Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Neuronal cell fate specification by the molecular convergence of different spatio-temporal cues on a common initiator terminal selector gene
Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences.ORCID iD: 0000-0001-5095-541X
2017 (English)In: PLoS Genetics, ISSN 1553-7390, E-ISSN 1553-7404, Vol. 13, no 4, p. 26Article in journal (Refereed) Published
Abstract [en]

The extensive genetic regulatory flows underlying specification of different neuronal subtypes are not well understood at the molecular level. The Nplp1 neuropeptide neurons in the developing Drosophila nerve cord belong to two sub-classes; Tv1 and dAp neurons, generated by two distinct progenitors. Nplp1 neurons are specified by spatial cues; the Hox homeotic network and GATA factor grn, and temporal cues; the hb -greater than Kr -greater than Pdm -greater than cas -greater than grh temporal cascade. These spatio-temporal cues combine into two distinct codes; one for Tv1 and one for dAp neurons that activate a common terminal selector feedforward cascade of col -greater than ap/eya -greater than dimm -greater than Nplp1. Here, we molecularly decode the specification of Nplp1 neurons, and find that the cis-regulatory organization of col functions as an integratory node for the different spatio-temporal combinatorial codes. These findings may provide a logical framework for addressing spatio-temporal control of neuronal sub-type specification in other systems. [ABSTRACT FROM AUTHOR]

Place, publisher, year, edition, pages
PLOS , 2017. Vol. 13, no 4, p. 26
Keywords [en]
Animal cells, Animal models, Animals, Arthropoda, Biochemistry, Biology and life sciences, Cell binding, Cell biology, Cell physiology, Cell staining, Cellular neuroscience, Cellular types, Developmental biology, DNA-binding proteins, Drosophila, Drosophila melanogaster, Embryology, Embryos, Experimental organism systems, Gene expression, Gene regulation, Genetics, Insects, Invertebrates, Model organisms, Neurons, Neuroscience, Organisms, Proteins, Regulatory proteins, Research and analysis methods, Research Article, Specimen preparation and treatment, Staining, Transcription factors
National Category
Developmental Biology
Identifiers
URN: urn:nbn:se:liu:diva-136555DOI: 10.1371/journal.pgen.1006729ISI: 000402549200037PubMedID: 28414802OAI: oai:DiVA.org:liu-136555DiVA, id: diva2:1089452
Note

Funding agencies: Cancerfonden [140780]; Vetenskapsradet [621-20135258]; Knut och Alice Wallenbergs Stiftelse [KAW2011.0165]

Available from: 2017-04-19 Created: 2017-04-19 Last updated: 2017-06-26Bibliographically approved
In thesis
1. Genetic Mechanisms during Terminal Cell Fate Specification in the Drosophila CNS
Open this publication in new window or tab >>Genetic Mechanisms during Terminal Cell Fate Specification in the Drosophila CNS
2017 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Specification of the many unique neuronal subtypes found in the nervous system depends on spatiotemporal cues and terminal selector cascades, mostly acting in sequential combinatorial codes of transcription factors (TFs) to dictate cell fate. Out of 10,000 cells in the Drosophila embryonic ventral nerve cord (VNC), only 28 cells selectively express Nplp1. The Nplp1 neurons in the Drosophila VNC can be subdivided into the thoracic ventro-lateral Tv1 and the dorsal-medial dAp neurons. Nplp1 expression in both cell subtypes is activated by the same terminal selector cascade: col > ap/eya > dimm > Nplp1. However Tv1 and dAp neurons are generated by different neuronal progenitors (neuroblasts, NB), and depend on different upstream cues to activate the cell specification cascade. The Tv1 cells are generated by NB5-6T, and in these cells the Nplp1 terminal selector cascade is triggered by spatio-temporal input provided by Antp/hth/exd/lbe/cas. Our studies identified that NB4-3 gives rise to the dAp cells and that the Nplp1 terminal selector cascade in dAp cells is activated by Kr/pdm>grn. I demonstrated how two different spatio-temporal combinations can funnel on a shared downstream terminal selector cascade to determine a highly related cell fate, in different regions of the VNC. I tested this scenario at the molecular level, by identification of cisregulatory modules (CRMs) for the main factors involved in the Nplp1 terminal selector cascade. Intriguingly, I found that col is under control of two separate CRMs, which are controlled by either Antp/hth/exd/lbe/cas in the NB5-6T lineage, and Kr/pdm/grn in the NB4-3 lineage. In addition, CRISPR deletion of the endogenous col CRMs did not result in loss of Col and Nplp1, indicating that col might be under control of more, yet unidentified CRMs. Nplp1 is expressed in one out of four cells in the thoracic Apterous cluster (Ap cluster); the Tv1 cell. The allocation of the right cell fate to each of the four Ap cluster cells, is regulated by the sub-temporal cascade including the factors Sqz/Nab/Svp, acting downstream of the temporal factor Cas. The sub-temporal factors have a repressive action on Col and Dimm, and thus on the terminal selector cascade regulating Nplp1 expression in the Tv1  cell. We demonstrated that the late and Tv1 specific expression of the early temporal factor Kr suppresses Svp in the Tv1 cell and allows for the progression of the Nplp1 cell fate specification cascade. Hence, early temporal factors involved in temporal progression of neuronal progenitors, can be re-utilized late and postmitotically to specify cell fate. It is tempting to speculate that similar mechanisms act to generate similar cell fate in different regions of the CNS, as well as the issue of sub-temporal multitasking, are common features both in Drosophila and higher organisms.

Place, publisher, year, edition, pages
Linköping: Linköping University Electronic Press, 2017. p. 61
Series
Linköping University Medical Dissertations, ISSN 0345-0082 ; 1550
National Category
Cell Biology Neurosciences Cell and Molecular Biology
Identifiers
urn:nbn:se:liu:diva-133225 (URN)10.3384/diss.diva-133225 (DOI)9789176856475 (ISBN)
Public defence
2017-02-02, Berzeliussalen, Campus US, Linköping, 09:00 (Swedish)
Opponent
Supervisors
Available from: 2016-12-15 Created: 2016-12-15 Last updated: 2018-01-13Bibliographically approved

Open Access in DiVA

fulltext(14898 kB)42 downloads
File information
File name FULLTEXT01.pdfFile size 14898 kBChecksum SHA-512
bc040d2ac376be3ef3edb49a510671a5d0252acd13038aef93f1dc94c9de18b446f538ff5b80eb2ba95b673b24ef3f53f7330712b0d75df0d7939fd2d786de46
Type fulltextMimetype application/pdf

Other links

Publisher's full textPubMed

Search in DiVA

By author/editor
Stratmann, JohannesThor, Stefan
By organisation
Division of Microbiology and Molecular MedicineFaculty of Medicine and Health Sciences
In the same journal
PLoS Genetics
Developmental Biology

Search outside of DiVA

GoogleGoogle Scholar
Total: 42 downloads
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

doi
pubmed
urn-nbn

Altmetric score

doi
pubmed
urn-nbn
Total: 187 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf