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Flylab

Research Interests

• Molecular genetic regulation of early development
• Mechanisms and functions of intracellular RNA localization
• Genetic control of morphogenesis

Research Activities

We are interested in understanding how embryonic cells are instructed to adopt distinct developmental fates, ultimately specifying a complex, three-dimensional organism. Our research program is sub-divided into two projects that utilize Drosophila as a molecular genetic model.

One focus is on how certain classes of mRNAs are localized within the cytoplasm of cells, with an emphasis on the egg and early embryo. Intra-cellular transcript localization is a fundamental mechanism by which informational asymmetries are established in cells. Several years ago we discovered a novel transcript localization mechanism that converts a generally distributed transcript into a localized one by a combination of generalized degradation and localized protection of the RNA. We are currently taking a combined genetic and biochemical approach to defining the cis-acting elements, trans-acting factors and genetic pathways that control this localization process. In addition we are carrying out genome-wide gene expression profiling analyses aimed at identifying all stable versus unstable maternal RNAs in the early embryo, including which of the latter are localized.

Our second research project studies the genetic control of morphogenesis. In particular, we have studied the coordinate cell shape changes and cell rearrangements that convert two-dimensional sheets of cells into three-dimensional structures during embryogenesis. Our analyses have led to insights into how spatial control of particular signal transduction pathways (e.g. the Jun kinase pathway) may be used to regulate the initiation and termination of cell movements. Our studies have also begun to elucidate a novel genetic pathway that controls tissue integrity as cells within epithelia are reorganized. Genetic screens and live imaging of subcellular structures during cell movements are being used to understand the cellular and molecular mechanisms of morphogenesis. These have led to elucidation of the role of cell surface molecules (e.g., integrins, basigin) in promoting morphogenesis and preventing a process known as anoikis (epithelial disintegration and death upon loss of contact with extracellular matrix). These findings are relevant, not only to normal development, but also to understanding the mechanisms of wound healing and cancer.

Future Research Interests

Ongoing analyses of intracellular mRNA localization mechanisms include definition of the cis-acting sequences and trans-acting factors that function in transcript degradation and protection, gene expression profiling and bioinformatics, as well as studies of the genetic control of transcript localization.

Our analyses of the control of morphogenetic cell shape change and movement will focus on germband retraction, dorsal closure and tracheal development during embryogenesis as well as retinal morphogenesis later in development. Genetic and molecular strategies will be used to define the morphogenetic gene hierarchy, with an emphasis on the control of epithelial movements and tissue integrity.

External Funding

• CIHR
• NCIC
• Canada Research Chairs Program

Achievements

• Society for Developmental Biology, Board of Directors (Canada Representative; 2000 - present)
• Federation of American Societies of Experimental Biology, Research Conference Advisory Committee (2001 - 2003; Chair, 2003)
• Developmental Genetics & Birth Defects Priority and Planning Committee, Institute of Genetics, CIHR (2002 - present)
• Medical Review Committee, The Gairdner Foundation, Toronto (2002 - present)
• Co-Director, Canadian Drosophila Microarray Centre (2000 - present)
• Associate Editor, Zygote (1993 - present)
• Editorial Board, Differentiation (2000 - present)
• Editorial Board, Developmental Dynamics (2004 - present)
• Program Co-chair, 45th Annual Drosophila Research Conference, Washington, DC, March 24-28, 2004

Publications

Semotok JL, Cooperstock RL, Pinder BD, Vari HK, Lipshitz HD, Smibert CA. (2005) Smaug recruits the CCR4/POP2/Not deadenylase complex to trigger maternal transcript localization in the early Drosophila embryo. Current Biology 15, 284-294.

Tadros W, Lipshitz HD. (2005) Setting the stage for development: mRNA translation and stability during oocyte maturation and egg activation in Drosophila. Developmental Dynamics 232, 593-608.

Lipshitz HD. (2004) From fruit flies to fallout: Ed Lewis and his science. J. Genetics 83, 201-218.(Reprinted in: Developmental Dynamics 232, 529-546; 2005)

Wilk R, Pickup AT, Hamilton JK, Reed BH, Lipshitz HD. (2004) Dose-sensitive autosomal modifiers identify candidate genes for tissue autonomous and tissue non-autonomous regulation by the Drosophila nuclear zinc-finger protein, Hindsight. Genetics 168, 281-300.

Reed BH, Wilk R, Lipshitz HD. (2004) Integrin-dependent apposition of Drosophila extraembryonic membranes promotes morphogenesis and prevents anoikis. Current Biology 14, 372-380.
(featured article; for commentary see: http://www.f1000biology.com/article/15028211/evaluation)

Wilk R, Pickup AT, Lipshitz HD. (2004) Epithelial morphogenesis. In: Encyclopedia of Molecular Cell Biology & Molecular Medicine, Vol. 4 (2nd Edition). Pp. 277-304 (Ed: R.A. Myers). Wiley-VCH, Weinheim, Germany.

Lipshitz HD. (2004) "Genes, Development & Cancer: The Life and Work of Edward B. Lewis", Springer/Kluwer Academic Publishers, Boston, Massachusetts. (ISBN-4020-7591-X; 576 pp.)

Tadros W, Houston SA, Bashirullah A, Cooperstock RL, Semotok JL, Reed BH, Lipshitz HD. (2003) Regulation of maternal transcript destabilization during egg activation in Drosophila. Genetics 164, 989-1001.

Pickup AT, Lamka ML, Sun Q, Yip MLR, Lipshitz HD. (2002) Control of photoreceptor cell morphology, planar polarity and epithelial integrity during Drosophila eye development. Development 129, 2247-2258.

Reed BA, Wilk R, Lipshitz HD. (2001) Downregulation of Jun kinase signaling in the amnioserosa is essential for dorsal closure of the Drosophila embryo. Current Biology 11, 1098-1108.
(Commentary on this paper is in the Highlights section of Nature Reviews Molecular Cell Biology 2001 2: 641 as well as in the Dispatches section of Current Biology 2001 11:R705-R707)