We are interested in understanding the patterning system that diversifies morphology on the anterior-posterior axis of animal embryos, and how changes in this system drive morphological evolution. The homeotic (Hox) genes, important in the development of normal human form, are key factors in this patterning system, but other homeotic modulator proteins act in parallel and downstream to adjust and realize Hox morphological output. Some of the parallel modulators work by regulating Hox transcriptional activation and repression functions. How does evolution in Hox system components regulate morphological diversity? We will take advantage of the diversity in arthropod appendage number to define molecular changes in homologous Hox proteins and/or Hox-regulated enhancers that control appendage morphological evolution in different taxa. In particular, we will focus on mechanisms underlying the different regulatory effects of orthologous insect and crustacean Hox proteins on appendage-promoting genes. Candidate mechanisms in Hox proteins and Hox modulatory factors that may vary in evolution include DNA binding functions, or transcriptional activation/repression functions. How do do paralogous Hox proteins diversify morphology in different Drosophila segments? We will study whether the head Hox Deformed protein and other Hox proteins directly regulate cell death promoting realizator genes such as reaper. We will also test how Distal-less transcription is differentially regulated in head segments by Deformed and Deformed modulator proteins such as Cap 'n' collar B. Microarray methods will be used to test whether the battery of genes regulated by Deformed is similar to the battery of genes regulated by thoracic and abdominal Hox proteins. Is there a common regulatory code that specifies skeletal development in most animals? We will define and analyze a head skeleton-specific enhancer at the Drosophila Dopa decarboxylase locus. We will test whether this enhancer is regulated by Hox, Spen, Tsh, and Drosophila homologs of mammalian skeletal transcription factors. We will apply microarrays to test whether this combination of transcription factors regulates a common group of """"""""skeletal"""""""" and/or """"""""collagen and cross-linking"""""""" genes in Drosophila and other animals.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
5R01HD028315-15
Application #
6920760
Study Section
Genetics Study Section (GEN)
Program Officer
Coulombe, James N
Project Start
1991-08-09
Project End
2006-07-31
Budget Start
2005-08-01
Budget End
2006-07-31
Support Year
15
Fiscal Year
2005
Total Cost
$462,543
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
Capilla, Amalia; Karachentsev, Dmitry; Patterson, Rachel A et al. (2017) Toll pathway is required for wound-induced expression of barrier repair genes in the Drosophila epidermis. Proc Natl Acad Sci U S A 114:E2682-E2688
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
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
Pare, Adam; Lemons, Derek; Kosman, Dave et al. (2009) Visualization of individual Scr mRNAs during Drosophila embryogenesis yields evidence for transcriptional bursting. Curr Biol 19:2037-42
Tour, Ella; Hittinger, Chris Todd; McGinnis, William (2005) Evolutionarily conserved domains required for activation and repression functions of the Drosophila Hox protein Ultrabithorax. Development 132:5271-81
Mace, Kimberly A; Pearson, Joseph C; McGinnis, William (2005) An epidermal barrier wound repair pathway in Drosophila is mediated by grainy head. Science 308:381-5
Veraksa, A; McGinnis, N; Li, X et al. (2000) Cap 'n' collar B cooperates with a small Maf subunit to specify pharyngeal development and suppress deformed homeotic function in the Drosophila head. Development 127:4023-37
Veraksa, A; Del Campo, M; McGinnis, W (2000) Developmental patterning genes and their conserved functions: from model organisms to humans. Mol Genet Metab 69:85-100
Wiellette, E L; McGinnis, W (1999) Hox genes differentially regulate Serrate to generate segment-specific structures. Development 126:1985-95

Showing the most recent 10 out of 21 publications