BIOGRAPHY AND RESEARCH INTERESTS
ZFIN ID: ZDB-PERS-960805-60
The vertebrate central nervous system (CNS) is capable of highly complex functions, which are achieved in part thanks to the wide variety of neurons from which it is constructed. Thus, the development of the CNS requires that the appropriate neurons be born at the correct time and place and in the correct numbers. We are aiming to understand how these processes are controlled during development. Our work concerns three axes of research, one primarily historic and two more recent, all of which deal with various aspects of neurogenesis using the zebrafish as a model.
1) Previously, we have studied regulatory element required for the expression of the zebrafish proneural gene neurogenin1 (neurog1). We are now addressing how this bHLH transcription factor regulates its targets.More recently, we have shown that, neurog1 and a second zebrafish Atonal genes neurod4, are redundantly required for development of neurons in the olfactory epithelium.
2) The habenulae are bilateral nuclei in the epithalamus that display left-right (L/R) asymmetries of molecular markers and neural projections. Studies have shown that handedness of this asymmetry is biased by unilateral Nodal signalling. We have shown a L/R asymmetry in the pool of neurog1+ habenular progenitors and that this asymmetry is compromised in the absence of Nodal signalling. We are presently addressing the question of how Nodal signalling induces a left sided bias in habenular neurogenesis.
3) The zebrafish epiphysis is a small, light-sensitive vesicle in the epithalamus containing only two neural subtype, projection neurons or photoreceptors, and as such provides a simple system for understanding how different neural subtypes are specified. We have identified the Notch pathway as an actor in making the choice between these two cell fates. Our results suggest that at least two distinct signals are required for epiphysial neural fate specification: one as yet unknown signal for the induction of the photoreceptor fate and the other, involving Notch, for the inhibition of projection neuron traits. Via a small candidate screen, we recently identified BMP signalling as both necessary and sufficient to promote the photoreceptor fate. We have also demonstrate that crosstalk between BMP and Notch signalling is required for the inhibition of a projection neuron fate in future photoreceptors.
Lekk, I., Duboc, V., Faro, A., Nicolaou, S., Blader, P., Wilson, S.W. (2019) Sox1a mediates the ability of the parapineal to impart habenular left-right asymmetry. eLIFE. 8:
Roussigné, M., Wei, L., Tsingos, E., Kuchling, F., Alkobtawi, M., Tsalavouta, M., Wittbrodt, J., Carl, M., Blader, P., Wilson, S.W. (2018) Left/right asymmetric collective migration of parapineal cells is mediated by focal FGF signaling activity in leading cells. Proceedings of the National Academy of Sciences of the United States of America. 115(42):E9812-E9821
Collins, M.M., Maischein, H.M., Dufourcq, P., Charpentier, M., Blader, P., Stainier, D.Y. (2018) Pitx2c orchestrates embryonic axis extension via mesendodermal cell migration. eLIFE. 7:
Aguillon, R., Batut, J., Subramanian, A., Madelaine, R., Dufourcq, P., Schilling, T.F., Blader, P. (2018) Cell-type heterogeneity in the early zebrafish olfactory epithelium is generated from progenitors within preplacodal ectoderm. eLIFE. 7
Delfino-Machín, M., Madelaine, R., Busolin, G., Nikaido, M., Colanesi, S., Camargo-Sosa, K., Law, E.W., Toppo, S., Blader, P., Tiso, N., Kelsh, R.N. (2017) Sox10 contributes to the balance of fate choice in dorsal root ganglion progenitors. PLoS One. 12:e0172947
Halluin, C., Madelaine, R., Naye, F., Peers, B., Roussigné, M., Blader, P. (2016) Habenular Neurogenesis in Zebrafish Is Regulated by a Hedgehog, Pax6 Proneural Gene Cascade. PLoS One. 11:e0158210
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., Carl, M. (2014) Tcf7l2 Is Required for Left-Right Asymmetric Differentiation of Habenular Neurons. Current biology : CB. 24(19):2217-27
Garric, L., Ronsin, B., Roussigné, M., Booton, S., Gamse, J.T., Dufourcq, P., Blader, P. (2014) Pitx2c ensures habenular asymmetry by restricting parapineal cell number. Development (Cambridge, England). 141:1572-9
Kishimoto, N., Asakawa, K., Madelaine, R., Blader, P., Kawakami, K., and Sawamoto, K. (2013) Interhemispheric asymmetry of olfactory input-dependent neuronal specification in the adult brain. Nature Neuroscience. 16(7):884-8
