Almost 2 years and half have passed since I started my lab at the Neuroscience Dept. at KI, with the essential financial support of the Ragnar Soderberg foundation.
Ragnar Söderbergforskare i medicin // År: 2012 //
Anslagsförvaltare: Karolinska Institutet // Belopp: 8 000 000 kr
One of the fundamental issues in the field of developmental biology is to understand the mechanisms that control the identity of individual cells and their connections within their environment. The task of establishing appropriate cell types and patterns of connectivity is uniquely complex in the nervous system, where a diverse variety of neuronal types integrate together to form the components and circuits indispensable for nervous system function.
Here, using state of the art technologies, we propose to identify the molecular network that, through iterative interactions, controls each step of the developmental programs of proprioceptive and nociceptive sensory neurons, from birth, through diversification, axonal growth and synaptic connectivity. In parallel, we propose for the first time to identify, anatomically (Connectome) and genetically (Transcriptome) the different pools of sensory neurons that connect individual forelimb muscles to the central nervous system, a specific wiring which reflects the critical contribution of sensory feedback pathways to the coordination of movement.
Over the long term, these studies will provide significant insights into the fundamental principles involved in the proper formation of the nervous system as well as new strategies for the design of more effective pain therapies and for promoting topographically specific nerve regeneration following spinal injury.
1. Lallemend F°, Aquino JB, Castelo-Branco G, Villaescusa C, Levanon D, Sinha I, Hadjab S, Sterzenbach U, Franck M, Linnarsson S, Kharchenko O, Adameyko I, Groner Y, Turner E and Ernfors P°. Positional differences of intrinsic axon growth rates between sensory neurons encoded by Runx3. Revised in EMBO J.
2. Defourny J, Poirrier AL, Lallemend F, Moser T, Soriano E, Nguyen L, Vanderhaeghen P, Moonen G and Malgrange B. Differential expressions of ephrin and Eph genes are required for specific afferent targeting to hair cells in the cochlea. Revised in Nature Communication.
3. Lallemend F° and Ernfors P°. Molecular interactions underlying the specification of sensory neurons. Trends Neurosci. DOI:10.1016/j.tins.2012.03.006.
4. Adameyko I, Lallemend F, Furlan A, Zinin N, Kitambi S, Blanchard A, Favaro R, Nicolis S, Lubke M, Muller T, Birchmeier C, Suter U, Takahashi Y and Ernfors P. Sox2 and MITF cross regulatory interactions establish progenitor and melanocyte lineages in the cranial neural crest. Development. 2012 Nov;139(2):397-410.
5. Abdo H, Li L, Lallemend F, Bachy I, Xu XJ, Rice FL and Ernfors P. Dependence on the transcription factor Shox2 for specification of sensory neurons conveying discriminative touch. Eur J Neurosci. 2011 Nov; 34(10):1529-41.
6. Defourny J, Lallemend F, Malgrange B. Structure and development of cochlear afferent innervation in mammals. Am J Physiol Cell Physiol. 2011 Oct;301(4):C750-61.
7. Adameyko I° and Lallemend F°. Glial versus Melanocyte Cell Fate Choice: Schwann Cell Precursors as a Cellular Origin of Melanocytes. Cell. Mol. Life Sciences. 2010; 67(18):3037-55.
8. Lallemend F* , Adameyko I* , Aquino JB, Topilko P, Pereira JA, Müller T, Fritz N, Beljajeva A, Mochii M, Liste I, Usoskin D, Suter U, Birchmeier C and Ernfors P. Schwann Cell Precursors from Nerve Innervation is a Cellular Origin of Melanocytes in Skin. Cell. 2009 Oct 16; 139:366-79. F1000: ranked as 10 (exceptional)
9. Lallemend F* , Aquino JB* , Marmigère F, Adameyko II, Golemis EA, Ernfors P. Dynamic levels of the signaling molecule Nedd9 regulate migration of neural crest cells. Neuroscience. 2009 Sep 15; 162(4):1106-19.
10. Aquino JB, Marmigère F, Lallemend F, Lundgren TK, Villar MJ, Wegner M, Ernfors P. Differential expression and dynamic changes of murine NEDD9 in progenitor cells of diverse tissues. Gene Expression Patterns. 2008 April; 8(4): 217-26.