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Karlsson, Daniel
Publications (10 of 13) Show all publications
Baumgardt, M., Karlsson, D., Yaghmaeian Salmani, B., Bivik, C., MacDonald, R., Gunnar, E. & Thor, S. (2014). Global Programmed Switch in Neural Daughter Cell Proliferation Mode Triggered by a Temporal Gene Cascade. Developmental Cell, 30(2), 192-208
Open this publication in new window or tab >>Global Programmed Switch in Neural Daughter Cell Proliferation Mode Triggered by a Temporal Gene Cascade
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2014 (English)In: Developmental Cell, ISSN 1534-5807, E-ISSN 1878-1551, Vol. 30, no 2, p. 192-208Article in journal (Refereed) Published
Abstract [en]

During central nervous system (CNS) development, progenitors typically divide asymmetrically, renewing themselves while budding off daughter cells with more limited proliferative potential. Variation in daughter cell proliferation has a profound impact on CNS development and evolution, but the underlying mechanisms remain poorly understood. We find that Drosophila embryonic neural progenitors (neuroblasts) undergo a programmed daughter proliferation mode switch, from generating daughters that divide once (type I) to generating neurons directly (type 0). This typelgreater than0 switch is triggered by activation of Dacapo (mammalian p21(CIP1)/p27(KIP1)/p57(Kip2)) expression in neuroblasts. In the thoracic region, Dacapo expression is activated by the temporal cascade (castor) and the Hox gene Antennapedia. In addition, castor, Antennapedia, and the late temporal gene grainyhead act combinatorially to control the precise timing of neuroblast cell-cycle exit by repressing Cyclin E and E2f. This reveals a logical principle underlying progenitor and daughter cell proliferation control in the Drosophila CNS.

Place, publisher, year, edition, pages
Elsevier (Cell Press), 2014
National Category
Basic Medicine
Identifiers
urn:nbn:se:liu:diva-109588 (URN)10.1016/j.devcel.2014.06.021 (DOI)000339641500012 ()25073156 (PubMedID)
Available from: 2014-08-21 Created: 2014-08-21 Last updated: 2019-03-13
Ulvklo, C., MacDonald, R., Bivik, C., Baumgardt, M., Karlsson, D. & Thor, S. (2012). Control of neuronal cell fate and number by integration of distinct daughter cell proliferation modes with temporal progression. Development, 139(4), 678-689
Open this publication in new window or tab >>Control of neuronal cell fate and number by integration of distinct daughter cell proliferation modes with temporal progression
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2012 (English)In: Development, ISSN 0950-1991, E-ISSN 1477-9129, Vol. 139, no 4, p. 678-689Article in journal (Refereed) Published
Abstract [en]

During neural lineage progression, differences in daughter cell proliferation can generate different lineage topologies. This is apparent in the Drosophila neuroblast 5-6 lineage (NB5-6T), which undergoes a daughter cell proliferation switch from generating daughter cells that divide once to generating neurons directly. Simultaneously, neural lineages, e.g. NB5-6T, undergo temporal changes in competence, as evidenced by the generation of different neural subtypes at distinct time points. When daughter proliferation is altered against a backdrop of temporal competence changes, it may create an integrative mechanism for simultaneously controlling cell fate and number. Here, we identify two independent pathways, Prospero and Notch, which act in concert to control the different daughter cell proliferation modes in NB5-6T. Altering daughter cell proliferation and temporal progression, individually and simultaneously, results in predictable changes in cell fate and number. This demonstrates that different daughter cell proliferation modes can be integrated with temporal competence changes, and suggests a novel mechanism for coordinately controlling neuronal subtype numbers.