Quillien, A., Blanco-Sanchez, B., Halluin, C., Moore, J.C., Lawson, N.D., Blader, P., and Cau, E. (2011) BMP signaling orchestrates photoreceptor specification in the zebrafish pineal gland in collaboration with Notch. Development (Cambridge, England). 138(11):2293-2302
Chapouton, P., Skupien, P., Hesl, B., Coolen, M., Moore, J.C., Madelaine, R., Kremmer, E., Faus-Kessler, T., Blader, P., Lawson, N.D., and Bally-Cuif, L. (2010) Notch activity levels control the balance between quiescence and recruitment of adult neural stem cells. The Journal of neuroscience : the official journal of the Society for Neuroscience. 30(23):7961-7974
Langevin, L.M., Mattar, P., Scardigli, R., Roussigne, M., Logan, C., Blader, P., and Schuurmans, C. (2007) Validating in utero electroporation for the rapid analysis of gene regulatory elements in the murine telencephalon. Developmental dynamics : an official publication of the American Association of Anatomists. 236(5):1273-1286
Carney, T.J., Dutton, K.A., Greenhill, E., Delfino-Machin, M., Dufourcq, P., Blader, P., and Kelsh, R.N. (2006) A direct role for Sox10 in specification of neural crest-derived sensory neurons. Development (Cambridge, England). 133(23):4619-4630
Dufourcq, P., Roussigne, M., Blader, P., Rosa, F., Peyriéras, N., and Vriz, S. (2006) Mechano-sensory organ regeneration in adults: The zebrafish lateral line as a model. Molecular and cellular neurosciences. 33(2):180-187
Etard, C., Behra, M., Ertzer, R., Fischer, N., Jesuthasan, S., Blader, P., Geisler, R., and Strähle, U. (2005) Mutation in the delta-subunit of the nAChR suppresses the muscle defects caused by lack of Dystrophin. Developmental dynamics : an official publication of the American Association of Anatomists. 234(4):1016-1025
Blader, P., Lam, C.S., Rastegar, S., Scardigli, R., Nicod, J.C., Simplicio, N., Plessy, C., Fischer, N., Schuurmans, C., Guillemot, F., and Strähle, U. (2004) Conserved and acquired features of neurogenin1 regulation. Development (Cambridge, England). 131(22):5627-5637
Hans, S., Scheer, N., Riedl, I., Von Weizsacker, E., Blader, P., and Campos-Ortega, J.A. (2004) her3, a zebrafish member of the hairy-E(spl) family, is repressed by Notch signalling. Development (Cambridge, England). 131(12):2957-2969
Albert, S., Müller, F., Fischer, N., Biellmann, D., Neumann, C., Blader, P., and Strähle, U. (2003) Cyclops-independent floor plate differentiation in zebrafish embryos. Developmental dynamics : an official publication of the American Association of Anatomists. 226(1):59-66
Rastegar, S., Albert, S., Le Roux, I., Fischer, N., Blader, P., Müller, F., and Strähle, U. (2002) A floor plate enhancer of the zebrafish netrin1 gene requires Cyclops (Nodal) signalling and the winged helix transcription factor FoxA2. Developmental Biology. 252(1):1-14
Dickmeis, T., Aanstad, P., Clark, M., Fischer, N., Herwig, R., Mourrain, P., Blader, P., Rosa, F., Lehrach, H., and Strähle, U. (2001) Identification of nodal signaling targets by array analysis of induced complex probes. Developmental dynamics : an official publication of the American Association of Anatomists. 222(4):571-580
Müller, F., Albert, S., Blader, P., Fischer, N., Hallonet, M., and Strähle, U. (2000) Direct action of the Nodal-related signal Cyclops in induction of sonic hedgehog in the ventral midline of the CNS. Development (Cambridge, England). 127(18):3889-3897
Müller, F., Blader, P., Rastegar, S., Fischer, N., Knochel, W., Strähle, U. (1999) Characterization of zebrafish smad1, smad2 and smad5: the amino-terminus of Smad1 and Smad5 is required for specific function in the embryo. Mechanisms of Development. 88(1):73-88
Blader, P., Fischer, N., Gradwohl, G., Guillemot, F., and Strähle, U. (1997) The activity of Neurogenin1 is controlled by local cues in the zebrafish embryo. Development (Cambridge, England). 124:4557-4569
Strähle, U., Jesuthasan, S., Blader, P., Garcia-Villalba, P., Hatta, K., and Ingham, P.W. (1997) one-eyed pinhead is required for development of the ventral midline of the zebrafish (Danio rerio) neural tube. Genes and function. 1:131-148
Rauch, G.-J., Hammerschmidt, M., Blader, P., Schauerte, H.E., Strähle, U., Ingham, P.W., McMahon, A.P. and Haffter, P. (1997) WNT5 is required for tail formation in the zebrafish embryo. Cold Spring Harbor symposia on quantitative biology. 62:227-233