U.S. Department of Health and Human Services

Genetics of Early Development

Andy Golden, Ph.D., Chief

About the Section

The Genetics of Early Development Section investigates the genetic requirements for the earliest stages of development using the model organism C. elegans. We are most interested in gamete differentiation, fertilization, and the signals to initiate embryonic development. To study these events, we have genetic mutants defective in each of these processes. We are also beginning to look at orthologs of disease genes that perturb early development.​

Oocytes in most organisms are fertilized prior to the completion of the meiotic divisions. Hence, the execution of these divisions is the first developmental event that the embryo must accomplish. The proper segregation of the oocyte chromosomes into polar bodies and the formation of a haploid maternal pronucleus are absolutely essential for normal development of all animals. Any errors in the first or second meiotic division will cause abnormal chromosome segregation, leading to aneuploidy and embryonic lethality, which are the causes of most spontaneous miscarriages in humans. These defects are also responsible for trisomy syndromes (e.g., Down syndrome).

Researchers in this section are interested in understanding the molecular mechanisms that are at work to regulate the meiotic divisions. We have been studying the maternal factors that control and regulate this process. Our new focus is on understanding the role that paternal factors may play in the oocyte meiotic divisions. The SPE-11 protein is the only factor known in C. elegans to be specifically donated to the embryo via the sperm. This work is discussed in greater detail in the Ongoing Projects description below.

The other main focus of the Genetics of Early Development Section is studying the C. elegans orthologs of genes, that when mutated, are known to cause disease in humans. This is a new project for us. We believe that by performing genetic suppressor screens with C. elegans mutants, we can learn more about the mechanism of action of a given gene. This knowledge should help further our understanding of the function of this gene in humans. We also believe that some of our suppressors could end up being potential therapeutic targets for human disease. This work is discussed in greater detail in the Ongoing Projects description below.

The long-term goal of our research is to identify factors that act within a specific developmental process in C. elegans and to determine whether the genes involved are conserved in human cells. Genes identified in nematodes could be more easily studied to understand the conserved functions these genes play in human cells.

Our basic understanding of how simple organisms grow and develop will aid in our understanding of more complex organisms like humans. Since thousands of nematode and human genes are conserved, we can more easily study these conserved genes in a rapidly developing simple organism like C. elegans. What we learn from this nematode may enlighten us as to the function of these genes in humans at the molecular and cellular levels.