389/fcell.2021.705182 doi (DE-627)DOAJ019762267 (DE-599)DOAJ9d7d5542e32b4071b4aa9da8b86dd96c DE-627 ger DE-627 rakwb eng QH301-705.5 Melissa R. Bentley-Ford verfasserin aut ATXN10 Is Required for Embryonic Heart Development and Maintenance of Epithelial Cell Phenotypes in the Adult Kidney and Pancreas 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Atxn10 is a gene known for its role in cytokinesis and is associated with spinocerebellar ataxia (SCA10), a slowly progressing cerebellar syndrome caused by an intragenic pentanucleotide repeat expansion. Atxn10 is also implicated in the ciliopathy syndromes nephronophthisis (NPHP) and Joubert syndrome (JBTS), which are caused by the disruption of cilia function leading to nephron loss, impaired renal function, and cerebellar hypoplasia. How Atxn10 disruption contributes to these disorders remains unknown. Here, we generated Atxn10 congenital and conditional mutant mouse models. Our data indicate that while ATXN10 protein can be detected around the base of the cilium as well as in the cytosol, its loss does not cause overt changes in cilia formation or morphology. Congenital loss of Atxn10 results in embryonic lethality around E10.5 associated with pericardial effusion and loss of trabeculation. Similarly, tissue-specific loss of ATXN10 in the developing endothelium (Tie2-Cre) and myocardium (cTnT-Cre) also results in embryonic lethality with severe cardiac malformations occurring in the latter. Using an inducible Cagg-CreER to disrupt ATXN10 systemically at postnatal stages, we show that ATXN10 is also required for survival in adult mice. Loss of ATXN10 results in severe pancreatic and renal abnormalities leading to lethality within a few weeks post ATXN10 deletion in adult mice. Evaluation of these phenotypes further identified rapid epithelial-to-mesenchymal transition (EMT) in these tissues. In the pancreas, the phenotype includes signs of both acinar to ductal metaplasia and EMT with aberrant cilia formation and severe defects in glucose homeostasis related to pancreatic insufficiency or defects in feeding or nutrient intake. Collectively, this study identifies ATXN10 as an essential protein for survival. ataxin 10 (ATXN10) epithelial-to-mesenchymal transition (EMT) cilia acinar-to-ductal metaplasia (ADM) heart kidney Biology (General) Reagan S. Andersen verfasserin aut Mandy J. Croyle verfasserin aut Courtney J. Haycraft verfasserin aut Kelsey R. Clearman verfasserin aut Jeremy B. Foote verfasserin aut Jeremy F. Reiter verfasserin aut Jeremy F. Reiter verfasserin aut Bradley K. Yoder verfasserin aut In Frontiers in Cell and Developmental Biology Frontiers Media S.A., 2014 9(2021) (DE-627)770398138 (DE-600)2737824-X 2296634X nnns volume:9 year:2021 https://doi.org/10.3389/fcell.2021.705182 kostenfrei https://doaj.org/article/9d7d5542e32b4071b4aa9da8b86dd96c kostenfrei https://www.frontiersin.org/articles/10.3389/fcell.2021.705182/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 9 2021
spelling	10.3389/fcell.2021.705182 doi (DE-627)DOAJ019762267 (DE-599)DOAJ9d7d5542e32b4071b4aa9da8b86dd96c DE-627 ger DE-627 rakwb eng QH301-705.5 Melissa R. Bentley-Ford verfasserin aut ATXN10 Is Required for Embryonic Heart Development and Maintenance of Epithelial Cell Phenotypes in the Adult Kidney and Pancreas 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Atxn10 is a gene known for its role in cytokinesis and is associated with spinocerebellar ataxia (SCA10), a slowly progressing cerebellar syndrome caused by an intragenic pentanucleotide repeat expansion. Atxn10 is also implicated in the ciliopathy syndromes nephronophthisis (NPHP) and Joubert syndrome (JBTS), which are caused by the disruption of cilia function leading to nephron loss, impaired renal function, and cerebellar hypoplasia. How Atxn10 disruption contributes to these disorders remains unknown. Here, we generated Atxn10 congenital and conditional mutant mouse models. Our data indicate that while ATXN10 