Research group Group Erickson

Formation of the craniofacial skeleton during embryonic development is central for basic life activities like breathing, eating, verbal communication, and personal identity. This process is driven by a highly complex genetic network that involves numerous cellular interactions, and is sensitive to physical, mechanical, chemical, and nutritional inputs from the environment. Heritable birth defects affecting the craniofacial skeleton are relatively common among newborns and are difficult to diagnose and treat. 

Since the discovery of the neural crest cell, which represents the cellular building block of the face, the basic understanding of the cell processes underlying facial formation has substantially improved. Cranial neural crest cells migrate from the dorsal neural tube into the presumptive facial prominences, and give rise to an ‘intermediate’ cell – the ectomesenchymal cell – which can then differentiate into numerous cell types including cartilage, bone, and other connective tissues. The molecular rules governing the functional heterogeneity of mesenchyme are unclear, and this represents a major aim of this research group. 

The advent of in vivo gene editing has helped biologists identify hundreds of genes that are essential for proper development of facial structures across various vertebrate species, and modern expression analysis techniques have helped us identify their spatiotemporal distributions in the craniofacial compartments. Some of these key genes appear to bestow positional information to craniofacial cells. How positional identity influences cell behavior during tissue formation remains mysterious, and is a second major question we aim to answer.

Genome-wide association studies (GWAS) have also contributed significantly to our understanding of the genetic architecture underlying disease and normal variation of the human face. Many of the variants that are highly significantly associated with facial traits or pathologies are not found inside genes, but in intergenic regions, introns, and long non-coding RNAs. In our lab we attempt to determine the functional roles of noncoding cis-regulatory elements. The highly combinatorial nature of enhancer-gene interactions is an endlessly fascinating puzzle, with important implications for interpreting variants of uncertain significance in clinical genetics. 

To answer these questions, we use gene editing for lineage tracing, molecular activity reports, and genetic perturbations for testing gain and loss-of-function, in combination with epigenomic and transcriptomic assays to profile cell states, spatial analysis for morphometric outcomes (ST, light sheet, confocal, micro-CT), computational genomics and single-cell analysis.