The human nervous system contains billions of cells and thousands of cell types. Cells differ from each other in many ways, including in their shape and in the type of neurotransmitter they express. Each type of cell furthermore needs to be generated at the correct place, correct time, and in proper numbers.

The combined effect of great numbers, great diversity and great fidelity constitutes the very basis for the enormously complex functions of the nervous system, such as homeostasis, learning/memory and behavior. However, due to the complexity of the nervous system we still have major knowledge gaps in our understanding of how different cell types are specified and how proliferation is controlled.

Resolving these fundamental issues will likely be important for our understanding not only of normal development, but also of various neurological disorders and cancer, since there is increasing awareness that many such diseases may be caused by dysfunctional developmental programs, including proliferation control.

What drives the anterior expansion of the mammalian central nervous system?

A striking feature of the central nervous system (CNS) pertains to the anterior expansion of the brain relative to the nerve cord. This feature is evolutionarily conserved from annelids to humans. Brain expansion becomes increasingly pronounced during evolution and reaches its zenith in mammals, as visualized by the large cortex. The evolutionary expansion of the brain has been instrumental for the higher cognitive functions associated with primates, including humans. However, there are major knowledge gaps in our understanding of the genetic and cellular underpinnings driving anterior CNS expansion. This project investigates the genetic forces that have driven the evolution and expansion of the brain, and will impact our views on the origin of the large human brain.

Decoding cell specification in the developing mammalian hypothalamus

The hypothalamus is a small brain structure that acts as a master homeostatic regulator, controlling energy and fluid balance, thermoregulation, sleep-wake states, stress responses, growth and reproduction, as well as emotional and social behaviours.

The hypothalamus can play this plethora of complex functions because it its staggering neuronal diversity, with hundreds of different neuronal cell types. The importance of this brain structure is further underscored by the large number of disorders aligned to abnormal hypothalamic development. To understand the underlying mechanisms of these developmental disorders we need to define the basic tenets that control hypothalamic development. The aim of these studies is the spatiotemporal decoding of mouse hypothalamic development, including the identification of distinct stem cell types and their lineages, as well as the functional analysis of epigenetic and transcriptional regulators steering these events.

2019

Bahrampour, S, Jonsson, C, Thor, S. (2019). Brain expansion promoted by Polycomb-mediated anterior enhancement of a neural stem cell proliferation program. PLoS Biol, 17(2): e3000163. PMID: 30807568. DOI: 10.1371/journal.pbio.3000163.

Stratmann, J, Ekman, H, Thor, S. (2019). Branching gene regulatory network dictating different aspects of neuronal cell identity. Development, 146(6), dev174300. PMID: 30837222. DOI: 10.1242/dev.174300.

2018

Yaghmaeian Salmani, B, Monedero Cobeta, I, Rakar, J, Bauer, S, Rodriguez Curt J, Starkenberg, A, Thor, S. (2018). Evolutionary conserved anterior expansion of the central nervous system promoted by a conserved PcG-Hox program. Development, 145(7): 1-17 (dev160747). PMID: 29530878; DOI: 10.1242/dev.160747.

Monedero Cobeta, I, Bivik C, Li, J, Yu, P, Thor, S, Benito-Sipos, J. (2018). Specification of Drosophila neuropeptidergic neurons by the splicing factor Brr2. PLoS Genet, 14(8):e1007496. PMID: 30133436; DOI: 10.1371/journal.pgen.1007496.

2017

Monedero Cobeta, I, Salmani, BY, Thor, S. (2017). Anterior-posterior gradient in neural stem and daughter cell proliferation governed by spatial and temporal Hox control. Curr Biol, 27(8):1161-1172. PMID: 28392108; DOI: 10.1016/j.cub.2017.03.023.

Stratmann, J, Thor, S. (2017). Neuronal cell fate specification by the molecular convergence of different spatio-temporal cues on a common initiator terminal selector gene. PLoS Genet, 13(4):e1006729. PMID: 28414802; DOI: 10.1371/journal.pgen.1006729.

Bahrampour, S, Gunnar, E, Jonsson, C, Ekman, H, Thor, S. (2017). Neural lineage progression controlled by a temporal proliferation program. Dev Cell, 43(3): 332-348. PMID: 29112852; DOI: 10.1016/j.devcel.2017.10.004.

2016

Bivik, C, MacDonald, R, Gunnar, E, Mazouni, K, Schweisguth, F, Thor, S. (2016). Control of neural daughter cell proliferation by multi-level Notch/Su(H)/E(spl)HLH signaling. PLoS Genet, 12(4):e1005984. PMID: 27070787; DOI: 10.1371/journal.pgen.1005984.

Gunnar, E, Bivik, C, Starkenberg, A, Thor, S. (2016). sequoia controls the TypeI>0 daughter proliferation switch in the Drosophila nervous system. Development, 143(20):3774-3784. PMID: 27578794; DOI: 10.1242/dev.139998.

Stratmann, J1, Gabilondo, H1, Benito-Sipos, J, Thor, S. (2016). Neuronal cell fate diversification controlled by sub-temporal action of Kruppel. eLife, Oct 14;5. pii: e19311. 1) equal contribution. PMID: 27740908; DOI: 10.7554/eLife.19311.

2009 - 2015

Baumgardt, M, Karlsson, D, Félix, JT, DíazBenjumea, FJ, Thor, S. (2009). Neuronal sub-type specification within a lineage by opposing temporal feed-forward loops. Cell, 139(5):969-82. PMID: 19945380; DOI: 10.1016/j.cell.2009.10.032.

Karlsson, D, Baumgardt, M, Thor, S. (2010). Segment-specific neuronal subtype specification by the integration of anteroposterior and temporal cues. PLoS Biology, 8(5):e1000368. PMID: 20485487; DOI: 10.1371/journal.pbio.1000368.

Benito-Sipos, J, Ulvklo, C, Gabilondo, H, Baumgardt, M, Angel, A, Torroja, L, Thor, S. (2011). Seven up acts as a temporal factor during two different stages of neuroblast 5-6 development. Development, 138(24):5311-5320. PMID: 22071101; DOI: 10.1242/dev.070946.

Ulvklo, C, MacDonald, R, Bivik, C, Baumgardt, M, Karlsson, D, Thor, S. (2012). Control of neuronal cell fate and numbers by integration of distinct daughter cell proliferation modes with temporal progression. Development, 139(4):678-89. PMID: 22241838; DOI: 10.1242/dev.074500.

Losada-Pérez, M, Gabilondo, H, Molina, I, Turiegano, E, Torroja, L, Thor S, Benito-Sipos, J. (2013). Klumpfuss controls FMRFamide expression by enabling BMP signaling within the NB 5-6 lineage. Development, 140(10): 2181-8. PMID: 23633512; DOI: 10.1242/dev.089748.

Baumgardt, M*, Karlsson, D*, Salmani, BY, Bivik, C, MacDonald, R, Gunnar, E, Thor, S. (2014). Global programmed switch in neural daughter cell proliferation mode triggered by a temporal gene cascade. Dev Cell, 30(2):192-208. (*equal contribution). PMID: 25073156; DOI: 10.1016/j.devcel.2014.06.021.

Bivik, C, Bahrampour, S, Ulvklo, C, Nilsson, P, Angel, A, Fransson, F, Lundin, E, Renhorn, J, Thor, S. (2015). Novel genes involved in controlling specification of Drosophila FMRFamide neuropeptide cells. Genetics, 200(4):1229-44. PMID: 26092715; DOI: 10.1534/genetics.115.178483.