................................................................................................................................ v Introduction ........................................................................................................................... 1 Cellular Diversity ........................................................................................................... 1 Neural Diversity and Function ...................................................................................... 3 Biogenesis ...................................................................................................................... 8 Multicellularity and the Origins of Stem Cells ........................................................... 10 Stem Cells .................................................................................................................... 13 Potential .............................................................................................................. 13 Commitment and Plasticity ................................................................................ 15 Lineage Topology .............................................................................................. 16 The Molecular Basis of Cell Diversification ............................................................... 22 The Regulatory Architecture of the Genome .................................................... 23 Transcriptional Regulation of Gene Expression ................................................ 27 Gene Regulatory Networks .................................................................................... 35 Global GRN Dynamics ...................................................................................... 35 GRNs and the Power of Attraction in the Cell State Space .............................. 37 Causes and Consequences of Stochastic Variation in Gene Expression .......... 39 Self-Organiz and Transitions of Cell Identity .............................. 41 Motifs in GRN Circuits ...................................................................................... 43 Hierarchical Organization of GRN Sub-Circuit Outputs .................................. 45 Extrinsic Regulation of GRNs ........................................................................... 47 Morphogenesis and Regulation of Cell Identity Across Tissues ...................... 56 Patterning over Long Distance by Morphogens ................................................ 58 Aims .................................................................................................................................... 71 Results and Discussion ........................................................................................................ 73 Paper I. Mechanistic Differences in the Transcriptional Interpretation of Local and Long-Range Shh Morphogen Signaling ......................................... 73 Paper II. A Homeodomain Feedback Circuit Underlies Step-Function Interpretation of a Shh Morphogen Gradient during Ventral Neural Patterning ............................................................................................... 75 Paper III. Rfx4 Regulates the Local Interpretation of Shh Signaling in the Developing Nervous System ................................................................. 77 Paper IV. A SoxB1-Driven Transcriptional Network Underlies Neural-Specific Interpretation of Morphogen Signals ..................................................... 81 Future Perspectives ............................................................................................................. 83 Acknowledgements ............................................................................................................. 8 References ........................................................................................................................... 8