The genetic network downstream of tcf mediated Wnt/beta-catenin signaling during the establishment of brain asymmetries
Final Report Abstract
With the help from the DFG, we have reached several milestones to understand asymmetric brain development and function. On the molecular level, we have identified the Wnt signaling molecule Tcf7l2 as a key regulator of all habenular neuronal types and habenular asymmetry. On the network level, we have uncovered the previously unknown origin of the ventral habenula. Furthermore, the development of novel tools and an unprecedented in vivo imaging assay in combination with focal laser ablations allowed us to unravel a novel mechanism of neural network development. On the functional level, we have established an amenable brain structure as a model to study the functional importance of neuroanatomical asymmetries. Our work has opened the field for further investigations on all three levels. The conserved habenular neurotransmittersystem is a central regulator of various behaviors and has been implicated to play a key role in the pathophysiology of depression and schizophrenia. Therefore, it will be intriguing to further translate our findings into the medical field.
Publications
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(2012). Don’t be afraid to set up your fish facility. Zebrafish 9(3): 120-125
McNabb, A., Scott, K., von Ochsenstein, E., Seufert, K. and Carl, M.
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(2012). Habenula circuit development: past, present, and future. Frontiers in Neuroscience 6:51
• Beretta, C.A., Dross, N., Guiterrez-Triana, J.A., Ryu, S. and Carl, M.
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(2013). The ventral habenulae in zebrafish develop in prosomere 2 dependent on Tcf7l2 function, Neural Development 8(1):19
Beretta, C.A., Dross, N., Bankhead, P., and Carl, M.
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(2013). The Wnt/beta-catenin signaling pathway establishes neuroanatomical asymmetries and their laterality. Mech. Dev. 130: 330-335
Hüsken, U. and Carl, M.
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(2014). Left/right asymmetry is required for the habenulae to respond to both visual and olfactory stimuli. Current Biology 24(4):440-445
Dreosti, E., Llopis, N.V., Carl, M., Yaksi E., and Wilson, S.W.
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(2014). Tcf7l2 is required for left-right asymmetric differentiation of habenular neurons. Current Biology 24(19):2217-2227
Hüsken, U., Stickney, H.L., Gestri, G., Bianco, I.H., Faro, A., Young, R.M., Roussigne, M., Hawkins, T.A., Beretta, C.A., Brinkmann, I., Paolini A., Jacinto, R., Albadri, S., Dreosti, E., Tsalavouta, M., Schwarz, Q., Cavodeassi, F., Barth, A.K., Wen, L., Zhang, B., Blader, P., Yaksi, E., Poggi, L., Zigman, M., Lin, S., Wilson, S.W., and Carl, M.
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(2016). Tracking cells in GFP- transgenic zebrafish using the photoconvertible PSmOrange system. J. Vis. Exp. (108), e53604
Beretta, C.A., Dross, N., Engel, U., and Carl, M.
