Boolean modelling reveals new regulatory connections between transcription factors orchestrating the development of the ventral spinal cord
We have assembled a network of cell-fate determining transcription factors that play a key role in the specification of the ventral neuronal subtypes of the spinal cord on the basis of published transcriptional interactions. Asynchronous Boolean modelling of the network was used to compare simulation results with reported experimental observations. Such comparison highlighted the need to include additional regulatory connections in order to obtain the fixed point attractors of the model associated with the five known progenitor cell types located in the ventral spinal cord. The revised gene regulatory network reproduced previously observed cell state switches between progenitor cells observed in knock-out animal models or in experiments where the transcription factors were overexpressed. Furthermore the network predicted the inhibition of Irx3 by Nkx2.2 and this prediction was tested experimentally. Our results provide evidence for the existence of an as yet undescribed inhibitory connection which could potentially have significance beyond the ventral spinal cord. The work presented in this paper demonstrates the strength of Boolean modelling for identifying gene regulatory networks.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2014 |
|---|---|
| Erschienen: |
2014 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:9 |
|---|---|
| Enthalten in: |
PloS one - 9(2014), 11 vom: 05., Seite e111430 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Lovrics, Anna [VerfasserIn] |
|---|
| Links: |
|---|
| Themen: |
EC 1.13.12.- |
|---|
| Anmerkungen: |
Date Completed 14.07.2015 Date Revised 03.12.2021 published: Electronic-eCollection Citation Status MEDLINE |
|---|
| doi: |
10.1371/journal.pone.0111430 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM243547056 |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM243547056 | ||
| 003 | DE-627 | ||
| 005 | 20231224132746.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231224s2014 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1371/journal.pone.0111430 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n0811.xml |
| 035 | |a (DE-627)NLM243547056 | ||
| 035 | |a (NLM)25398016 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Lovrics, Anna |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Boolean modelling reveals new regulatory connections between transcription factors orchestrating the development of the ventral spinal cord |
| 264 | 1 | |c 2014 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 14.07.2015 | ||
| 500 | |a Date Revised 03.12.2021 | ||
| 500 | |a published: Electronic-eCollection | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a We have assembled a network of cell-fate determining transcription factors that play a key role in the specification of the ventral neuronal subtypes of the spinal cord on the basis of published transcriptional interactions. Asynchronous Boolean modelling of the network was used to compare simulation results with reported experimental observations. Such comparison highlighted the need to include additional regulatory connections in order to obtain the fixed point attractors of the model associated with the five known progenitor cell types located in the ventral spinal cord. The revised gene regulatory network reproduced previously observed cell state switches between progenitor cells observed in knock-out animal models or in experiments where the transcription factors were overexpressed. Furthermore the network predicted the inhibition of Irx3 by Nkx2.2 and this prediction was tested experimentally. Our results provide evidence for the existence of an as yet undescribed inhibitory connection which could potentially have significance beyond the ventral spinal cord. The work presented in this paper demonstrates the strength of Boolean modelling for identifying gene regulatory networks | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 7 | |a Homeobox Protein Nkx-2.2 |2 NLM | |
| 650 | 7 | |a Homeodomain Proteins |2 NLM | |
| 650 | 7 | |a NKX2-2 protein, human |2 NLM | |
| 650 | 7 | |a Nuclear Proteins |2 NLM | |
| 650 | 7 | |a Transcription Factors |2 NLM | |
| 650 | 7 | |a Luciferases |2 NLM | |
| 650 | 7 | |a EC 1.13.12.- |2 NLM | |
| 700 | 1 | |a Gao, Yu |e verfasserin |4 aut | |
| 700 | 1 | |a Juhász, Bianka |e verfasserin |4 aut | |
| 700 | 1 | |a Bock, István |e verfasserin |4 aut | |
| 700 | 1 | |a Byrne, Helen M |e verfasserin |4 aut | |
| 700 | 1 | |a Dinnyés, András |e verfasserin |4 aut | |
| 700 | 1 | |a Kovács, Krisztián A |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t PloS one |d 2006 |g 9(2014), 11 vom: 05., Seite e111430 |w (DE-627)NLM167327399 |x 1932-6203 |7 nnns |
| 773 | 1 | 8 | |g volume:9 |g year:2014 |g number:11 |g day:05 |g pages:e111430 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1371/journal.pone.0111430 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 9 |j 2014 |e 11 |b 05 |h e111430 | ||