protein can be detected around the base of the cilium as well as in the cytosol, its loss does not cause overt changes in cilia formation or morphology. Congenital loss of Atxn10 results in embryonic lethality around E10.5 associated with pericardial effusion and loss of trabeculation. Similarly, tissue-specific loss of ATXN10 in the developing endothelium (Tie2-Cre) and myocardium (cTnT-Cre) also results in embryonic lethality with severe cardiac malformations occurring in the latter. Using an inducible Cagg-CreER to disrupt ATXN10 systemically at postnatal stages, we show that ATXN10 is also required for survival in adult mice. Loss of ATXN10 results in severe pancreatic and renal abnormalities leading to lethality within a few weeks post ATXN10 deletion in adult mice. Evaluation of these phenotypes further identified rapid epithelial-to-mesenchymal transition (EMT) in these tissues. In the pancreas, the phenotype includes signs of both acinar to ductal metaplasia and EMT with aberrant cilia formation and severe defects in glucose homeostasis related to pancreatic insufficiency or defects in feeding or nutrient intake. Collectively, this study identifies ATXN10 as an essential protein for survival. ataxin 10 (ATXN10) epithelial-to-mesenchymal transition (EMT) cilia acinar-to-ductal metaplasia (ADM) heart kidney Biology (General) Reagan S. Andersen verfasserin aut Mandy J. Croyle verfasserin aut Courtney J. Haycraft verfasserin aut Kelsey R. Clearman verfasserin aut Jeremy B. Foote verfasserin aut Jeremy F. Reiter verfasserin aut Jeremy F. Reiter verfasserin aut Bradley K. Yoder verfasserin aut In Frontiers in Cell and Developmental Biology Frontiers Media S.A., 2014 9(2021) (DE-627)770398138 (DE-600)2737824-X 2296634X nnns volume:9 year:2021 https://doi.org/10.3389/fcell.2021.705182 kostenfrei https://doaj.org/article/9d7d5542e32b4071b4aa9da8b86dd96c kostenfrei https://www.frontiersin.org/articles/10.3389/fcell.2021.705182/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 9 2021
allfields_unstemmed	10.3389/fcell.2021.705182 doi (DE-627)DOAJ019762267 (DE-599)DOAJ9d7d5542e32b4071b4aa9da8b86dd96c DE-627 ger DE-627 rakwb eng QH301-705.5 Melissa R. Bentley-Ford verfasserin aut ATXN10 Is Required for Embryonic Heart Development and Maintenance of Epithelial Cell Phenotypes in the Adult Kidney and Pancreas 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Atxn10 is a gene known for its role in cytokinesis and is associated with spinocerebellar ataxia (SCA10), a slowly progressing cerebellar syndrome caused by an intragenic pentanucleotide repeat expansion. Atxn10 is also implicated in the ciliopathy syndromes nephronophthisis (NPHP) and Joubert syndrome (JBTS), which are caused by the disruption of cilia function leading to nephron loss, impaired renal function, and cerebellar hypoplasia. How Atxn10 disruption contributes to these disorders remains unknown. Here, we generated Atxn10 congenital and conditional mutant mouse models. Our data indicate that while ATXN10 protein can be detected around the base of the cilium as well as in the cytosol, its loss does not cause overt changes in cilia formation or morphology. Congenital loss of Atxn10 results in embryonic lethality around E10.5 associated with pericardial effusion and loss of trabeculation. Similarly, tissue-specific loss of ATXN10 in the developing endothelium (Tie2-Cre) and myocardium (cTnT-Cre) also results in embryonic lethality with severe cardiac malformations occurring in the latter. Using an inducible Cagg-CreER to disrupt ATXN10 systemically at postnatal stages, we show that ATXN10 is also required for survival in adult mice. Loss of ATXN10 results in severe pancreatic and renal abnormalities leading to lethality within a few weeks post ATXN10 deletion in adult mice. Evaluation of these phenotypes further identified rapid epithelial-to-mesenchymal transition (EMT) in these tissues. In the pancreas, the phenotype includes signs of both acinar to ductal