Zheng Zhou

Molecular genetic studies of clearance of apoptotic cells in C. elegans

During an animal's development and adulthood many unwanted cells are eliminated by a process called "programmed cell death" or "apoptosis". Such cells undergo specific changes in appearance, die, and are quickly engulfed and digested by other cells. The engulfment step is important because dead cells can contain material that, if released, could harm neighboring cells. Both inefficient engulfment of apoptotic cells and incorrect engulfment of cells that should normally live could result in human diseases. The engulfment process utilizes mechanisms that remain largely unknown to regulate cell-cell signaling, cell-cell interaction, and cytoskeletal reorganization. These mechanisms are likely to be utilized by many other biological processes such as cell migration. Therefore, understanding the mechanisms that control engulfment has important meanings to biological and medical research.

My laboratory is investigating how engulfment of apoptotic cells is controlled. We are working to answer the following questions:

1. How do engulfing cells recognize the apoptotic cells, their specific targets? What is the molecular nature of the "eat me" signal(s) presented by the apoptotic cells?
   
   
2. What are the signaling pathways that trigger and regulate the polarized extension of engulfing cell surfaces that embrace the apoptotic cells? How are the plasma membrane and the actin cytoskeleton underneath it rearranged during cell-surface extension?
   
   
3. How is an apoptotic cell efficiently degraded inside the engulfing cell?
   
   

We are studying these questions using a small round worm, the nematode Caenorhabditis elegans, a simple organism in which apoptotic cells are easily recognizable and genetic manipulations are well-established. Because many genes that have been identified in C. elegans resemble genes that perform analogous functions in humans, it is likely that what is learned from studying this worm will enhance the understanding of how human genes work. In C. elegans, apoptotic cells are rapidly engulfed and digested by their neighboring, living cells. Previous genetic analyses have identified six genes that control engulfment by acting in two partially redundant pathways: ced-1, -6, -7 in one, and ced-2, -5, and -10 in the other (ced: cell death abnormal). Mutations in these genes result in defects in the engulfment of apoptotic cells and persistent "cell corpses" remain in the worm's body.

Selected Publications

Chen F, Hersh BM, Conradt B, Zhou Z, Riemer D, Gruenbaum Y, Horvitz HR (2000) Translocation of C. elegans CED-4 to nuclear membranes during programmed cell death. Science 287:1485-1489.

Zhou Z, Hartwieg E, Horvitz HR (2001) CED-1 is a transmembrane receptor that mediates cell corpse engulfment in C. elegans. Cell 104:43-56.

Zhou Z, Caron E, Hartwieg E, Hall A, Horvitz HR (2001) The C. elegans PH domain protein CED-12 regulates cytoskeletal reorganization via a Rho/Rac GTPase signaling pathway. Developmental Cell 1:477-489.

Mangahas PM, Zhou Z (2005) Clearance of apoptotic cells in Caenorhabditis elegans. Seminars in Cell and Developmental Biology 16:295-306.

Yu X, Odera S, Chuang CH, Lu N, Zhou Z (2006) C. elegans Dynamin mediates the signaling of phagocytic receptor CED-1 for the engulfment and degradation of apoptotic cells. Developmental Cell 10:743-757.

Venegas V, Zhou Z (2007) Two alternative mechanisms that regulate the presentation of apoptotic cell engulfment signal in Caenorhabditis elegans. Molecular Biology of the Cell 18:3180-3192.

Contact Information

Zheng Zhou, Ph.D.

Department of Biochemistry and Molecular Biology

Baylor College of Medicine

One Baylor Plaza 322B

Houston, Texas 77030, U.S.A.

Tel: (713) 798-6489

Fax: (713) 798-9438

E-mail: zhengz@bcm.edu