title: The Regulatory Landscape of Lineage Differentiation in a Metazoan Embryo.
abstract: Elucidating the mechanism of cell lineage differentiation is critical for our understanding of development and fate manipulation. Here we combined systematic perturbation and direct lineaging to map the regulatory landscape of lineage differentiation in early C. elegans embryogenesis. High-dimensional phenotypic analysis of 204 essential genes in 1,368 embryos revealed that cell lineage differentiation follows a canalized landscape with barriers shaped by lineage distance and genetic robustness. We assigned function to 201 genes in regulating lineage differentiation, including 175 switches of binary fate choices. We generated a multiscale model that connects gene networks and cells to the experimentally mapped landscape. Simulations showed that the landscape topology determines the propensity of differentiation and regulatory complexity. Furthermore, the model allowed us to identify the chromatin assembly complex CAF-1 as a context-specific repressor of Notch signaling. Our study presents a systematic survey of the regulatory landscape of lineage differentiation of a metazoan embryo.
authors: Sloan Kettering Institute, 1275 York Avenue, New York, NY 10065, USA. Electronic address: zdu@genetics.ac.cn.
authors: Zhuo
authors: Z
authors: Du
authors: Sloan Kettering Institute, 1275 York Avenue, New York, NY 10065, USA.
authors: Anthony
authors: A
authors: Santella
authors: Sloan Kettering Institute, 1275 York Avenue, New York, NY 10065, USA.
authors: Fei
authors: F
authors: He
authors: Sloan Kettering Institute, 1275 York Avenue, New York, NY 10065, USA.
authors: Pavak K
authors: PK
authors: Shah
authors: Sloan Kettering Institute, 1275 York Avenue, New York, NY 10065, USA.
authors: Yuko
authors: Y
authors: Kamikawa
authors: Sloan Kettering Institute, 1275 York Avenue, New York, NY 10065, USA. Electronic address: baoz@mskcc.org.
authors: Zhirong
authors: Z
authors: Bao
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000166:cytology / Q000196:embryology* / Q000378:metabolism; D029742:Caenorhabditis elegans Proteins / Q000378:metabolism*; D002454:Cell Differentiation / Q000235:genetics*; D019070:Cell Lineage / Q000235:genetics*; D047108:Embryonic Development / Q000235:genetics; D018507:Gene Expression Regulation, Developmental / Q000235:genetics*; D053263:Gene Regulatory Networks / Q000235:genetics*; D008954:Models, Biological; D015398:Signal Transduction / Q000235:genetics
chemical_list: D029742:Caenorhabditis elegans Proteins