metaplasia and EMT with aberrant cilia formation and severe defects in glucose homeostasis related to pancreatic insufficiency or defects in feeding or nutrient intake. Collectively, this study identifies ATXN10 as an essential protein for survival. ataxin 10 (ATXN10) epithelial-to-mesenchymal transition (EMT) cilia acinar-to-ductal metaplasia (ADM) heart kidney Biology (General) Reagan S. Andersen verfasserin aut Mandy J. Croyle verfasserin aut Courtney J. Haycraft verfasserin aut Kelsey R. Clearman verfasserin aut Jeremy B. Foote verfasserin aut Jeremy F. Reiter verfasserin aut Jeremy F. Reiter verfasserin aut Bradley K. Yoder verfasserin aut In Frontiers in Cell and Developmental Biology Frontiers Media S.A., 2014 9(2021) (DE-627)770398138 (DE-600)2737824-X 2296634X nnns volume:9 year:2021 https://doi.org/10.3389/fcell.2021.705182 kostenfrei https://doaj.org/article/9d7d5542e32b4071b4aa9da8b86dd96c kostenfrei https://www.frontiersin.org/articles/10.3389/fcell.2021.705182/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 9 2021
allfieldsGer	10.3389/fcell.2021.705182 doi (DE-627)DOAJ019762267 (DE-599)DOAJ9d7d5542e32b4071b4aa9da8b86dd96c DE-627 ger DE-627 rakwb eng QH301-705.5 Melissa R. Bentley-Ford verfasserin aut ATXN10 Is Required for Embryonic Heart Development and Maintenance of Epithelial Cell Phenotypes in the Adult Kidney and Pancreas 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Atxn10 is a gene known for its role in cytokinesis and is associated with spinocerebellar ataxia (SCA10), a slowly progressing cerebellar syndrome caused by an intragenic pentanucleotide repeat expansion. Atxn10 is also implicated in the ciliopathy syndromes nephronophthisis (NPHP) and Joubert syndrome (JBTS), which are caused by the disruption of cilia function leading to nephron loss, impaired renal function, and cerebellar hypoplasia. How Atxn10 disruption contributes to these disorders remains unknown. Here, we generated Atxn10 congenital and conditional mutant mouse models. Our data indicate that while ATXN10 protein can be detected around the base of the cilium as well as in the cytosol, its loss does not cause overt changes in cilia formation or morphology. Congenital loss of Atxn10 results in embryonic lethality around E10.5 associated with pericardial effusion and loss of trabeculation. Similarly, tissue-specific loss of ATXN10 in the developing endothelium (Tie2-Cre) and myocardium (cTnT-Cre) also results in embryonic lethality with severe cardiac malformations occurring in the latter. Using an inducible Cagg-CreER to disrupt ATXN10 systemically at postnatal stages, we show that ATXN10 is also required for survival in adult mice. Loss of ATXN10 results in severe pancreatic and renal abnormalities leading to lethality within a few weeks post ATXN10 deletion in adult mice. Evaluation of these phenotypes further identified rapid epithelial-to-mesenchymal transition (EMT) in these tissues. In the pancreas, the phenotype includes signs of both acinar to ductal metaplasia and EMT with aberrant cilia formation and severe defects in glucose homeostasis related to pancreatic insufficiency or defects in feeding or nutrient intake. Collectively, this study identifies ATXN10 as an essential protein for survival. ataxin 10 (ATXN10) epithelial-to-mesenchymal transition (EMT) cilia acinar-to-ductal metaplasia (ADM) heart kidney Biology (General) Reagan S. Andersen verfasserin aut Mandy J. Croyle verfasserin aut Courtney J. Haycraft verfasserin aut Kelsey R. Clearman verfasserin aut Jeremy B. Foote verfasserin aut Jeremy F. Reiter verfasserin aut Jeremy F. Reiter verfasserin aut Bradley K. Yoder verfasserin aut In Frontiers in Cell and Developmental Biology Frontiers Media S.A., 2014 9(2021) (DE-627)770398138 (DE-600)2737824-X 2296634X nnns volume:9 year:2021 https://doi.org/10.3389/fcell.2021.705182 kostenfrei https://doaj.org/article/9d7d5542e32b4071b4aa9da8b86dd96c kostenfrei https://www.frontiersin.org/articles/10.3389/fcell.2021.705182/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 9 2021
