[P1.82]: Histone H3 lysine 27 trymethylation plays a key role in bmp dependent dorsal spinal cord development

nesis. Five Notch ligands (delta 1, 3, 4 and Jagged 1, 2) are expressed in the vertebrate nervous system and each ligand exhibits a different spatial and temporal pattern, suggesting that they may play distinct roles. In this work, we aim to unravel the function of three ligands (Dll1, Dll4 and Jag1) during the development of the embryonic spinal cord, where Dll1 and Jag1 show a complementary expression pattern along the DV axis, while Dll1 and Dll4 show sequential expression in the pV2 domain. Through the analysis of conditional knockout mice for Dll1 and Jag1, we show that both ligands can activate Notch signalling within their specific domains of expression. However, while Dll1 seems to signal also to Jag1expressing domains, Jag1 is unable to signal to the neighbouring. Dll1-expressing domains. Loss of Dll1 or Jag1 leads to domainspecific increase of neuronal differentiation but neither Dll1 nor Jag1 appears to be involved in creating cell diversity. Thus, extrinsic signalling mediated by either Dll1 or Jag1 is likely to be mainly used to maintain a pool of progenitor cells. The situation is different in the pV2 domain of the spinal cord, where both Dll1 and Dll4 are expressed. In this domain, V2a and V2b interneurons are generated at the same time from neuroepithelial progenitors. In the absence of Dll4 function, no V2b cells are specified, while Dll1 seems to have no impact in this cell fate decision. A different regulatory circuitry is, therefore, required to control neuronal diversification in this domain. Our work supports the view that the use of different Notch ligands is a key feature for the tight control of neurogenesis: when only one ligand is expressed, it functions to ensure the balance between progenitor and differentiated cells; when two ligands are expressed, then one functions to specify interneuron subtype identity in a uniform population of ventral progenitors.