Hox genes are an ancient family of developmental regulators that help pattern the anterior-posterior axis of animal embryos. The understanding of how HOX proteins function is crucial to an understanding of how animal bodies, including the human body, develop normal morphology during embryonic development. We are fascinated by a number of questions about how Hox genes help shape embryos. One question is based on recent work showing that a microRNA gene called mir-10 is a conserved resident of Hox gene clusters in both Drosophila and mammals. We have found that Drosophila mir-10 is expressed in a pattern that resembles Hox genes and has predicted target sites in Hox messenger RNAs. We plan to isolate mutations that abolish mir-10 functions, and study the interaction between mir-10 and Hox genes in the construction of the Drosophila body plan. We also plan to develop a method to colocalize microRNAs and their target messenger RNAs in processing bodies of developing animal cells. Lessons that we learn from such studies will be applicable to how mir-10 functions in the context of developing mammalian embryos and may provide a new and rapid way of testing the physiological relevance of predicted microRNA/messenger RNA interactions. We are also interested in the functions of HOX protein domains that are conserved between Drosophila and mammals. One such domain is the N-terminal SSYF domain. Recent research indicates that this motif is the core of a HOX transactivation domain, and we will perform protein-protein interaction assays and gene interaction assays to characterize the proteins that bind and potentiate Hox transactivation function in embryos. Finally, although there are isolated cases in which HOX protein functional changes correlate with changes in animal morphology, we are interested in testing whether this is a more widespread phenomenon. So we will test whether changes in HOX protein function in two different arthropod species, Porcellio scaber and Cupiennius salei, contributed to the evolution of limb number in those two animals. ? ? ?

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Method to Extend Research in Time (MERIT) Award (R37)
Project #
5R37HD028315-17
Application #
7275274
Study Section
Development - 2 Study Section (DEV2)
Program Officer
Coulombe, James N
Project Start
1991-08-09
Project End
2011-06-30
Budget Start
2007-07-01
Budget End
2008-06-30
Support Year
17
Fiscal Year
2007
Total Cost
$299,874
Indirect Cost
Name
University of California San Diego
Department
Biology
Type
Schools of Arts and Sciences
DUNS #
804355790
City
La Jolla
State
CA
Country
United States
Zip Code
92093
Patterson, Rachel A; Juarez, Michelle T; Hermann, Anita et al. (2013) Serine proteolytic pathway activation reveals an expanded ensemble of wound response genes in Drosophila. PLoS One 8:e61773
Juarez, Michelle T; Patterson, Rachel A; Li, Wilson et al. (2013) Microinjection wound assay and in vivo localization of epidermal wound response reporters in Drosophila embryos. J Vis Exp :e50750
Lemons, Derek; Pare, Adam; McGinnis, William (2012) Three Drosophila Hox complex microRNAs do not have major effects on expression of evolutionarily conserved Hox gene targets during embryogenesis. PLoS One 7:e31365
Paré, Adam; Kim, Myungjin; Juarez, Michelle T et al. (2012) The functions of grainy head-like proteins in animals and fungi and the evolution of apical extracellular barriers. PLoS One 7:e36254
McHale, Peter; Mizutani, Claudia M; Kosman, David et al. (2011) Gene length may contribute to graded transcriptional responses in the Drosophila embryo. Dev Biol 360:230-40
Kim, Myungjin; McGinnis, William (2011) Phosphorylation of Grainy head by ERK is essential for wound-dependent regeneration but not for development of an epidermal barrier. Proc Natl Acad Sci U S A 108:650-5
Juarez, Michelle T; Patterson, Rachel A; Sandoval-Guillen, Efren et al. (2011) Duox, Flotillin-2, and Src42A are required to activate or delimit the spread of the transcriptional response to epidermal wounds in Drosophila. PLoS Genet 7:e1002424
Hsia, Cheryl C; Pare, Adam C; Hannon, Michael et al. (2010) Silencing of an abdominal Hox gene during early development is correlated with limb development in a crustacean trunk. Evol Dev 12:131-43
Lemons, Derek; Fritzenwanker, Jens H; Gerhart, John et al. (2010) Co-option of an anteroposterior head axis patterning system for proximodistal patterning of appendages in early bilaterian evolution. Dev Biol 344:358-62
Arvey, Aaron; Hermann, Anita; Hsia, Cheryl C et al. (2010) Minimizing off-target signals in RNA fluorescent in situ hybridization. Nucleic Acids Res 38:e115

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