allfieldsSound	10.3389/fcell.2021.705182 doi (DE-627)DOAJ019762267 (DE-599)DOAJ9d7d5542e32b4071b4aa9da8b86dd96c DE-627 ger DE-627 rakwb eng QH301-705.5 Melissa R. Bentley-Ford verfasserin aut ATXN10 Is Required for Embryonic Heart Development and Maintenance of Epithelial Cell Phenotypes in the Adult Kidney and Pancreas 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Atxn10 is a gene known for its role in cytokinesis and is associated with spinocerebellar ataxia (SCA10), a slowly progressing cerebellar syndrome caused by an intragenic pentanucleotide repeat expansion. Atxn10 is also implicated in the ciliopathy syndromes nephronophthisis (NPHP) and Joubert syndrome (JBTS), which are caused by the disruption of cilia function leading to nephron loss, impaired renal function, and cerebellar hypoplasia. How Atxn10 disruption contributes to these disorders remains unknown. Here, we generated Atxn10 congenital and conditional mutant mouse models. Our data indicate that while ATXN10 protein can be detected around the base of the cilium as well as in the cytosol, its loss does not cause overt changes in cilia formation or morphology. Congenital loss of Atxn10 results in embryonic lethality around E10.5 associated with pericardial effusion and loss of trabeculation. Similarly, tissue-specific loss of ATXN10 in the developing endothelium (Tie2-Cre) and myocardium (cTnT-Cre) also results in embryonic lethality with severe cardiac malformations occurring in the latter. Using an inducible Cagg-CreER to disrupt ATXN10 systemically at postnatal stages, we show that ATXN10 is also required for survival in adult mice. Loss of ATXN10 results in severe pancreatic and renal abnormalities leading to lethality within a few weeks post ATXN10 deletion in adult mice. Evaluation of these phenotypes further identified rapid epithelial-to-mesenchymal transition (EMT) in these tissues. In the pancreas, the phenotype includes signs of both acinar to ductal metaplasia and EMT with aberrant cilia formation and severe defects in glucose homeostasis related to pancreatic insufficiency or defects in feeding or nutrient intake. Collectively, this study identifies ATXN10 as an essential protein for survival. ataxin 10 (ATXN10) epithelial-to-mesenchymal transition (EMT) cilia acinar-to-ductal metaplasia (ADM) heart kidney Biology (General) Reagan S. Andersen verfasserin aut Mandy J. Croyle verfasserin aut Courtney J. Haycraft verfasserin aut Kelsey R. Clearman verfasserin aut Jeremy B. Foote verfasserin aut Jeremy F. Reiter verfasserin aut Jeremy F. Reiter verfasserin aut Bradley K. Yoder verfasserin aut In Frontiers in Cell and Developmental Biology Frontiers Media S.A., 2014 9(2021) (DE-627)770398138 (DE-600)2737824-X 2296634X nnns volume:9 year:2021 https://doi.org/10.3389/fcell.2021.705182 kostenfrei https://doaj.org/article/9d7d5542e32b4071b4aa9da8b86dd96c kostenfrei https://www.frontiersin.org/articles/10.3389/fcell.2021.705182/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 9 2021
language	English
source	In Frontiers in Cell and Developmental Biology 9(2021) volume:9 year:2021
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institution	findex.gbv.de
topic_facet	ataxin 10 (ATXN10) epithelial-to-mesenchymal transition (EMT) cilia acinar-to-ductal metaplasia (ADM) heart kidney Biology (General)
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container_title	Frontiers in Cell and Developmental Biology
authorswithroles_txt_mv	Melissa R. Bentley-Ford @@aut@@ Reagan S. Andersen @@aut@@ Mandy J. Croyle @@aut@@ Courtney J. Haycraft @@aut@@ Kelsey R. Clearman @@aut@@ Jeremy B. Foote @@aut@@ Jeremy F. Reiter @@aut@@ Bradley K. Yoder @@aut@@
publishDateDaySort_date	2021-01-01T00:00:00Z
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author	Melissa R. Bentley-Ford
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issn	2296634X
