Faculty and Research
Faculty by Name
David Weisblat
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David Weisblat
Professor of Cell and Developmental Biology*
*And Affiliate, Division of Neurobiology
Research Interests
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Molecular phylogenies indicate that most bilaterally symmetric animals fall into three major groups, whose ancestors had already diverged by the time of the Cambrian explosion, ~600 million years ago: Deuterostomia (echinoderms, hemichordates and chordates); Edysozoa (arthropods, nematodes and other "cuticle-shedding" animals); and Lophotrochozoa (annelids, mollusks, non-acoel flatworms, and a number of related minor phyla). Comparing modern representatives of all three of these groups is essential to understanding how changes in developmental processes have enabled the evolution of diverse body plans, but most developmental analyses have focused on a few model systems within Ecdysozoa and Deuterostomia. Leeches (phylum Annnelida, segmented worms) are regarded by some with a repugnance so intense as to preclude their consideration as objects for biological investigation. But in fact glossiphoniid leech embryos are quite beautiful and are well suited for cellular and molecular analyses of embryonic development. Thus, they are among the best studied representatives of the Lophotrochozoa.
The goals of the research in our lab are twofold: first, to obtain as satisfying as possible an understanding of leech development; and second, to understand how developmental processes are modified during the evolution of different animal taxa. For example, leeches undergo spiral cleavages homologous to those of mollusks, yet generate a segmented body plan, like arthropods. How have cell fates been modified among the different spirally cleaving animal groups to generate different types of embryos and adults? In particular, how is it that leeches make exactly 32 segments during development and cannot make more, either post-embryonically or in response to injury, while closely related annelids (oligochaetes) exhibit wonderful capacities for post-embryonic segmentation, regeneration, and even vegetative reproduction? And finally, what can we conclude from the similarities and differences among annelid, arthropod and vertebrate systems about the evolutionary origin(s) of segmentation?
Our relatively detailed understanding of Helobdella development compared to other "non-model" organisms has led to its selection as among the first lophotrochozoan species for BAC library construction (at CHORI in Oakland with NSF support) and genome sequencing (by the JGI in Walnut Creek with support from DOE). Assembly of the genomic sequence is under way and a database of ~140,000 ESTs is available to aid in annotation. In addition to adding an important new reference point for comparative genomics, these resources are greatly accelerating our ongoing studies of Helobdella development.
Current Projects
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Two areas of primary interest at present are:
(1) the deployment, function and interconnection of intercellular signaling pathways (WNT, NOTCH, TGFbeta and MAPK) in the early embryo, including dynamic gene expression in the 2-cell embryo and the assignment of distinct mesodermal and ectodermal fates to two sister cells at 4th cleavage;
(2) the molecular control of stem cell divisions in segmentation, especially a "grandparental" mode of stem cell division that generates two distinct cell types in exact alternation.Other areas of interest include:
(1) the inductive regulation of cell-cell fusion in endoderm;
(2) the mechanisms of epiboly (cell movements during gastrulation);
(3) gangliogenesis and the assignments of specific neuronal fates.Our work entails the use of various cellular, molecular and embryological techniques. Microinjection of cell lineage tracers and various imaging techniques are frequently used in combination with other procedures. In particular, injection of synthetic mRNAs or antisense morpholino oligonucleotides into selected cells allows us to express markers and/or perturb gene expression in specific parts of the embryo. We are particularly excited at the prospects of combining genomic and embryological approaches.
Selected Publications
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MAPK regulation of maternal and zygotic Notch transcript stability in early development. [F.C.Gonsalves and D.A. Weisblat (2007) PNAS 104, 531-536]
Maternal expression of a NANOS homolog is required for early development of the leech Helobdella robusta. [S.J. Agee, D.C. Lyons and D.A. Weisblat (2006) Developmental Biology 298, 1-11]
Asymmetrization of first cleavage by transient disassembly of one spindle pole aster, in the leech Helobdella robusta, [X. Ren and D.A. Weisblat (2006) Developmental Biology 292, 103-115]
Characterization of Notch-class gene expression in segmentation stem cells and segment founder cells in Helobdella robusta (Lophotrochozoa; Annelida; Clitellata; Hirudinida; Glossiphoniidae). [A.S. Rivera, F.C. Gonsalves, M.H. Song, B.J. Norris and D.A. Weisblat (2005) Evolution & Development 7, 588-599]
Applications of mRNA injections for analyzing cell lineage and asymmetric cell divisions during segmentation in the leech Helobdella robusta, [S.O. Zhang and D.A. Weisblat (2005) Development 132, 2103-2113]
Cell interactions that affect axonogenesis in the leech, Theromyzon rude. [D.H. Shain, D.K. Stuart, F.Z. Huang, and D.A. Weisblat (2004) Development 131, 4143-4153]
Cell cycle-dependent expression of a hairy and Enhancer of split (hes) homolog during cleavage and segmentation in leec embryos. [M.H. Song, F.Z. Huang, F.C. Gonsalves and D.A. Weisblat (2004) Developmental Biology 269, 183-195]
A hedgehog homolog regulates gut formation in leech (Helobdella). [D. Kang, F.Z. Huang, D. Li, M. Shankland, W. Gaffield and D.A. Weisblat (2003) Development 130, 1645-1657]
Expression and function of an even-skipped homolog in the leech Helobdella robusta. [M.H. Song, F.Z. Huang, G.Y. Chang and D.A. Weisblat (2002) Development 129,3681-3692]
Maternal and zygotic expression of a nanos-class gene in the leech Helobdella robusta: primordial germ cells arise from segmental mesoderm. [D. Kang, M. Pilon and D.A. Weisblat (2002) Developmental Biology 245, 28-41]
Micromere lineages in the glossiphoniid leech. [F.Z. Huang, D. Kang, F. Ramirez-Weber, S.T. Bissen and D.A. Weisblat (2002) Development 129, 719-732]
Last Updated 2007-02-14