Genetic Factors in Embryonic Development and Differentiation

Think about: keeping all your organs functional every day is already an enormous achievement by the proteins in your body, all of which are encoded on your genome. However, that’s by far not all of it: your genome also needs to orchestrate the very development and formation of all these organs systems and tissues of your body. We all once developped from a single fertilized egg cell. This cell divided to give rise to a chunk of stem cells, that all still look more or less the same. Then the magic starts happening: cells change shape, start moving relative to each other, divide and sometimes even die, all for the greater program. An inside and an outside, front and tail, back and belly, and left and right side develops – followed by the formation of highly complex organ systems. All of this is controlled through the sequential activation and deactivation of genetic factors encoded on your genome.

During the whole process, the full genomic sequence – these 3.2 billion letters that are so highly individual – is being passed on in every cell division and cell shape change. In the end cells in your eye’s retina and in your pancreatic beta-cells have still the same genome. However, they ended up using this genetic code in quite different ways. In the cells of your retina, genes encoding phototreceptors are highly actively transcribed whereas the gene that encodes the precursor for insulin is completely silenced.

The process during which these cells become so different to each other and start fullfilling very different functions, is called differentiation. Since differentiation is based on activation and silencing of genes, transcription factors are key regulators of differentiation. Transcription factors are proteins that bind DNA on specific locations, at certain time during development and/or upon specific triggers, i.e. signals that reach the cells from outside.

Differentiation fascinated Theresa from early on. So in her MSc thesis at Karolinska Institute in Stockholm she studied the transcription factor MAGI1 during the development of the rodent brain. Completely captivated by brain development, Theresa went on to do a PhD in the Driever Lab at Freiburg University. There she studied the homeobox transcription factor BSX in the embryonic development of the zebrafish forebrain. She employed genetic gain- and loss-of-function studies to characterize BSX expression and functions in the epithalamus (Schredelseker and Driever, 2018) and the hypothalamus (Schredelseker and Driever, 2020 and Schredelseker et al, 2020). You can find a more personal account on Theresa’s journey with the Bsx gene here. Readers interested in more details about Theresa’s dissertation work or genetic factors in embryonic brain development are referred to Theresa’s PhD thesis.

After completion of her PhD thesis, Theresa went on to study genetic factors in embryonic development – this time in a more clinical context. After she collaborated with Ekkehart Lausch’s group already during her PhD, she took on a short-term postdoctoral research position in the Lausch group at the University Hospital in Freiburg. There she studied the role of TRIP11 in skeletal malformations like Odontochondrodysplasia 1 or Achondrogenesis Type Ia.