topic_title	QH301-705.5 ATXN10 Is Required for Embryonic Heart Development and Maintenance of Epithelial Cell Phenotypes in the Adult Kidney and Pancreas ataxin 10 (ATXN10) epithelial-to-mesenchymal transition (EMT) cilia acinar-to-ductal metaplasia (ADM) heart kidney
topic	misc QH301-705.5 misc ataxin 10 (ATXN10) misc epithelial-to-mesenchymal transition (EMT) misc cilia misc acinar-to-ductal metaplasia (ADM) misc heart misc kidney misc Biology (General)
topic_unstemmed	misc QH301-705.5 misc ataxin 10 (ATXN10) misc epithelial-to-mesenchymal transition (EMT) misc cilia misc acinar-to-ductal metaplasia (ADM) misc heart misc kidney misc Biology (General)
topic_browse	misc QH301-705.5 misc ataxin 10 (ATXN10) misc epithelial-to-mesenchymal transition (EMT) misc cilia misc acinar-to-ductal metaplasia (ADM) misc heart misc kidney misc Biology (General)
format_facet	Elektronische Aufsätze Aufsätze Elektronische Ressource
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title	ATXN10 Is Required for Embryonic Heart Development and Maintenance of Epithelial Cell Phenotypes in the Adult Kidney and Pancreas
ctrlnum	(DE-627)DOAJ019762267 (DE-599)DOAJ9d7d5542e32b4071b4aa9da8b86dd96c
title_full	ATXN10 Is Required for Embryonic Heart Development and Maintenance of Epithelial Cell Phenotypes in the Adult Kidney and Pancreas
author_sort	Melissa R. Bentley-Ford
journal	Frontiers in Cell and Developmental Biology
journalStr	Frontiers in Cell and Developmental Biology
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author_browse	Melissa R. Bentley-Ford Reagan S. Andersen Mandy J. Croyle Courtney J. Haycraft Kelsey R. Clearman Jeremy B. Foote Jeremy F. Reiter Bradley K. Yoder
container_volume	9
class	QH301-705.5
format_se	Elektronische Aufsätze
author-letter	Melissa R. Bentley-Ford
doi_str_mv	10.3389/fcell.2021.705182
author2-role	verfasserin
title_sort	atxn10 is required for embryonic heart development and maintenance of epithelial cell phenotypes in the adult kidney and pancreas
callnumber	QH301-705.5
title_auth	ATXN10 Is Required for Embryonic Heart Development and Maintenance of Epithelial Cell Phenotypes in the Adult Kidney and Pancreas
abstract	Atxn10 is a gene known for its role in cytokinesis and is associated with spinocerebellar ataxia (SCA10), a slowly progressing cerebellar syndrome caused by an intragenic pentanucleotide repeat expansion. Atxn10 is also implicated in the ciliopathy syndromes nephronophthisis (NPHP) and Joubert syndrome (JBTS), which are caused by the disruption of cilia function leading to nephron loss, impaired renal function, and cerebellar hypoplasia. How Atxn10 disruption contributes to these disorders remains unknown. Here, we generated Atxn10 congenital and conditional mutant mouse models. Our data indicate that while ATXN10 protein can be detected around the base of the cilium as well as in the cytosol, its loss does not cause overt changes in cilia formation or morphology. Congenital loss of Atxn10 results in embryonic lethality around E10.5 associated with pericardial effusion and loss of trabeculation. Similarly, tissue-specific loss of ATXN10 in the developing endothelium (Tie2-Cre) and myocardium (cTnT-Cre) also results in embryonic lethality with severe cardiac malformations occurring in the latter. Using an inducible Cagg-CreER to disrupt ATXN10 systemically at postnatal stages, we show that ATXN10 is also required for survival in adult mice. Loss of ATXN10 results in severe pancreatic and renal abnormalities leading to lethality within a few weeks post ATXN10 deletion in adult mice. Evaluation of these phenotypes further identified rapid epithelial-to-mesenchymal transition (EMT) in these tissues. In the pancreas, the phenotype includes signs of both acinar to ductal metaplasia and EMT with aberrant cilia formation and severe defects in glucose homeostasis related to pancreatic insufficiency or defects in feeding or nutrient intake. Collectively, this study identifies ATXN10 as an essential protein for survival.
