Sharpening of expression domains induced by transcription and microRNA regulationwithin a spatio-temporal model of mid-hindbrain boundary formation
Background The establishment of the mid-hindbrain region in vertebrates is mediated by theisthmic organizer, an embryonic secondary organizer characterized by awell-defined pattern of locally restricted gene expression domains with sharplydelimited boundaries. While the function of the isthmic organ...
Ausführliche Beschreibung
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| Autor*in: |
Hock, Sabrina [verfasserIn] |
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| Format: |
E-Artikel |
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| Sprache: |
Englisch |
| Erschienen: |
2013 |
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| Anmerkung: |
© Hock et al.; licensee BioMed Central Ltd. 2013. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative CommonsAttribution License ( |
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| Übergeordnetes Werk: |
Enthalten in: BMC systems biology - London : BioMed Central, 2007, 7(2013), 1 vom: 25. Juni |
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| Übergeordnetes Werk: |
volume:7 ; year:2013 ; number:1 ; day:25 ; month:06 |
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| DOI / URN: |
10.1186/1752-0509-7-48 |
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| Katalog-ID: |
SPR028415310 |
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| 520 | |a Background The establishment of the mid-hindbrain region in vertebrates is mediated by theisthmic organizer, an embryonic secondary organizer characterized by awell-defined pattern of locally restricted gene expression domains with sharplydelimited boundaries. While the function of the isthmic organizer at themid-hindbrain boundary has been subject to extensive experimental studies, itremains unclear how this well-defined spatial gene expression pattern, which isessential for proper isthmic organizer function, is established during vertebratedevelopment. Because the secreted Wnt1 protein plays a prominent role in isthmicorganizer function, we focused in particular on the refinement of Wnt1gene expression in this context. Results We analyzed the dynamics of the corresponding murine gene regulatory network andthe related, diffusive signaling proteins using a macroscopic model for thebiological two-scale signaling process. Despite the discontinuity arisingfrom the sharp gene expression domain boundaries, we proved the existence ofunique, positive solutions for the partial differential equation system. Thisenabled the numerically and analytically analysis of the formation and stabilityof the expression pattern. Notably, the calculated expression domain ofWnt1 has no sharp boundary in contrast to experimental evidence. Wesubsequently propose a post-transcriptional regulatory mechanism for Wnt1miRNAs which yields the observed sharp expression domain boundaries. Weestablished a list of candidate miRNAs and confirmed their expression pattern byradioactive in situ hybridization. The miRNA miR-709 was identified as apotential regulator of Wnt1 mRNA, which was validated by luciferasesensor assays. Conclusion In summary, our theoretical analysis of the gene expression pattern induction atthe mid-hindbrain boundary revealed the need to extend the model by an additionalWnt1 regulation. The developed macroscopic model of a two-scaleprocess facilitate the stringent analysis of other morphogen-based patterningprocesses. | ||
| 650 | 4 | |a Mid-Hindbrain Boundary |7 (dpeaa)DE-He213 | |
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| 700 | 1 | |a Hasenauer, Jan |4 aut | |
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| 700 | 1 | |a Prakash, Nilima |4 aut | |
| 700 | 1 | |a Theis, Fabian J |4 aut | |
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10.1186/1752-0509-7-48 doi (DE-627)SPR028415310 (SPR)1752-0509-7-48-e DE-627 ger DE-627 rakwb eng Hock, Sabrina verfasserin aut Sharpening of expression domains induced by transcription and microRNA regulationwithin a spatio-temporal model of mid-hindbrain boundary formation 2013 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © Hock et al.; licensee BioMed Central Ltd. 2013. