Homeobox genes are an ancient family of developmental regulators that pattern animal embryos. We are fascinated by the genetic circuitry involving homeobox genes that assigns developmental fates to different cells in embryos, and how the redeployment of such circuits has helped to evolve morphological diversity during animal evolution.
One aim i s to test the idea that a function of microRNAs is to dampen the deleterious effects of sporadic transcription of developmental regulatory genes, such as those of the homeobox family. Another aim is based on our finding that genes of the core proximodistal appendage- patterning network of arthropods are expressed in the anterior neuroectoderm of Drosophila embryos, as well as in the anterior neuroectoderm of chordate embryos in an overlapping anteroposterior order. These genes encode the transcription factors Distal-less, apterous, dachshund, hemothorax, and buttonhead/Sp8. These results, in concert with existing expression data from a variety of other animals, including mammals, suggest that a pre-existing gene network for anterior head patterning, which eventually results in different regional specializations of the brain, was co-opted to pattern the proximodistal axis of bilateral appendages in animals. This model needs more experimental tests, and such tests are outlined in this proposal. These include testing for conserved cross-regulatory relationships among these genes in the anterior neuroectoderm of Drosophila embryos, and testing whether the same set of genes are expressed in the heads of animals that represent the common ancestors of present day arthropods and vertebrates. If validated, this model would represent an amazing example of how a gene network has been redeployed to innovate new morphological features in animal body plans. Another aim is to use high resolution in situ hybridization to study how certain homeobox genes are transcriptionally activated by long-range DNA enhancers at the level of individual genes in individual embryonic nuclei.

Public Health Relevance

(See Instructions): This research will teach us more about how environmental influences alter activities of developmental control genes, which may underlie sporadic birth defects. This research will also increase our knowledge of the genetic circuitry that controls which cells in the developing head of embryos become different regions of the brain.

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 #
5R37HD028315-22
Application #
8258217
Study Section
Special Emphasis Panel (NSS)
Program Officer
Coulombe, James N
Project Start
1991-08-09
Project End
2016-06-30
Budget Start
2012-07-01
Budget End
2013-06-30
Support Year
22
Fiscal Year
2012
Total Cost
$289,306
Indirect Cost
$98,056
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
Pare, 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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