The Wightman laboratory at Muhlenberg College is studying the mechanisms by which genes direct the formation of organs during animal development. One gene, called tailless plays an important role in directing how the uterus of the microscopic nematode worm Caenorhabditis elegans forms. The lab uses molecular, biochemical and genetic strategies to learn how this gene is controlled by other genes and how it, in turn, controls still other genes. The outcome is a better understanding of the molecular pathway - the series of specific steps - that allows cells to communicate with each other during development to create organized tissues and organs. The tailless gene also exists in vertebrates, including humans, where it functions in the development of stems cells in the brain. Therefore, an understanding of how the nematode tailless gene works helps illuminate the equivalent pathways in other animals. The Wightman laboratory consists of two professional scientists and six to twelve undergraduate students. Therefore, a major impact of this work is to advance education. Students who learn science by participating in scientific research learn more and are well-prepared for careers in science and the clinical professions.
The Wightman laboratory at Muhlenberg College is studying the mechanisms by which genes direct the formation of organs during animal development. One gene, called tailless (or nhr-67), plays an important role in directing how the uterus of the microscopic nematode worm Caenorhabditis elegans forms. The lab uses molecular, biochemical, and genetic strategies to learn how the product of this gene, the NHR-67 protein, is controlled by other genes and how it, in turn, controls still other genes. The outcome is a better understanding of the molecular "pathway"—the series of specific steps—that allow cells to communicate with each other during development in order to create organized tissues and organs. The tailless gene also exists in vertebrates, including humans, where it functions in the development of stems cells in the brain. Therefore, an understanding of how nematode NHR-67 works helps illuminate the equivalent pathways in other animals. The complete project identified two proteins-- transcription factors-- called HLH-2 and SEX-1 as regulators that bind to DNA upstream of the nhr-67 gene and function to switch on the gene in cells that will create the uterus of the worm. A third protein, called NOTCH, may also function in this process. Five other proteins were also identified as tenative regulators. This accomplishment defined six specific pieces of DNA that are responsible for directing the expression of nhr-67 in the developing uterus. The Wightman lab also discovered that NHR-67 itself is responsible for turning on other genes with known roles in the development of the uterus. In one cell, called the anchor cell, we identified three important genes that NHR-67 switches on, including LAG-2, a gene that produces a chemical signal. In a different group of cells, called VU cells, NHR-67 switches on a different gene that encodes the cell surface receptor molecule that is used for chemical communication between the developing anchor cell and VU cells. Therefore, NHR-67 coordinates the expression of key signals in the signaling cell and the corresponding receptor for the signal in the responding cell. This chemical signaling pathway, called the NOTCH pathway, is an important regulator of cells and development in vertebrates including humans. The Wightman laboratory consists of two professional scientists and six to twelve undergraduate students at any one time. Therefore, a major impact of this work is to advance science education. Students who learn science by participating in scientific research learn more and are well-prepared for careers in science and the clinical professions. Student researchers supported by this project have gone on to advanced study in elite Ph.D. and M.D. programs.