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative CommonsAttribution License ( Background The establishment of the mid-hindbrain region in vertebrates is mediated by theisthmic organizer, an embryonic secondary organizer characterized by awell-defined pattern of locally restricted gene expression domains with sharplydelimited boundaries. While the function of the isthmic organizer at themid-hindbrain boundary has been subject to extensive experimental studies, itremains unclear how this well-defined spatial gene expression pattern, which isessential for proper isthmic organizer function, is established during vertebratedevelopment. Because the secreted Wnt1 protein plays a prominent role in isthmicorganizer function, we focused in particular on the refinement of Wnt1gene expression in this context. Results We analyzed the dynamics of the corresponding murine gene regulatory network andthe related, diffusive signaling proteins using a macroscopic model for thebiological two-scale signaling process. Despite the discontinuity arisingfrom the sharp gene expression domain boundaries, we proved the existence ofunique, positive solutions for the partial differential equation system. Thisenabled the numerically and analytically analysis of the formation and stabilityof the expression pattern. Notably, the calculated expression domain ofWnt1 has no sharp boundary in contrast to experimental evidence. Wesubsequently propose a post-transcriptional regulatory mechanism for Wnt1miRNAs which yields the observed sharp expression domain boundaries. Weestablished a list of candidate miRNAs and confirmed their expression pattern byradioactive in situ hybridization. The miRNA miR-709 was identified as apotential regulator of Wnt1 mRNA, which was validated by luciferasesensor assays. Conclusion In summary, our theoretical analysis of the gene expression pattern induction atthe mid-hindbrain boundary revealed the need to extend the model by an additionalWnt1 regulation. The developed macroscopic model of a two-scaleprocess facilitate the stringent analysis of other morphogen-based patterningprocesses. Mid-Hindbrain Boundary (dpeaa)DE-He213 miRNA Modeling (dpeaa)DE-He213 Spatio-Temporal Model (dpeaa)DE-He213 Developemental Biology (dpeaa)DE-He213 Ng, Yen-Kar aut Hasenauer, Jan aut Wittmann, Dominik aut Lutter, Dominik aut Trümbach, Dietrich aut Wurst, Wolfgang aut Prakash, Nilima aut Theis, Fabian J aut Enthalten in BMC systems biology London : BioMed Central, 2007 7(2013), 1 vom: 25. Juni (DE-627)522897126 (DE-600)2265490-2 1752-0509 nnns volume:7 year:2013 number:1 day:25 month:06 https://dx.doi.org/10.1186/1752-0509-7-48 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 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_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 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 7 2013 1 25 06 |
| spelling |
10.1186/1752-0509-7-48 doi (DE-627)SPR028415310 (SPR)1752-0509-7-48-e DE-627 ger DE-627 rakwb eng Hock, Sabrina verfasserin aut Sharpening of expression domains induced by transcription and microRNA regulationwithin a spatio-temporal model of mid-hindbrain boundary formation 2013 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © Hock et al.; licensee BioMed Central Ltd. 2013. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative CommonsAttribution License ( Background The establishment of the mid-hindbrain region in vertebrates is mediated by theisthmic organizer, an embryonic secondary organizer characterized by awell-defined pattern of locally restricted gene expression domains with sharplydelimited boundaries. While the function of the isthmic organizer at themid-hindbrain boundary has been subject to extensive experimental studies, itremains unclear how this well-defined spatial gene expression pattern, which isessential for proper isthmic organizer function, is established during vertebratedevelopment. Because the secreted Wnt1 protein plays a prominent role in isthmicorganizer function, we focused in particular on the refinement of Wnt1gene expression in this context. Results We analyzed the dynamics of the corresponding murine gene regulatory network andthe related, diffusive signaling proteins using a macroscopic model for thebiological two-scale signaling process. Despite the discontinuity arisingfrom the sharp gene expression domain boundaries, we proved the existence ofunique, positive solutions for the partial differential equation system. Thisenabled the numerically and analytically analysis of the formation and stabilityof the expression pattern. Notably, the calculated expression domain ofWnt1 has no sharp boundary in contrast to experimental evidence. Wesubsequently propose a post-transcriptional regulatory mechanism for Wnt1miRNAs which yields the observed sharp expression domain boundaries. Weestablished a list of candidate miRNAs and confirmed their expression pattern byradioactive in situ hybridization. The miRNA miR-709 was identified as apotential