Homeobox Gene Silencing During Organogenesis

Cold Spring Harbor Laboratory, Cold Spg Hbr NY

Investigators

Abstract

Stem cells are responsible for the development of all tissues and organs. Plant stem cells are located in meristems, the specialized growing tips of the plant. Indeterminate growth of the shoot apical meristem (SAM) results in part from the activity of the knox homeobox genes. Down-regulation of knox expression is a key step in the formation of differentiating lateral organs, such as leaves. Moreover, establishment of determinacy in developing organs requires the continued silencing of the knox genes. Defects in this process lead to the uncontrolled proliferation of cells and developmental abnormalities. The establishment of determinacy involves the MYB domain protein ASYMMETRIC LEAVES1 (AS1). This protein is part of a type of "memory" system that keeps the knox genes stably silenced through the many rounds of cell division required for organogenesis. This project will elucidate the molecular mechanism by which AS1 represses knox expression. The proteins and cis-acting DNA elements involved in targeting the AS1 repressor complex to the knox loci will be determined, and the role of previously identified knox antisense transcripts in this process will be established. Gene silencing usually involves epigenetic modifications such as the methylation of critical DNA sequences or the histone proteins associated with DNA. The nature of the epigenetic modifications that maintain knox gene silencing and establish determinacy will be elucidated. This research can reveal a crucial mechanistic step of RNA-directed gene silencing and will provide insight into a novel memory system important for developmental gene regulation. The key components of this memory system are found in both plants and animals. This research can thus improve our understanding of stem cell function in animals as well as plants. This project will also make significant educational contributions through the training of a postdoctoral fellow and a graduate student. In addition, one undergraduate student will be selected each summer to work on aspects of this project, and through a partnership program with Locust Valley H. S. in New York, this research program provides research opportunities for selected high school students with a strong interest in the Biological Sciences.