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Johan Ericson“Transcriptional interpretation of graded Shh signalling in neural pattern formation”

Abstract :


The establishment of cellular diversity in the developing CNS is influenced by mechanisms that operate in space and over time, so that functionally distinct neurons are born at specific positions and at defined time points in the developing neural tube.
The signalling molecule Sonic hedgehog (Shh) acts in a graded fashion to control the spatial patterning of neuronal subtypes in the ventral neural tube. A key role for Shh in this process is to control the region-specific expression of transcriptional determinants, which subsequently trigger subtype-specific differentiation programs in differentiating neurons. In neural patterning, it has remained unclear how graded Shh signalling is interpreted and translated at genomic levels into region- and tissue-specific transcriptional outputs. In my presentation, I will present data indicating that a repressive gene regulatory network determines the spatial patterning of genes downstream of graded Shh signalling, and provide evidence for a generally applicable and unexpectedly simple transcriptional paradigm that explains how Shh signalling can elicit tissue-specific responses during embryogenesis. Finally, I will address how the basic characterisation of neural development can be applied to effectively control the differentiation of pluripotent stem cells into clinically important neuronal subtypes, including dopaminergic and serotonergic neurons.

 

Selected publications

Panman, L., Andersson, E., Alekseenko, Z., Hedlund, E., Kee, N., Mong, J., Uhde, C., Deng, Q., Sandberg, R., Stanton, L.W., Ericson, J.* and Perlmann, T.* *Co-senior and corresponding authors. Transcription Factor-Induced Lineage Selection of Stem Cell-Derived Neural Progenitor Cells.Cell Stem Cell 8 (2011) 663-675.
Lek, M., Dias J.M., Marklund, U., Uhde, C.W., Kurdija, S., Lei, Q., Sussel, L., Rubenstein, J.L., Matise, M., Arnold, H-H., Jessell, T.M. and Ericson, J. A homeodomain feedback circuit underlies step-function interpretation of a Shh morphogen gradient during ventral neural patterning. Development 137, (2010) 4051-4060.

Marklund, U., Hansson, E.M., Sundström, E., Hrabéde Angelis, M., Przemeck, G.K., Lendahl, U., Muhr, J. and Ericson, J. Domain specific control of neurogenesis through the patterned regulation ofDelta1 and Jagged1 expression. Development 137, (2010) 437-445.

Friling, S., Andersson, E., Thompson, L., Jönsson, M., Hebsgaard, J.B., Nanou, E., Alekseenko, Z., Marklund,U., Kjellander, S., Volakakis,N., Hovatta, O., El Manira, A., Björklund, A., Perlmann, T. and Ericson, J.
Efficient Production of Mesencephalic Dopamine Neurons by Lmx1a Expression in Embryonic Stem Cells. Proc. Natl. Acad. Sci. USA 106, (2009) 7613-8. Epub 2009 Apr 21.

Andersson, E., Tryggvason, U., Deng, Q., Friling, S., Alakseenko, Z., Robert, B., Perlmann, T., and Ericson, J.
Identification of intrinsic determinants of midbrain dopamine neurons. Cell 124, (2006) 393-405.

Mireille Montcouquiol et Laurent Groc.