regulator of Wnt1 mRNA, which was validated by luciferasesensor assays. Conclusion In summary, our theoretical analysis of the gene expression pattern induction atthe mid-hindbrain boundary revealed the need to extend the model by an additionalWnt1 regulation. The developed macroscopic model of a two-scaleprocess facilitate the stringent analysis of other morphogen-based patterningprocesses. Mid-Hindbrain Boundary (dpeaa)DE-He213 miRNA Modeling (dpeaa)DE-He213 Spatio-Temporal Model (dpeaa)DE-He213 Developemental Biology (dpeaa)DE-He213 Ng, Yen-Kar aut Hasenauer, Jan aut Wittmann, Dominik aut Lutter, Dominik aut Trümbach, Dietrich aut Wurst, Wolfgang aut Prakash, Nilima aut Theis, Fabian J aut Enthalten in BMC systems biology London : BioMed Central, 2007 7(2013), 1 vom: 25. Juni (DE-627)522897126 (DE-600)2265490-2 1752-0509 nnns volume:7 year:2013 number:1 day:25 month:06 https://dx.doi.org/10.1186/1752-0509-7-48 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 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_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 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 7 2013 1 25 06 |
| allfields_unstemmed |
10.1186/1752-0509-7-48 doi (DE-627)SPR028415310 (SPR)1752-0509-7-48-e DE-627 ger DE-627 rakwb eng Hock, Sabrina verfasserin aut Sharpening of expression domains induced by transcription and microRNA regulationwithin a spatio-temporal model of mid-hindbrain boundary formation 2013 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © Hock et al.; licensee BioMed Central Ltd. 2013. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative CommonsAttribution License ( Background The establishment of the mid-hindbrain region in vertebrates is mediated by theisthmic organizer, an embryonic secondary organizer characterized by awell-defined pattern of locally restricted gene expression domains with sharplydelimited boundaries. While the function of the isthmic organizer at themid-hindbrain boundary has been subject to extensive experimental studies, itremains unclear how this well-defined spatial gene expression pattern, which isessential for proper isthmic organizer function, is established during vertebratedevelopment. Because the secreted Wnt1 protein plays a prominent role in isthmicorganizer function, we focused in particular on the refinement of Wnt1gene expression in this context. Results We analyzed the dynamics of the corresponding murine gene regulatory network andthe related, diffusive signaling proteins using a macroscopic model for thebiological two-scale signaling process. Despite the discontinuity arisingfrom the sharp gene expression domain boundaries, we proved the existence ofunique, positive solutions for the partial differential equation system. Thisenabled the numerically and analytically analysis of the formation and stabilityof the expression pattern. Notably, the calculated expression domain ofWnt1 has no sharp boundary in contrast to experimental evidence. Wesubsequently propose a post-transcriptional regulatory mechanism for Wnt1miRNAs which yields the observed sharp expression domain boundaries. Weestablished a list of candidate miRNAs and confirmed their expression pattern byradioactive in situ hybridization. The miRNA miR-709 was identified as apotential regulator of Wnt1 mRNA, which was validated by luciferasesensor assays. Conclusion In summary, our theoretical analysis of the gene expression pattern induction atthe mid-hindbrain boundary revealed the need to extend the model by an additionalWnt1 regulation. The developed macroscopic model of a two-scaleprocess facilitate the stringent analysis of other morphogen-based patterningprocesses. Mid-Hindbrain Boundary (dpeaa)DE-He213 miRNA Modeling (dpeaa)DE-He213 Spatio-Temporal Model (dpeaa)DE-He213 Developemental Biology (dpeaa)DE-He213 Ng, Yen-Kar aut Hasenauer, Jan aut Wittmann, Dominik aut Lutter, Dominik aut Trümbach, Dietrich aut Wurst, Wolfgang aut Prakash, Nilima aut Theis, Fabian J aut Enthalten in BMC systems biology London : BioMed Central, 2007 7(2013), 1 vom: 25. Juni (DE-627)522897126 (DE-600)2265490-2 1752-0509 nnns volume:7 year:2013 number:1 day:25 month:06 https://dx.doi.org/10.1186/1752-0509-7-48 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 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_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 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 7 2013 1 25 06 |
| allfieldsGer |