Place, publisher, year, edition, pages
Company of Biologists, 2012
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-74790 (URN)10.1242/dev.074500 (DOI)000300259800005 ()
Note

funding agencies|Swedish Research Council||Knut and Alice Wallenberg foundation||Swedish Cancer Foundation||

Available from: 2012-02-08 Created: 2012-02-08 Last updated: 2019-03-13
Merabet, S., Litim-Mecheri, I., Karlsson, D., Dixit, R., Saadaoui, M., Monier, B., . . . Graba, Y. (2011). Insights into Hox Protein Function from a Large Scale Combinatorial Analysis of Protein Domains. PLoS Genetics, 7(10)
Open this publication in new window or tab >>Insights into Hox Protein Function from a Large Scale Combinatorial Analysis of Protein Domains
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2011 (English)In: PLoS Genetics, ISSN 1553-7390, Vol. 7, no 10Article in journal (Refereed) Published
Abstract [en]

Protein function is encoded within protein sequence and protein domains. However, how protein domains cooperate within a protein to modulate overall activity and how this impacts functional diversification at the molecular and organism levels remains largely unaddressed. Focusing on three domains of the central class Drosophila Hox transcription factor AbdominalA (AbdA), we used combinatorial domain mutations and most known AbdA developmental functions as biological readouts to investigate how protein domains collectively shape protein activity. The results uncover redundancy, interactivity, and multifunctionality of protein domains as salient features underlying overall AbdA protein activity, providing means to apprehend functional diversity and accounting for the robustness of Hox-controlled developmental programs. Importantly, the results highlight context-dependency in protein domain usage and interaction, allowing major modifications in domains to be tolerated without general functional loss. The non-pleoitropic effect of domain mutation suggests that protein modification may contribute more broadly to molecular changes underlying morphological diversification during evolution, so far thought to rely largely on modification in gene cis-regulatory sequences.

Place, publisher, year, edition, pages
PLoS, 2011
National Category
Natural Sciences
Identifiers
urn:nbn:se:liu:diva-72180 (URN)10.1371/journal.pgen.1002302 (DOI)000296665400008 ()
Note
Funding agencies|CNRS||Universite de la Mediterranee||ANR||FRM||CEFIPRA||ARC||Swedish Research Council||Swedish Strategic Research Foundation||Knut and Alice Wallenberg Foundation||Swedish "Hjarnfonden," "Cancerfonden,"||Swedish Royal Academy of Sciences||Universite de la Mediterrannee||AFM||Available from: 2011-11-21 Created: 2011-11-21 Last updated: 2016-11-30
MacDonald, R., Ulvklo, C., Bivik, C., Baumgardt, M., Karlsson, D. & Thor, S. (2011). Notch Mediates a Genetic Switch in Neural Lineage Topology in DEVELOPMENTAL BIOLOGY, vol 356, issue 1, pp 227-227. In: DEVELOPMENTAL BIOLOGY: (pp. 227-227). Elsevier Science B.V., Amsterdam, 356(1)
Open this publication in new window or tab >>Notch Mediates a Genetic Switch in Neural Lineage Topology in DEVELOPMENTAL BIOLOGY, vol 356, issue 1, pp 227-227
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2011 (English)In: DEVELOPMENTAL BIOLOGY, Elsevier Science B.V., Amsterdam , 2011, Vol. 356, no 1, p. 227-227Conference paper, Published paper (Refereed)
Abstract [en]

n/a

Place, publisher, year, edition, pages
Elsevier Science B.V., Amsterdam, 2011
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-69781 (URN)10.1016/j.ydbio.2011.05.375 (DOI)000292784400400 ()
Available from: 2011-08-10 Created: 2011-08-08 Last updated: 2019-03-13
Thor, S., Baumgardt, M. & Karlsson, D. (2010). From progenitor to unique neuron Neuronal sub-type specification by the integration of positional and temporal cues in INTERNATIONAL JOURNAL OF DEVELOPMENTAL NEUROSCIENCE, vol 28, issue 8, pp 671-671. In: INTERNATIONAL JOURNAL OF DEVELOPMENTAL NEUROSCIENCE (pp. 671-671). Elsevier Science B.V., Amsterdam., 28(8)
Open this publication in new window or tab >>From progenitor to unique neuron Neuronal sub-type specification by the integration of positional and temporal cues in INTERNATIONAL JOURNAL OF DEVELOPMENTAL NEUROSCIENCE, vol 28, issue 8, pp 671-671
2010 (English)In: INTERNATIONAL JOURNAL OF DEVELOPMENTAL NEUROSCIENCE, Elsevier Science B.V., Amsterdam. , 2010, Vol. 28, no 8, p. 671-671Conference paper, Published paper (Refereed)
Abstract [en]

