Colorado State University

The genome is the blueprint of the body... ...but it is unclear how genetic information is accessed to produce the shape and form of the body. Biologists have long sought to determine how transcriptomes – the sets of mRNA transcripts – change during embryogenesis in an attempt to gain insight into this question.

Why is this hard to study? With the advent of high throughput genome sequencing, it should be possible to map how transcriptomes change through embryogenesis. However, it is difficult to obtain enough material from specific cell types for use in genomic assays. Further, it is often difficult, in most animals, to link a transcriptome profile from cells in an early stage of development to their eventual fates in a later stage.

How does our lab meet these challenges? Using hand dissection coupled with low-input RNA-seq, we have generated cell-specific transcriptome profiles in early embryonic stages of the nematode worm, C. elegans. To link these genome-wide assays to specific developmental fates, we rely on the determinant property of C. elegans development. C. elegans embryos produce an invariant number of cells that divide with highly reproducible timing and certain fate allowing us to link embryonic cells in early stages to their eventual fates.

A complementary approach: In addition to using high-resolution genomic assays, we also use high-resolution microscopy (smFISH) to observe individual molecules of mRNA transcripts with sub-cellular resolution in nematode embryos. This technique allows us to test for factors (sequences and proteins) required for mRNA regulation.

Projects: We are currently focused on the following research objectives:

• Identifying mechanisms responsible for mRNA patterning prior to the onset of zygotic transcription and in its earliest stages
• Assessing the functional significance of cell-specific mRNAs
• Identifying general features of lineage-specific transcriptional activation