Animal development requires the differentiation of the progeny ofa single cell, the zygote, into all of the cell tj^es of the organism. One way that cells distinguish themselves from other cells is through differential 1 expression of transcriptional regulatory proteins. Specific patterns of transcription factor expression in each cell can in turn regulate downstream differentiation decisions. This project focuses on defining how transcription factors pattern the increasingly complex array of cell types during the progression of development. The ultimate goal of this work is to uncover general rules through which interactions between transcription factors, chromatin modifications and other genomic features lead to appropriate regulation of downstream target genes.
We aim to generate a validated cellular resolution regulatory network of early development in the C. elegans embryo by combining genetic perturbation with in vivo resolution expression profiling. In parallel, we will test combinatorial models of transcription factor regulation of cell fate and identify direct functional targets for developmentally active transcription factors by examining the consequences of ectopic expression of each factor. When combined with other types of genomic data currently available, the results ofthese experiments will provide the basis to identify general rules governing the activity of transcription factor binding sites.

Public Health Relevance

Knowledge of how transcription factors act in development can provide information about how the same transcription factors function in cancers or disease when inappropriately activated or inactivated. Furthermore, the rules governing combinatorial transcriptional regulatory logic we aim to discover should apply broadly across biology, including in disease.

National Institute of Health (NIH)
National Institute of General Medical Sciences (NIGMS)
Research Transition Award (R00)
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Special Emphasis Panel (NSS)
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Hoodbhoy, Tanya
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University of Pennsylvania
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Burdick, Joshua; Walton, Travis; Preston, Elicia et al. (2016) Overlapping cell population expression profiling and regulatory inference in C. elegans. BMC Genomics 17:159
Zacharias, Amanda L; Walton, Travis; Preston, Elicia et al. (2015) Quantitative Differences in Nuclear ?-catenin and TCF Pattern Embryonic Cells in C. elegans. PLoS Genet 11:e1005585
Walton, Travis; Preston, Elicia; Nair, Gautham et al. (2015) The Bicoid class homeodomain factors ceh-36/OTX and unc-30/PITX cooperate in C. elegans embryonic progenitor cells to regulate robust development. PLoS Genet 11:e1005003
Churgin, Matthew A; He, Liping; Murray, John I et al. (2014) Construction of a system for single-cell transgene induction in Caenorhabditis elegans using a pulsed infrared laser. Methods 68:431-6
Burdick, Joshua T; Murray, John Isaac (2013) Deconvolution of gene expression from cell populations across the C. elegans lineage. BMC Bioinformatics 14:204
Churgin, Matthew A; He, Liping; Murray, John I et al. (2013) Efficient single-cell transgene induction in Caenorhabditis elegans using a pulsed infrared laser. G3 (Bethesda) 3:1827-32
Richards, Julia L; Zacharias, Amanda L; Walton, Travis et al. (2013) A quantitative model of normal Caenorhabditis elegans embryogenesis and its disruption after stress. Dev Biol 374:12-23
Abdus-Saboor, Ishmail; Stone, Craig E; Murray, John I et al. (2012) The Nkx5/HMX homeodomain protein MLS-2 is required for proper tube cell shape in the C. elegans excretory system. Dev Biol 366:298-307
Murray, John Isaac; Bao, Zhirong (2012) Automated lineage and expression profiling in live Caenorhabditis elegans embryos. Cold Spring Harb Protoc 2012:
Abdus-Saboor, Ishmail; Mancuso, Vincent P; Murray, John I et al. (2011) Notch and Ras promote sequential steps of excretory tube development in C. elegans. Development 138:3545-55

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