Important early events in neurogenesis are proving elusive and difficult to define. One example is the events that underlie the specification of neural stem cells, both in terms of number and cell types, which is a consequence of the processes controlling neuroepithelial cell proliferation and the transition of their progeny into neural stem cells. We have characterized a Drosophila glial niche that regulates early neurogenesis and that is defined by the expression and activity of the conserved microRNA, miR-8 (miR-200 in humans). This work (Morante et al., 2013) has outlined a new paradigm to explain early neurogenesis in the fly brain that could also apply to vertebrates. Hence, our research has two main goals: 1) to define the intrinsic cues responsible for balancing neuroepithelial self-renewal against the switch towards neuroepithelial-neural stem cell specification in flies and vertebrates; and 2) to define the interplay of extrinsic signals that govern these processes. We employ a combined approach in which genome-wide transcriptomic analysis of neuroepithelial cells and cells in the transition zone, or of glia and neuroepithelial cells, will help to identify candidate cues in the intrinsic and extrinsic controls underlying the earliest steps in neurogenesis, respectively. In parallel, we use genetic screening using transgenic RNAi and gene overexpression under the control of specific cell-type promoters to functionally validate genes and establish in vivo how gene alterations impinge on neuroepithelial cell behavior to neural stem cell specification. Furthermore, we will investigate whether similar mechanisms operate in embryonic vertebrates during early neurogenesis. Thus, defining the pathways and interplay of intrinsic and niche-derived cues in earliest events of neurogenesis will pave the way to better understand stem cell-based neurodevelopmental diseases and brain tumors.

Representative Publications

Vallejo DM.* , Juarez-Carreño S.*, Bolivar J., Morante J.**, Dominguez M.** " A brain circuit that synchronizes growth and maturation revealed through Dilp8 binding to Lgr3. " Science . 350(6262) , - aac6767 ( 2015 ) * Equal contribution ** Co-corresponding authors

Morante J.* , Vallejo DM., Desplan C., Domínguez M. " The conserved mir-8/mir-200 microRNA defines a glial niche that controls neuroepithelial expansion and neuroblast generation in Drosophila. " Developmental Cell . 27(2) , 174 - 187 ( 2013 ) * Corresponding author

Li X. , Erclik T., Bertet C., Chen Z., Voutev R., Venkatesh S., Morante J., Celik A., Desplan C. " Temporal patterning of Drosophila medulla neuroblasts controls neural fates. " Nature . 498(7455) , 456 - 462 ( 2013 )

Morante J. , Erclik T., Desplan C. " Cell migration in Drosophila optic lobe neurons is controlled by eyeless/Pax-6. " Development . 138(4) , 687 - 693 ( 2011 )

Morante J. , Desplan C. " The color vision circuit in the medulla of Drosophila. " Current Biology . 18(8) , 553 - 565 ( 2008 )