A molecular dissection of neural induction

Trevers K, Lu HC, Anderson C, Strobl AC, Palinkasova B, Filipkova L, Perez-Campos L, Moncaut N, de Almeida IM and Stern CD

Dept Cell & Developmental Biology, University College London, United Kingdom.

Neural induction is the process, during normal development, when the future neural plate becomes specified and set aside from the rest of the ectoderm, under the influence of signals emanating from a special region of the embryo, the "organizer". Neural induction is generally viewed as a switch, assuming a single event. To explore the nature of such a developmental switch, we have undertaken a detailed spatio-temporal analysis of the process at the molecular level. We establish that neural induction occurs over many hours and involves a hierarchical cascade of more than 200 transcription factors. Their expression is regulated by cooperation between several signalling pathways acting both sequentially and in parallel. We also uncover the epigenetic regulation of this cascade by mapping chromatin marks and revealing many regulatory elements associated with these transcription factors. We generate a dynamic Gene Regulatory Network, representing the interactions underlying the neural induction process. Therefore the switch between neural and non-neural ectoderm involves a highly complex network of events, regulated at many levels. This provides support for Waddington’s view of an "epigenetic landscape": successive decisions made by cells over time, which gradually commit cells to their ultimate fate.