Patrik Ernfors

Group members:
Igor Adameyko, postdoc
Sergi Aranda, postdoc
Albert Blanchard, postdoc
Boris Eleuteri, postdoc
Ruani Fernando, postdoc
Marina Franck, PhD stud
Alessandro Furlan, PhD stud
Satish Kitambi, postdoc
Francois Lallemend, postdoc
Moritz Lubke, postdoc
Dmitry Usoskin, postdoc

PATRIK ERNFORS
Department of Medical Biochemistry & Biophysics (MBB)
Patrik.Ernfors@ki.se

We are interested in the genetic and epigenetic control of neuronal survival, differentiation and cell-type specification during development. We study how external signals are coordinated with cell competence to generate different types of sensory neurons, how these establish functional connections with the CNS and the signals that control sensory neuron survival.

We are interested to understand how progenitor cells are driven to adopt a specific fate among the many possible fates during nervous system development. The neural crest is technically and conceptually an ideal model system to resolve this question. The principle of cell fate commitment involves patterning morphogens initiating cascades of combinations of transcription factors that together control cell programs. Both induction of the neural crest in the neural plate and segregation of postmigratory neural crest to different neural crest lineages are under strict control in a temporo-spatial manner by the expression of signals in adjacent somites folding into dermamyotomes and in spinal cord. By changing their competence to respond to an extrinsic signal, cells are able to diversify the possible outcomes of a given signaling pathway. This is likely to occur through changes in the complement of receptors and transcription factors (intrinsic, cell-autonomous components) that are expressed by the cell at any given time and in the way in which these interact with elements from the signaling pathways. We are also interested to understand how genetic and epigenetic signals integrate during cell differentiation. Integration can occur at the promoters of target genes or by the formation of multiprotein complexes between genetically and epigenetically controlled factors. Finally, we are interested in understanding how gene programs directing neuronal diversification are integrated with those determining the establishment of specific points of axonal projections and contacts in the central nervous system underlying development of a functional circuit.

We have identified sets of key transcription factors participating in these processes and use cell/molecular tools as well as defined functional assay systems that combined can dissect in fine detail resolve the mechanisms behind these developmental processes. Model systems for functional studied include: 1) As in vitro model system we use boundary cap neural crest stem cell cultures. Electroporation and lentivirus vectors are used for introducing genetic material into the cells. 2) For in vivo studies the chick is readily amenable for in ovo electroporation of overexpressing, dominant negative or RNAi constructs of candidate genes as well as for transplantation studies of cellular competence. 3) Gene targeting in the mouse for conditionally eliminate gene function/ lineage tracing.

5 SELECTED PUBLICATIONS:

Adameyko I., Lallemend F., Aquino J.B., Pereira J.A., Topilko P., Müller T., Fritz N., Beljajeva A., Mochii M., Liste I., Usoskin D., Suter U., Birchmeier C., and Ernfors P. (2009) Schwann cell precursors from nerve innervation are a cellular origin of melanocytes in skin. Cell 139, 366-379.

Baudet C., Pozas E., Adameyko I., Andersson E., Ericson J., and Ernfors P. (2008) Retrograde signaling onto Ret during motor nerve terminal maturation. J. Neurosci. 28, 963-975.

Andäng M., Hjerling-Leffler J., Moliner A., Pozas E., Nanou E., Castelo-Branco G., Halliez S., Koltzenburg M., Bryja V., Charnay P., El Manira, A., Ibáñez C.F., and Ernfors P. (2008) A histone H2AX-dependent GABAAR controlled regulation of stem cell proliferation. Nature 451, 460-464.

Marmigère F., and Ernfors P. (2007) Specification and connectivity of neuronal subtypes in the sensory lineage. Nat. Rev. Neurosci. 8, 114-127.

Marmigère F., Montelius A., Wegner M., Groner Y., and Ernfors, P. (2006) The Runx1/AML1 transcription factor selectively regulates development and survival of the TrkA nociceptive sensory neurons. Nat. Neurosci. 9, 180-187.

LINKS:

For more information, please visit our lab website.