n/a

Place, publisher, year, edition, pages
Elsevier Science B.V., Amsterdam., 2010
Keywords
Cell specification, Neuronal sub-types, Progenitor identity, Positional and temporal cues
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-64765 (URN)10.1016/j.ijdevneu.2010.07.088 (DOI)000284967600085 ()
Available from: 2011-02-04 Created: 2011-02-04 Last updated: 2016-11-30
Karlsson, D., Baumgardt, M. & Thor, S. (2010). Segment-specific Neuronal Sub-type Specification by the Integration of Anteroposterior and Temporal Cues. PLoS biology, 8(5)
Open this publication in new window or tab >>Segment-specific Neuronal Sub-type Specification by the Integration of Anteroposterior and Temporal Cues
2010 (English)In: PLoS biology, ISSN 1544-9173, E-ISSN 1545-7885, Vol. 8, no 5Article in journal (Refereed) Published
Abstract [en]

The generation of distinct neuronal sub-types at different axial levels relies upon both anteroposterior and temporal cues. However, the integration between these cues is poorly understood. In the Drosophila CNS, the segmentally repeated neuroblast 5-6 generates a unique group of neurons, the Apterous cluster, only in thoracic segments. Recent studies have identified elaborate genetic pathways acting to control the generation of these neurons. These insights, combined with novel markers, provide a unique opportunity for addressing how anteroposterior and temporal cues are integrated to generate segment-specific neuronal sub-types. We find that Pbx/Meis, Hox and temporal genes act in three different ways. Posteriorly, Pbx/Meis and posterior Hox genes block lineage progression within an early temporal window, by triggering cell cycle exit. Because Ap neurons are generated late in the thoracic 5-6 lineage, this prevents generation of Ap cluster cells in the abdomen. Thoracically, Pbx/Meis and anterior Hox genes integrate with late temporal genes to specify Ap clusters, via activation of a specific feed-forward loop. In brain segments, ‘Ap cluster cells’ are present but lack both proper Hox and temporal coding. Only by simultaneously altering Hox and temporal gene activity in all segments can Ap clusters be generated throughout the neuroaxis. This study provides the first detailed analysis of an identified neuroblast lineage along the entire neuroaxis, and provides novel insight into how Hox/Pbx/Meis anteroposterior cues are integrated with temporal cues. It reveals a surprisingly restricted yet multifaceted function of the anteroposterior cues with respect to lineage control and cell fate specification.

Keywords
anteroposterior patterning, temporal transitions, Hox, Pbx/Meis, cell specification
National Category
Developmental Biology
Identifiers
urn:nbn:se:liu:diva-51641 (URN)10.1371/journal.pbio.1000368 (DOI)000278759600005 ()
Note
Original Publication: Daniel Karlsson, Magnus Baumgardt and Stefan Thor, Segment-specific Neuronal Sub-type Specification by the Integration of Anteroposterior and Temporal Cues, 2010, PLoS biology, (8), 5. http://dx.doi.org/10.1371/journal.pbio.1000368 Licensee: Public Library of Science http://www.plos.org/ Available from: 2009-11-11 Created: 2009-11-11 Last updated: 2017-12-12Bibliographically approved
Karlsson, D. (2010). Specification of unique neuronal sub-types by integration of positional and temporal cues. (Doctoral dissertation). Linköping: Linköping University Electronic Press
Open this publication in new window or tab >>Specification of unique neuronal sub-types by integration of positional and temporal cues
2010 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

The nervous system contains vast numbers of neuronal sub-types, generated at specific time points, in the proper location, and in proper numbers. One of the fundamental issues in neurobiology is to understand the molecular genetic mechanisms that underlie the generation of this daunting neuronal diversity.