10.1186/1752-0509-7-48 doi (DE-627)SPR028415310 (SPR)1752-0509-7-48-e DE-627 ger DE-627 rakwb eng Hock, Sabrina verfasserin aut Sharpening of expression domains induced by transcription and microRNA regulationwithin a spatio-temporal model of mid-hindbrain boundary formation 2013 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © Hock et al.; licensee BioMed Central Ltd. 2013. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative CommonsAttribution License ( Background The establishment of the mid-hindbrain region in vertebrates is mediated by theisthmic organizer, an embryonic secondary organizer characterized by awell-defined pattern of locally restricted gene expression domains with sharplydelimited boundaries. While the function of the isthmic organizer at themid-hindbrain boundary has been subject to extensive experimental studies, itremains unclear how this well-defined spatial gene expression pattern, which isessential for proper isthmic organizer function, is established during vertebratedevelopment. Because the secreted Wnt1 protein plays a prominent role in isthmicorganizer function, we focused in particular on the refinement of Wnt1gene expression in this context. Results We analyzed the dynamics of the corresponding murine gene regulatory network andthe related, diffusive signaling proteins using a macroscopic model for thebiological two-scale signaling process. Despite the discontinuity arisingfrom the sharp gene expression domain boundaries, we proved the existence ofunique, positive solutions for the partial differential equation system. Thisenabled the numerically and analytically analysis of the formation and stabilityof the expression pattern. Notably, the calculated expression domain ofWnt1 has no sharp boundary in contrast to experimental evidence. Wesubsequently propose a post-transcriptional regulatory mechanism for Wnt1miRNAs which yields the observed sharp expression domain boundaries. Weestablished a list of candidate miRNAs and confirmed their expression pattern byradioactive in situ hybridization. The miRNA miR-709 was identified as apotential regulator of Wnt1 mRNA, which was validated by luciferasesensor assays. Conclusion In summary, our theoretical analysis of the gene expression pattern induction atthe mid-hindbrain boundary revealed the need to extend the model by an additionalWnt1 regulation. The developed macroscopic model of a two-scaleprocess facilitate the stringent analysis of other morphogen-based patterningprocesses. Mid-Hindbrain Boundary (dpeaa)DE-He213 miRNA Modeling (dpeaa)DE-He213 Spatio-Temporal Model (dpeaa)DE-He213 Developemental Biology (dpeaa)DE-He213 Ng, Yen-Kar aut Hasenauer, Jan aut Wittmann, Dominik aut Lutter, Dominik aut Trümbach, Dietrich aut Wurst, Wolfgang aut Prakash, Nilima aut Theis, Fabian J aut Enthalten in BMC systems biology London : BioMed Central, 2007 7(2013), 1 vom: 25. Juni (DE-627)522897126 (DE-600)2265490-2 1752-0509 nnns volume:7 year:2013 number:1 day:25 month:06 https://dx.doi.org/10.1186/1752-0509-7-48 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 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_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 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 7 2013 1 25 06 |
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10.1186/1752-0509-7-48 doi (DE-627)SPR028415310 (SPR)1752-0509-7-48-e DE-627 ger DE-627 rakwb eng Hock, Sabrina verfasserin aut Sharpening of expression domains induced by transcription and microRNA regulationwithin a spatio-temporal model of mid-hindbrain boundary formation 2013 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © Hock et al.; licensee BioMed Central Ltd. 2013. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative CommonsAttribution License ( Background The establishment of the mid-hindbrain region in vertebrates is mediated by theisthmic organizer, an embryonic secondary organizer characterized by awell-defined pattern of locally restricted gene expression domains with sharplydelimited boundaries. While the function of the isthmic organizer at themid-hindbrain boundary has been subject to extensive experimental studies, itremains unclear how this well-defined spatial gene expression pattern, which isessential for proper isthmic organizer function, is established during vertebratedevelopment. Because the secreted Wnt1 protein plays a prominent role in isthmicorganizer function, we focused in particular on the refinement of Wnt1gene expression in this context. Results We analyzed the dynamics of the corresponding murine gene regulatory network andthe related, diffusive signaling proteins using a macroscopic model for thebiological two-scale signaling process. Despite the discontinuity arisingfrom the sharp gene expression domain boundaries, we