Molecular neurobiology

Diogo Castro

The main goal of the research group is to understand how global programmes of gene expression are regulated during vertebrate neurogenesis.

Along the neuronal lineage, an intrinsic programme that relies on the activity of transcription factors and the epigenetic landscape coordinates the progression of progenitors throughout distinct cellular stages.

Such intrinsic programme integrates information from local extracellular signals (e.g. through cell to cell contact) or from long range cues (e.g. secreted factors), resulting in the progression of a coherent programme of cellular differentiation that requires governing the expression of a large number of genes.

In order to understand the regulatory logic of neurogenesis, they focus the studies on proneural transcription factors (e.g.Mash1/Ascl1) that function as master regulators of neurogenesis by coordinating the various components of the differentiation programme.

Researchers investigate how Ascl1 interacts with the chromatin landscape and other transcriptional networks, in particular the Notch pathway. In addition, they are also interested in understanding how key transcriptional networks that underlie neural stem cell function are hijacked during tumorigenesis.

In this context researchers use cancer stem cell models of Glioblastoma Multiform, the most frequent and aggressive of brain tumours. In our research we use a multidisciplinary approach, combining mouse genetics, genomics and stem cell biology techniques.

Publications

Vasconcelos, F.F., Sessa, A., Laranjeira, C., Raposo, A.A.S.F., Teixeira, V., Hagey, D.W., Tomaz, D.M., Muhr, J., Broccoli, V., Castro, D.S. (2016) MyT1 counteracts the neural progenitor program to promote vertebrate neurogenesis Cell Rep. 17(2) : 469–483
Singh, S., Howell, D., Trivedi, N., Kessler, K., Ong, T., Rosmaninho, P., Raposo, A.A.S.F., Robinson, G., Roussel, M.F., Castro, D.S.* , Solecki, D.J.* *Shared corresponding author (2016) Zeb1 controls neuron differentiation and germinal zone exit by a mesenchymal-epithelial-like transition. eLife 5 : e12717

Raposo, A.A.S.F., Vasconcelos, F.F., Drechsel, D., Marie, C., Johnston, C., Dolle, D., Bithell, A., Guillotin, S., van den Berg, D.L.C., Etwiller, L., Flicek, P., Crawford, G.E., Parras, C.M, Berninger, B., Buckley, N.J., Guillemot, F., Castro, D.S. (2015) Ascl1 coordinately regulates gene expression and the chromatin landscape during neurogenesis Cell Rep pii : S2211-1247(15)00171-0
Mateo, J.L., van den Berg, D.L., Haeussler, M., Drechsel, D., Gaber, Z.B., Castro, D.S. , Robson, P., Crawford, G.E., Flicek, P., Ettwiller, L., Wittbrodt, J., Guillemot, F., Martynoga, B. (2015) Characterization of the neural stem cell gene regulatory network identifies OLIG2 as a multifunctional regulator of self-renewal Genome Res 25(1) : 41-56
Vasconcelos, F.F., Castro, D.S. (2014) Transcriptional control of vertebrate neurogenesis by the proneural factor Ascl1 Front Cell Neurosci 8 : 412
Borromeo, M.D., Meredith, D.M., Castro, D.S. , Chang, J.C., Tung, K.C., Guillemot, F., Johnson, J.E. (2014) A transcription factor network specifying inhibitory versus excitatory neurons in the dorsal spinal cord Development 141 : 2803-2812
Wapinski, O.L., Vierbuchen, T., Qu, K., Lee, Q.Y., Chanda, S., Fuentes, D.R., Giresi, P.G., Ng YH, Marro, S., Neff, N.F., Drechsel, D., Martynoga, B., Castro, D.S. , Webb, A.E., Südhof TC, Brunet, A., Guillemot, F., Chang, H.Y., Wernig, M. (2013) Hierarchical mechanisms for direct reprogramming of fibroblasts to neurons Cell 155(3) : 621-35
Castro, D.S. , Guillemot, F. (2011) Old and new functions of proneural factors revealed by the genome-wide characterization of their transcriptional targets Cell Cycle 10(23) : 4026-4031
Castro, D.S.* , Martynoga, B., Parras, C., Ramesh, V., Pacary, E., Johnston, C., Drechsel, D., Lebel-Potter, M., Galinanes-Garcia, L., Hunt, C., Dolle, D., Bithell, A., Ettwiller L, Buckley, N., Guillemot, F. *Corresponding author (2011) A novel function of the proneural factor Ascl1 in progenitor proliferation identified by genome-wide characterization of its targets Genes & Dev 25 : 930-945