To help shed light upon these fundamental questions, my PhD project has addressed the generation and specification of a certain group of neurons, the Ap cluster. This group of four neurons is found only in thoracic segments within the Drosophila melanogaster central nervous system, and consists of three different cell types. Mapping of the neuroblast (stem cell) that generates the Ap cluster neurons, neuroblast 5-6, and the highly restricted appearance of this cluster allowed me to address the following questions: How does NB 5-6 change its temporal competence over time to generate the Ap cluster neurons late in the lineage, and how is temporal competence altered to ensure diversity among the Ap neurons? What are the mechanisms that allow these Ap cluster neurons to emerge only in the thoracic segments?

My studies have helped identify a number of mechanisms acting to specify the Ap cluster neurons. One type of mechanism involves several of different feed-forward loops that play out during NB 5-6 lineage development. These are triggered within the stem cell, where the temporal gene castor activates a number of genes. These castor targets are subsequently involved in several regulatory feed-forward loops, that ultimately result in the unique combinatorial expression of cell fate determinants in the different Ap neurons, which in turn ultimately lead to the activation of unique terminal differentiation genes. In addition, I have identified three different mechanisms by which the NB 5-6 lineage is modulated along the neuroaxis. In the abdomen I find that an early cell cycle exit is initiated by the Bx-C gene members and Pbx/Meis cofactors, which result in the truncation of the NB 5-6 lineage, preventing the Ap cluster neurons from being generated. In thoracic segments Hox, Pbx/Meisand temporal genes act in concert to specify Ap cluster neurons, by integrating with the castor temporal gene. In anterior segments, improper Hox and temporal coding results in a failure to specify bona fide Ap cluster neurons, even though equivalents of Ap cluster neurons are generated.

In summary, my thesis work has helped identify a number of mechanisms acting to specify this unique neuronal sub-type, including: feed-forward combinatorial coding, opposing feed-forward loops and integrated temporal/Hox mediated specification throughout different axial levels. I suggest that these mechanisms may be widely used within the animal kingdom, hence contributing to the great cellular diversity observed within the central nervous system of most animal species.

Place, publisher, year, edition, pages
Linköping: Linköping University Electronic Press, 2010. p. 102
Series
Linköping University Medical Dissertations, ISSN 0345-0082 ; 1211
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-63628 (URN)978-91-7393-306-3 (ISBN)
Public defence
2010-12-03, Linden, Universitetssjukhuset, Campus US, Linköpings universitet, Linköping, 09:00 (English)
Opponent
Supervisors
Available from: 2010-12-28 Created: 2010-12-28 Last updated: 2016-11-30Bibliographically approved
Baumgardt, M., Karlsson, D., Terriente, J., J Diaz-Benjumea, F. & Thor , S. (2009). From stem cell to unique neuron: Temporal transitions in an identified CNS progenitor cell by feedforward combinatorial coding. In: The 12th European Drosophila Neurobiology Conference 6-10 September 2008 Wuerzburg, Germany: in: Journal of Neurogenetics, Volume 23 Supplement 1 2009 (pp. S14-S15). , 23
Open this publication in new window or tab >>From stem cell to unique neuron: Temporal transitions in an identified CNS progenitor cell by feedforward combinatorial coding
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2009 (English)In: The 12th European Drosophila Neurobiology Conference 6-10 September 2008 Wuerzburg, Germany: in: Journal of Neurogenetics, Volume 23 Supplement 1 2009, 2009, Vol. 23, p. S14-S15Conference paper, Published paper (Refereed)
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-17149 (URN)
Available from: 2009-03-07 Created: 2009-03-07 Last updated: 2016-11-30
Baumgardt, M., Karlsson, D., Terriente, J., Díaz-Benjumea, F. J. & Thor, S. (2009). Neuronal Subtype Specification within a Lineage by Opposing Temporal Feed-Forward Loops. Cell, 139(5), 969-982
Open this publication in new window or tab >>Neuronal Subtype Specification within a Lineage by Opposing Temporal Feed-Forward Loops
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2009 (English)In: Cell, ISSN 0092-8674, E-ISSN 1097-4172, Vol. 139, no 5, p. 969-982Article in journal (Refereed) Published
Abstract [en]