proved the existence ofunique, positive solutions for the partial differential equation system. Thisenabled the numerically and analytically analysis of the formation and stabilityof the expression pattern. Notably, the calculated expression domain ofWnt1 has no sharp boundary in contrast to experimental evidence. Wesubsequently propose a post-transcriptional regulatory mechanism for Wnt1miRNAs which yields the observed sharp expression domain boundaries. Weestablished a list of candidate miRNAs and confirmed their expression pattern byradioactive in situ hybridization. The miRNA miR-709 was identified as apotential regulator of Wnt1 mRNA, which was validated by luciferasesensor assays. Conclusion In summary, our theoretical analysis of the gene expression pattern induction atthe mid-hindbrain boundary revealed the need to extend the model by an additionalWnt1 regulation. The developed macroscopic model of a two-scaleprocess facilitate the stringent analysis of other morphogen-based patterningprocesses. Mid-Hindbrain Boundary (dpeaa)DE-He213 miRNA Modeling (dpeaa)DE-He213 Spatio-Temporal Model (dpeaa)DE-He213 Developemental Biology (dpeaa)DE-He213 Ng, Yen-Kar aut Hasenauer, Jan aut Wittmann, Dominik aut Lutter, Dominik aut Trümbach, Dietrich aut Wurst, Wolfgang aut Prakash, Nilima aut Theis, Fabian J aut Enthalten in BMC systems biology London : BioMed Central, 2007 7(2013), 1 vom: 25. Juni (DE-627)522897126 (DE-600)2265490-2 1752-0509 nnns volume:7 year:2013 number:1 day:25 month:06 https://dx.doi.org/10.1186/1752-0509-7-48 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 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_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 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 7 2013 1 25 06 |
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Sharpening of expression domains induced by transcription and microRNA regulationwithin a spatio-temporal model of mid-hindbrain boundary formation |
| abstract |
Background The establishment of the mid-hindbrain region in vertebrates is mediated by theisthmic organizer, an embryonic secondary organizer characterized by awell-defined pattern of locally restricted gene expression domains with sharplydelimited boundaries. While the function of the isthmic organizer at themid-hindbrain boundary has been subject to extensive experimental studies, itremains unclear how this well-defined spatial gene expression pattern, which isessential for proper isthmic organizer function, is established during vertebratedevelopment. Because the secreted Wnt1 protein plays a prominent role in isthmicorganizer function, we focused in particular on the refinement of Wnt1gene expression in this context. Results We analyzed the dynamics of the corresponding murine gene regulatory network andthe related, diffusive signaling proteins using a macroscopic model for thebiological two-scale signaling process. Despite the discontinuity arisingfrom the sharp gene expression domain boundaries, we proved the existence ofunique, positive solutions for the partial differential equation system. Thisenabled the numerically and analytically analysis of the formation and stabilityof the expression pattern. Notably, the calculated expression domain ofWnt1 has no sharp boundary in contrast to experimental evidence. Wesubsequently propose a post-transcriptional regulatory mechanism for Wnt1miRNAs which yields the observed sharp expression domain boundaries. Weestablished a list of candidate miRNAs and confirmed their expression pattern byradioactive in situ hybridization. The miRNA miR-709 was identified as apotential regulator of Wnt1 mRNA, which was validated by luciferasesensor assays. Conclusion In summary, our theoretical analysis of the gene expression pattern induction atthe mid-hindbrain boundary revealed the need to extend the model by an additionalWnt1 regulation. The developed macroscopic model of a two-scaleprocess facilitate the stringent analysis of other morphogen-based patterningprocesses. © Hock et al.; licensee BioMed Central Ltd. 2013. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative CommonsAttribution License ( |
| abstractGer |
