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PD Dr. Matthias Carl

Establishment of Left-Right Asymmetric Neural Circuits

Every human can perform several tasks simultaneously. One reason for this multifunctionality is left-right differences in brain performance. If and how these functional asymmetries may correlate with anatomical brain asymmetries and influence our daily life and behavior is still a fundamental question in neuroscience. To assess this enigma we need to elucidate the development of a left-right asymmetric neural circuit and elucidate the genetic network important for its establishment.

We use the conserved zebrafish habenular neural circuit as a model and combine genetics, transgenesis and in vivo confocal time-lapse imaging to elucidate the function of the Wnt/beta-catenin signalling in the establishment of neuroanatomical asymmetries.

The habenular neural network. The dorsal habenular nuclei (dHb) comprise the asymmetrically large lateral (red) and medial (blue) sub-nuclei. Their neurons project into the dorsal and ventral interpeduncular nucleus (IPN) respectively. Ventral habenular (green) axons innervate the median raphe (MR). All these structures are labelled in Et(-1.0otpa:mmGFP)hd1 transgenic embryos at 4 days; dorsal view, anterior to the top. L, left; p, pineal; pp, parapineal; r, right. (Scheme modified after Beretta et al., 2012)

Selection of recent publications

  1. Beretta CA, Dross N, Guiterrez-Triana JA, Ryu S, Carl M. Habenula circuit development: past, present, and future. Front Neurosci 2012; 6: 51.
  2. Beretta CA, Dross N, Bankhead P, Carl M. The ventral habenulae of zebrafish develop in prosomere 2 dependent on Tcf7l2 function. Neural Dev 2013; 8: 19.
  3. Demir K, Kirsch N, Beretta CA, et al. RAB8B is required for activity and caveolar endocytosis of LRP6. Cell Rep 2013; 4(6):1224-34.
  4. Hüsken U, Carl M. The Wnt/beta-catenin signaling pathway establishes neuroanatomical asymmetries and their laterality. Mech Dev 2013; 130(6-8): 330-5.
  5. Dreosti E, Vendrell Llopis N, Carl M, Yaksi E, Wilson SW. Left-right asymmetry is required for the habenulae to respond to both visual and olfactory stimuli. Curr Biol 2014; 24(4): 440-5.
  6. Hüsken U, Stickney HL, Gestri G, et al. Tcf7l2 is required for left-right asymmetric differentiation of habenular neurons. Curr Biol 2014; 24(19): 2217-27.
  7. Mwafi N, Beretta CA, Paolini A, Carl M. Divergent Wnt8a gene expression in teleosts. PLoS One 2014; 9(1): e85303.
  8. Beretta CA, Dross N, Engel U, Carl M. Tracking Cells in GFP-transgenic Zebrafish Using the Photoconvertible PSmOrange System. J Vis Exp 2016; (108).
  9. Kopajtich R, Murayama K, Janecke AR, et al. Biallelic IARS Mutations Cause Growth Retardation with Prenatal Onset, Intellectual Disability, Muscular Hypotonia, and Infantile Hepatopathy. Am J Hum Genet 2016; 99(2): 414-22.
  10. Beretta, C.A., Dross, N., Guglielmi, L., Bankhead, P., Soulika, M., Gutierrez-Triana, J.A., Paolini, A., Poggi, L., Falk, J., Ryu, S., Kapsimali, M., Engel, U., Carl, M. Early commissural diencephalic neurons control habenular axon extension and targeting. Current Biology 2017; 27:270-78.

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