The C. elegans Hox gene lin-39 encodes a homeodomain-containing protein similar to the Drosophila Deformed and Sex Combs Reduced proteins, lin-39 is expressed in the C. elegans mid-body region, including the vulval precursor cells, and is required for the proper fate determination of these cells. In these vulval precursor cells, the tin-39 gone is coordinately regulated by both Wnt and Ras signaling pathways. We propose that the Hox gene lin-39 in C. elegans functions as a transcriptional regulator that controls the expression of a set of downstream genes in order to control the fates of the vulval precursor cells. We propose experiments to 1) determine how the Wnt and Ras pathways regulate LIN-39 protein levels, 2) identify LIN-39 binding sites in vitro and assay their relevance in vivo, 3) determine whether phosphorylation alters the functions of LIN-39 in vitro or in vivo, and 4) identify and characterize target genes regulated by L1N-39 using a microarray -based approach. Hox proteins such as LIN-39 are known to function in the patterning of cells along the anterior-posterior axis during the development of all metazoans, and defects in Hox gone expression can lead to drastic defects in development. Although Hox proteins have been characterized in many species, only a handful of target genes have been identified for these proteins. Therefore much can be learned about the function of this important class of master developmental control genes in all organisms, including humans, by the characterization of Hox protein targets in the model system C. elegans, for which full genomic sequence is available and functional genomic approaches are available.

National Institute of Health (NIH)
National Institute of General Medical Sciences (NIGMS)
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Genetics Study Section (GEN)
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Haynes, Susan R
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University of Maryland Balt CO Campus
Schools of Arts and Sciences
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Gorrepati, Lakshmi; Krause, Michael W; Chen, Weiping et al. (2015) Identification of Wnt Pathway Target Genes Regulating the Division and Differentiation of Larval Seam Cells and Vulval Precursor Cells in Caenorhabditis elegans. G3 (Bethesda) 5:1551-66
Liu, Wan-Ju; Reece-Hoyes, John S; Walhout, Albertha J M et al. (2014) Multiple transcription factors directly regulate Hox gene lin-39 expression in ventral hypodermal cells of the C. elegans embryo and larva, including the hypodermal fate regulators LIN-26 and ELT-6. BMC Dev Biol 14:17
Jackson, Belinda M; Abete-Luzi, Patricia; Krause, Michael W et al. (2014) Use of an activated beta-catenin to identify Wnt pathway target genes in caenorhabditis elegans, including a subset of collagen genes expressed in late larval development. G3 (Bethesda) 4:733-47
Gorrepati, Lakshmi; Thompson, Kenneth W; Eisenmann, David M (2013) C. elegans GATA factors EGL-18 and ELT-6 function downstream of Wnt signaling to maintain the progenitor fate during larval asymmetric divisions of the seam cells. Development 140:2093-102
Gleason, Julie E; Eisenmann, David M (2010) Wnt signaling controls the stem cell-like asymmetric division of the epithelial seam cells during C. elegans larval development. Dev Biol 348:58-66
Gleason, Julie E; Szyleyko, Elizabeth A; Eisenmann, David M (2006) Multiple redundant Wnt signaling components function in two processes during C. elegans vulval development. Dev Biol 298:442-57
Wagmaister, Javier A; Gleason, Julie E; Eisenmann, David M (2006) Transcriptional upregulation of the C. elegans Hox gene lin-39 during vulval cell fate specification. Mech Dev 123:135-50
Wagmaister, Javier A; Miley, Ginger R; Morris, Corey A et al. (2006) Identification of cis-regulatory elements from the C. elegans Hox gene lin-39 required for embryonic expression and for regulation by the transcription factors LIN-1, LIN-31 and LIN-39. Dev Biol 297:550-65
Eisenmann, David M (2005) Wnt signaling. WormBook :1-17