abstractGer	Atxn10 is a gene known for its role in cytokinesis and is associated with spinocerebellar ataxia (SCA10), a slowly progressing cerebellar syndrome caused by an intragenic pentanucleotide repeat expansion. Atxn10 is also implicated in the ciliopathy syndromes nephronophthisis (NPHP) and Joubert syndrome (JBTS), which are caused by the disruption of cilia function leading to nephron loss, impaired renal function, and cerebellar hypoplasia. How Atxn10 disruption contributes to these disorders remains unknown. Here, we generated Atxn10 congenital and conditional mutant mouse models. Our data indicate that while ATXN10 protein can be detected around the base of the cilium as well as in the cytosol, its loss does not cause overt changes in cilia formation or morphology. Congenital loss of Atxn10 results in embryonic lethality around E10.5 associated with pericardial effusion and loss of trabeculation. Similarly, tissue-specific loss of ATXN10 in the developing endothelium (Tie2-Cre) and myocardium (cTnT-Cre) also results in embryonic lethality with severe cardiac malformations occurring in the latter. Using an inducible Cagg-CreER to disrupt ATXN10 systemically at postnatal stages, we show that ATXN10 is also required for survival in adult mice. Loss of ATXN10 results in severe pancreatic and renal abnormalities leading to lethality within a few weeks post ATXN10 deletion in adult mice. Evaluation of these phenotypes further identified rapid epithelial-to-mesenchymal transition (EMT) in these tissues. In the pancreas, the phenotype includes signs of both acinar to ductal metaplasia and EMT with aberrant cilia formation and severe defects in glucose homeostasis related to pancreatic insufficiency or defects in feeding or nutrient intake. Collectively, this study identifies ATXN10 as an essential protein for survival.
abstract_unstemmed	Atxn10 is a gene known for its role in cytokinesis and is associated with spinocerebellar ataxia (SCA10), a slowly progressing cerebellar syndrome caused by an intragenic pentanucleotide repeat expansion. Atxn10 is also implicated in the ciliopathy syndromes nephronophthisis (NPHP) and Joubert syndrome (JBTS), which are caused by the disruption of cilia function leading to nephron loss, impaired renal function, and cerebellar hypoplasia. How Atxn10 disruption contributes to these disorders remains unknown. Here, we generated Atxn10 congenital and conditional mutant mouse models. Our data indicate that while ATXN10 protein can be detected around the base of the cilium as well as in the cytosol, its loss does not cause overt changes in cilia formation or morphology. Congenital loss of Atxn10 results in embryonic lethality around E10.5 associated with pericardial effusion and loss of trabeculation. Similarly, tissue-specific loss of ATXN10 in the developing endothelium (Tie2-Cre) and myocardium (cTnT-Cre) also results in embryonic lethality with severe cardiac malformations occurring in the latter. Using an inducible Cagg-CreER to disrupt ATXN10 systemically at postnatal stages, we show that ATXN10 is also required for survival in adult mice. Loss of ATXN10 results in severe pancreatic and renal abnormalities leading to lethality within a few weeks post ATXN10 deletion in adult mice. Evaluation of these phenotypes further identified rapid epithelial-to-mesenchymal transition (EMT) in these tissues. In the pancreas, the phenotype includes signs of both acinar to ductal metaplasia and EMT with aberrant cilia formation and severe defects in glucose homeostasis related to pancreatic insufficiency or defects in feeding or nutrient intake. Collectively, this study identifies ATXN10 as an essential protein for survival.
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title_short	ATXN10 Is Required for Embryonic Heart Development and Maintenance of Epithelial Cell Phenotypes in the Adult Kidney and Pancreas
url	https://doi.org/10.3389/fcell.2021.705182 https://doaj.org/article/9d7d5542e32b4071b4aa9da8b86dd96c https://www.frontiersin.org/articles/10.3389/fcell.2021.705182/full https://doaj.org/toc/2296-634X
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author2	Reagan S. Andersen Mandy J. Croyle Courtney J. Haycraft Kelsey R. Clearman Jeremy B. Foote Jeremy F. Reiter Bradley K. Yoder
author2Str	Reagan S. Andersen Mandy J. Croyle Courtney J. Haycraft Kelsey R. Clearman Jeremy B. Foote Jeremy F. Reiter Bradley K. Yoder
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doi_str	10.3389/fcell.2021.705182
callnumber-a	QH301-705.5
up_date	2024-07-04T00:52:04.367Z
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