Background The establishment of the mid-hindbrain region in vertebrates is mediated by theisthmic organizer, an embryonic secondary organizer characterized by awell-defined pattern of locally restricted gene expression domains with sharplydelimited boundaries. While the function of the isthmic organizer at themid-hindbrain boundary has been subject to extensive experimental studies, itremains unclear how this well-defined spatial gene expression pattern, which isessential for proper isthmic organizer function, is established during vertebratedevelopment. Because the secreted Wnt1 protein plays a prominent role in isthmicorganizer function, we focused in particular on the refinement of Wnt1gene expression in this context. Results We analyzed the dynamics of the corresponding murine gene regulatory network andthe related, diffusive signaling proteins using a macroscopic model for thebiological two-scale signaling process. Despite the discontinuity arisingfrom the sharp gene expression domain boundaries, we proved the existence ofunique, positive solutions for the partial differential equation system. Thisenabled the numerically and analytically analysis of the formation and stabilityof the expression pattern. Notably, the calculated expression domain ofWnt1 has no sharp boundary in contrast to experimental evidence. Wesubsequently propose a post-transcriptional regulatory mechanism for Wnt1miRNAs which yields the observed sharp expression domain boundaries. Weestablished a list of candidate miRNAs and confirmed their expression pattern byradioactive in situ hybridization. The miRNA miR-709 was identified as apotential regulator of Wnt1 mRNA, which was validated by luciferasesensor assays. Conclusion In summary, our theoretical analysis of the gene expression pattern induction atthe mid-hindbrain boundary revealed the need to extend the model by an additionalWnt1 regulation. The developed macroscopic model of a two-scaleprocess facilitate the stringent analysis of other morphogen-based patterningprocesses. © Hock et al.; licensee BioMed Central Ltd. 2013. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative CommonsAttribution License ( |
| abstract_unstemmed |
Background The establishment of the mid-hindbrain region in vertebrates is mediated by theisthmic organizer, an embryonic secondary organizer characterized by awell-defined pattern of locally restricted gene expression domains with sharplydelimited boundaries. While the function of the isthmic organizer at themid-hindbrain boundary has been subject to extensive experimental studies, itremains unclear how this well-defined spatial gene expression pattern, which isessential for proper isthmic organizer function, is established during vertebratedevelopment. Because the secreted Wnt1 protein plays a prominent role in isthmicorganizer function, we focused in particular on the refinement of Wnt1gene expression in this context. Results We analyzed the dynamics of the corresponding murine gene regulatory network andthe related, diffusive signaling proteins using a macroscopic model for thebiological two-scale signaling process. Despite the discontinuity arisingfrom the sharp gene expression domain boundaries, we proved the existence ofunique, positive solutions for the partial differential equation system. Thisenabled the numerically and analytically analysis of the formation and stabilityof the expression pattern. Notably, the calculated expression domain ofWnt1 has no sharp boundary in contrast to experimental evidence. Wesubsequently propose a post-transcriptional regulatory mechanism for Wnt1miRNAs which yields the observed sharp expression domain boundaries. Weestablished a list of candidate miRNAs and confirmed their expression pattern byradioactive in situ hybridization. The miRNA miR-709 was identified as apotential regulator of Wnt1 mRNA, which was validated by luciferasesensor assays. Conclusion In summary, our theoretical analysis of the gene expression pattern induction atthe mid-hindbrain boundary revealed the need to extend the model by an additionalWnt1 regulation. The developed macroscopic model of a two-scaleprocess facilitate the stringent analysis of other morphogen-based patterningprocesses. © Hock et al.; licensee BioMed Central Ltd. 2013. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative CommonsAttribution License ( |
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Sharpening of expression domains induced by transcription and microRNA regulationwithin a spatio-temporal model of mid-hindbrain boundary formation |
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https://dx.doi.org/10.1186/1752-0509-7-48 |
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Ng, Yen-Kar Hasenauer, Jan Wittmann, Dominik Lutter, Dominik Trümbach, Dietrich Wurst, Wolfgang Prakash, Nilima Theis, Fabian J |
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Ng, Yen-Kar Hasenauer, Jan Wittmann, Dominik Lutter, Dominik Trümbach, Dietrich Wurst, Wolfgang Prakash, Nilima Theis, Fabian J |
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