Patterns, Shapes, and Forms in Development
When a developmental biologist or developmental geneticist speaks about "patterning," They will usually describe the complex organization of organismal cell fates in space and time to form shapes, structures, organs, and body parts. They will then tell you about the mechanism by which initially equivalent cells in a developing tissue of an embryo assume complex forms and functions. They will also explain how during embryonic development patterning is often followed or accompanied by morphogenesis, the shaping of an organism through differentiation of cells, tissues, organs and organ systems. The differing cell states in the original "pattern" will then activate cell behaviours, such as proliferation, migration, adhesion, folding, which, in turn, will drive the development of all organismal shapes. Together, these fascinating embryological processes create all of the forms in the animal kingdom.
In 1859, Darwin wrote:
There is grandeur in this view of life.... and from so simple a beginning endless forms most beautiful and most wonderful have been, and are being, evolved.
Tissue patterning, morphogenesis, and growth are fundamental processes during the development of all multicellular organisms, through which endless forms have evolved. All of these processes are under tight genetic control, and it is genes and their intricate regulatory networks that ultimately govern the formation and location of all shapes and forms of the organism.
Our lab investigates the roles and activities of genes as the embryo develops. We are passionate about understanding how specific genes, mainly transcription factors whose encoded protein products bind DNA, control organismal patterning and morphogenesis. We are also committed to uncover how perturbations of transcriptional control during development can lead to birth defects that maim the embryo and the fetus.
Despite the wealth of knowledge on genes and regulatory networks that achieve lineage-specification, tissue patterning, and morphogenesis, questions remain about the mechanisms through which promiscuous transcription factors, which bind DNA indiscriminately, cooperate with select co-factors to instruct distinct developmental programs. We have devoted efforts to investigate the developmental roles of PBX homeodomain transcription factors of the TALE class, viewed primarily as co-factors for HOX proteins, the main architects of the body and appendage plans. A lingering question in developmental biology has centered on how PBX transcription factors, encoded by genes that are ubiquitously expressed in the vertebrate embryo, can confer functional specificity to HOX proteins, which display spatially-restricted localization in the embryo. We have used the vertebrate craniofacial complex, the limb bud, and the developing spleen to investigate the elusive mechanisms whereby PBX homedomain proteins themselves attain tissue-specific functions in the embryo during development.
We use the mouse embryo, our longstanding small-rodent friend, as a well-tractable model system. We combine classic developmental biology and embryology techniques, including transgenesis and genetic engineering in the mouse, with multi-omics approaches such as ChIP-seq, ATAC-seq, bulk RNA-seq, single-cell transcriptomics, and spatial transcriptomics on dissected embryonic tissues. More recently, we have also become fascinated by the exploration of how diverse anatomies and forms are generated from the same genes in different species. We are tackling these new investigations using additional model and "non-model" organisms, including chick, lizard, pig, chimp, and human embryos, in new projects of evolutionary developmental biology or evo-devo.
