Wendy Hanna-Rose Assistant Professor of Biochemistry and Molecular Biology 104D Life Sciences Building, University Park, PA 16802 Phone: (814) 865-7904 Fax: (814) 863-7024 E-mail: wxh21@psu.edu B.A. in Biology , Anderson University Ph.D. in Microbiology & Molecular Genetics, Harvard University Postdoctoral, Molecular, Cellular & Developmental Biology, University of Colorado, Boulder Hanna-Rose Lab Web Site

Developmental genetics of organogenesis and morphogenesis in C. elegans

During animal development, groups of cells of various identities must coordinate their movements, interactions and morphogenesis in order to organize themselves into functional structures called organs. Furthermore, the development of functional organ systems requires strict coordination of the spatial development among organs. The overarching goals of the Hanna-Rose lab are to elucidate fundamental mechanisms of how cell morphology is genetically programmed and controlled, resulting in the accurate development of organs from unorganized groups of specified cells, and how organogenesis is coordinated among different organs in functional organ systems. We study development of the hermaphrodite egg-laying apparatus and the male mating apparatus in the nematode Caenorhabditis elegans as models to address questions of how organogenesis is genetically controlled and executed. We hypothesize that the molecular mechanisms employed by morphogenesis regulators and effectors in C. elegans are conserved in humans and that our analysis of how C. elegans organogenesis can go awry will lend insight into the causes of structural birth defects in humans.

Research Projects

1. The vulva-uterine connection

The C. elegans egg-laying apparatus consists of the uterus and the tubular vulva, which provides a passage for eggs to exit the vulva during egg laying, as well as their associated muscles and neurons. Formation of the connection between the independently formed lumens of the vulva and the uterus provides a powerful model to study organogenesis. Morphogenesis of both the uterus and the vulva is observable in live animals and the anatomy is relatively simple (Fig. 1).

Morphogenesis is also sufficiently complex to reveal mechanisms controlling diverse cellular processes such as how and when cells divide, change shape, migrate and fuse. We study three different genes that play a role in ensuring a proper connection between the uterus and the vulva (Fig. 2).

EGL-26 encodes a putative palmitolytransferase that controls morphogenesis of the vulval cell called vulF, which directly interacts with the overlying uterus (Estes et al 2007).

COG-3 promotes proper temporal coordination of vulval and uterine development and appears to either directly or indirectly perturb EGF signaling between the vulva and the uterus (Huang and Hanna-Rose 2006).

EGL-13 encodes a Sox domain transcription factor that acts in the uterine seam cell to maintain or fully execute cell fate, indirectly affecting fusion of the anchor cell and the uterine seam cell (Hanna-Rose and Han 1999). We have identified putative targets of this transcription factor and are studying its function.

2. Development and function of the male mating apparatus.

We are expanding our research into another tractable system for probing the development of organs by analyzing the role of the cog-3 gene in male development. About 30% of cog-3 males have spicules that are crumpled. Spicules are prong-like organs that are inserted into the hermaphrodite vulva during mating. Spicule fate specification also requires an EGF signal, and increases or decreases in this pathway can result in crumpled spicules. Characterization of cog-3 in males will more clearly define the interactions of this gene with the EGF pathway.

3. Gene Regulation in C. elegans

We have found that mutations in the him-8 gene suppress egl-13 mutants. him-8 was originally identified due to its role in promoting proper segregation of the sex chromosomes during meiosis. We have demonstrated that HIM-8 plays a role in the soma in regulating the activity of a variety of genes (Nelms and Hanna-Rose 2006 and Nelms et al 2007). HIM-8 is a zinc finger protein and is encoded with three related proteins called ZIM-1, ZIM-2 and ZIM-3 in a C. elegans operon. These related ZIM proteins appear to function similarly to HIM-8 in the soma, and we are actively pursuing experiments to determine the mechanism whereby this novel family of genes regulate somatic gene activity.

Representative Publications:

• Kathleen A. Estes, Rasika Kalamegham, and Wendy Hanna-Rose (2007). Membrane localization of the NlpC/P60 family protein EGL-26 correlates with regulation of vulval cell morphogenesis in C. elegans . Developmental Biology, in press doi:10.1016/j.ydbio.2007.05.020.
• Hongliu Sun, Brian L. Nelms, Sama F. Sleiman, Helen M. Chamberlin and Wendy Hanna-Rose. (2007) Genetic suppression in C. elegans by HIM-8 and related C2H2 zinc finger proteins. Genetics, in press.

• Li Huang and Wendy Hanna-Rose. (2006) EGF signaling overcomes a uterine cell death associated with
  temporal mis-coordination of organogenesis within the C. elegans egg-laying apparatus. Developmental Biology 300(2):599-611.

• Brian Nelms and Wendy Hanna-Rose. (2006) C. elegans HIM-8 has a meiosis-independent function in antagonizing the activity of the EGL-13 Sox protein. Developmental Biology 293(2): 392-402.
• Wendy Hanna-Rose and Min Han. (2002) The Caenorhabditis elegans EGL-26 protein mediates vulval cell morphogenesis. Developmental Biology 241(2):247-258.
• Kelly Grant, Wendy Hanna-Rose and Min Han. (2000) sem-4 Promotes Vulval Cell-Fate Determination in Caenorhabditis elegans through Regulation of lin-39 Hox. Developmental Biology 223: 496-506.
• Wendy Hanna-Rose and Min Han. (1999) COG-2, a Sox domain protein necessary for establishing a functional vulval-uterine connection in Caenorhabditis elegans. Development 126(1): 169-179.

   

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