The long term objective of the Pi's research is to understand how changes in the regulation of developmental processes permit the evolution of changes in body plan. For this purpose, we compare the development of extant organisms with respect to the """"""""tree of life"""""""" (phylogeny) by which they arose. Comparisons between diverse organisms should also help to determine which developmental features discovered in genetic model organisms are more likely to be operating in human, and should shed light on the links between acute perturbations of developmental mechanisms and birth defects. Leeches (segmented worms, phylum Annelida) belong to the super-phylum Lophotrochozoa, one of three groups of bilaterally symmetric animals in the emerging phylogeny based on comparisons of DMA and protein sequences between species. Lophotrochozoa includes roughly half of the extant phyla, including non-acoel flatworms, molluscs and annelids. However, most research in development concerns vertebrates (super-phylum Deuterostomia), nematode orfruitfly (both in the superpylum Ecdysozoa). Including lophotrochozoan species will increase the breadth and power of comparative development. The leech Helobdella is used because its embryo is among the best studied of the many lophotrochozoan species. It also has a compact genome. As a result, along with a polychaete worm (Capitella) and a mollusc (Lottia), Helobdella is one of 3 lophotrochozoans selected for whole genome sequencing by the Dept. of Energy's Joint Genome Institute. Synergistic developmental and genomic analyses within and among these 3 species will help to understand the links between genomic and developmental change. Specifically, the proposed research is to elucidate the role(s) of the TGFb pathway in the early leech embryo, using in situ hybridization and RT-PCR to study gene expression, plus intracellular injection of lineage tracers and mRNAs or anti-sense mopholino oligomers to compare cell fates in normal embryos with those where the TGFb pathways have been disrupted. The proposed experiments will contribute to understanding how TGFb signaling specifies dorsal fates in Drosophila, but ventral fates in vertebrates. They will also contribute to understanding the cellular processes known as epithelial-to-mesenchymal transitions (EMTs), which play a critical role both in normal development and in cancer metastasis.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM074619-03
Application #
7541733
Study Section
Genetic Variation and Evolution Study Section (GVE)
Program Officer
Haynes, Susan R
Project Start
2007-01-01
Project End
2010-12-31
Budget Start
2009-01-01
Budget End
2009-12-31
Support Year
3
Fiscal Year
2009
Total Cost
$279,033
Indirect Cost
Name
University of California Berkeley
Department
Biochemistry
Type
Schools of Arts and Sciences
DUNS #
124726725
City
Berkeley
State
CA
Country
United States
Zip Code
94704
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Weisblat, David A; Kuo, Dian-Han (2014) Developmental biology of the leech Helobdella. Int J Dev Biol 58:429-43
Cho, Sung-Jin; Vallès, Yvonne; Weisblat, David A (2014) Differential expression of conserved germ line markers and delayed segregation of male and female primordial germ cells in a hermaphrodite, the leech helobdella. Mol Biol Evol 31:341-54
Simakov, Oleg; Marletaz, Ferdinand; Cho, Sung-Jin et al. (2013) Insights into bilaterian evolution from three spiralian genomes. Nature 493:526-31
Kuo, Dian-Han; Shankland, Marty; Weisblat, David A (2012) Regional differences in BMP-dependence of dorsoventral patterning in the leech Helobdella. Dev Biol 368:86-94
Kuo, Dian-Han; Weisblat, David A (2011) Intermediate filament genes as differentiation markers in the leech Helobdella. Dev Genes Evol 221:225-40
Kuo, Dian-Han; Weisblat, David A (2011) A new molecular logic for BMP-mediated dorsoventral patterning in the leech Helobdella. Curr Biol 21:1282-8
Cho, Sung-Jin; Valles, Yvonne; Giani Jr, Vincent C et al. (2010) Evolutionary dynamics of the wnt gene family: a lophotrochozoan perspective. Mol Biol Evol 27:1645-58
Lyons, Deirdre C; Weisblat, David A (2009) D quadrant specification in the leech Helobdella: actomyosin contractility controls the unequal cleavage of the CD blastomere. Dev Biol 334:46-58
Gline, Stephanie E; Kuo, Dian-Han; Stolfi, Alberto et al. (2009) High resolution cell lineage tracing reveals developmental variability in leech. Dev Dyn 238:3139-51