Neural progenitors generate distinct cell types at different stages, but the mechanisms controlling these temporal transitions are poorly understood. In the Drosophila CNS, a cascade of transcription factors, the ‘temporal gene cascade’, has been identified, that acts to alter progenitor competence over time. However, many CNS lineages display broad temporal windows, and it is unclear how broad windows progress into sub-windows that generate unique cell types. We have addressed this issue in an identifiable Drosophila CNS lineage, and find that a broad castor temporal window is sub-divided by two different feed-forward loops, both of which are triggered by castor itself. The first loop acts to specify a unique cell fate, while the second loop suppresses the first loop, thereby allowing for the generation of alternate cell fates. This mechanism of temporal and ‘sub-temporal’ genes acting in opposing feed-forward loops may be used by many stem cell lineages to generate diversity.

Place, publisher, year, edition, pages
Cambridge,MA, USA: Cell Press, 2009
Keywords
neural progenitor, temporal transitions, feed-forward loops, combinatorial codes, cell fate specification
National Category
Developmental Biology
Identifiers
urn:nbn:se:liu:diva-51638 (URN)10.1016/j.cell.2009.10.032 (DOI)000272169400020 ()
Note

Original Publication: Magnus Baumgardt, Daniel Karlsson, Javier Terriente, Fernando J. Díaz-Benjumea and Stefan Thor, Neuronal Subtype Specification within a Lineage by Opposing Temporal Feed-Forward Loops, 2009, Cell, (139), 5, 969-982. http://dx.doi.org/10.1016/j.cell.2009.10.032 Copyright: Elsevier Science B.V., Amsterdam. http://www.cell.com/cellpress

Available from: 2009-11-11 Created: 2009-11-11 Last updated: 2017-12-12Bibliographically approved
Baumgardt, M., Miguel-Aliaga, I., Karlsson, D., Ekman, H. & Thor, S. (2007). Specification of neuronal identities by feedforward combinatorial coding.. PLoS biology, 5(2), 0295-0308
Open this publication in new window or tab >>Specification of neuronal identities by feedforward combinatorial coding.
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2007 (English)In: PLoS biology, ISSN 1544-9173, E-ISSN 1545-7885, Vol. 5, no 2, p. 0295-0308Article in journal (Refereed) Published
Abstract [en]

Neuronal specification is often seen as a multistep process: earlier regulators confer broad neuronal identity and are followed by combinatorial codes specifying neuronal properties unique to specific subtypes. However, it is still unclear whether early regulators are re-deployed in subtype-specific combinatorial codes, and whether early patterning events act to restrict the developmental potential of postmitotic cells. Here, we use the differential peptidergic fate of two lineage-related peptidergic neurons in the Drosophila ventral nerve cord to show how, in a feedforward mechanism, earlier determinants become critical players in later combinatorial codes. Amongst the progeny of neuroblast 5-6 are two peptidergic neurons: one expresses FMRFamide and the other one expresses Nplp1 and the dopamine receptor DopR. We show the HLH gene collier functions at three different levels to progressively restrict neuronal identity in the 5-6 lineage. At the final step, collier is the critical combinatorial factor that differentiates two partially overlapping combinatorial codes that define FMRFamide versus Nplp1/DopR identity. Misexpression experiments reveal that both codes can activate neuropeptide gene expression in vast numbers of neurons. Despite their partially overlapping composition, we find that the codes are remarkably specific, with each code activating only the proper neuropeptide gene. These results indicate that a limited number of regulators may constitute a potent combinatorial code that dictates unique neuronal cell fate, and that such codes show a surprising disregard for many global instructive cues.

National Category
Natural Sciences
Identifiers
urn:nbn:se:liu:diva-50010 (URN)10.1371/journal.pbio.0050037 (DOI)
Note
Original Publication: Magnus Baumgardt, Irene Miguel-Aliaga, Daniel Karlsson, Helen Ekman and Stefan Thor, Specification of neuronal identities by feedforward combinatorial coding., 2007, PLoS biology, (5), 2, e37. http://dx.doi.org/10.1371/journal.pbio.0050037 Licensee: PLoS Available from: 2009-10-11 Created: 2009-10-11 Last updated: 2017-12-12Bibliographically approved
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