Teije Middelkoop Group

Developmental mechanobiology

Institute of Molecular Genetics

Czech Academy of Sciences

 

Teije Middelkoop

The shape of an animal arises in a species-specific, step-wise fashion during embryonic development. During this sequence of events, collectively referred to as ‘embryo morphogenesis’, the embryo constantly remodels its shape. We are interested in the force-generating mechanisms that drive these shape changes.

The forces that drive embryo morphogenesis are generated by the cytoskeleton of embryonic cells and mainly arise in the actomyosin cortex: a dense two-dimensional network of cross-linked actin polymers residing directly underneath the plasma membrane. By pulling and twisting actin polymers, myosin motors and numerous accessory proteins, can generate active forces and torques within the cortical layer. Tight spatiotemporal regulation of these molecular-scale forces ultimately results in cellular-scale shape changes required for embryo morphogenesis. 

We use Caenorhabditis elegans and related nematode species to study how molecular forces generated within the actomyosin layer give rise to morphogenetic shape changes in early embryos. To this end, we combine the strength of C. elegans genetics with time-lapse imaging of early embryos (both at high-resolution and at super-resolution), quantitative image analysis and biophysical modelling.  

Actomyosin cortex of a one-cell Caenorhabditis elegans embryo
Figure: Actomyosin cortex of a one-cell Caenorhabditis elegans embryo. Actomyosin is visualized using fluorescent markers for filamentous actin (F-actin, magenta) and regions where active forces and torques are generated (Active RhoA, cyan). Bottom panels show a magnification of the region marked in the top panel.   

Future projects

In general, we aim to understand how molecular-scale forces drive the cellular scale rearrangements required for morphogenesis. More specifically, we previously showed that active torque generation in the actomyosin cortex is driven by an actin polymerase of the Formin family. These active torques lead to rotatory movements of embryonic cells and organismal left-right symmetry breaking. In the future, we aim at understanding how Formin-dependent active torques, generated at the molecular level, are converted to rotatory behaviour at the cellular and organismal level.

Contact

Institute of Molecular Genetics

Czech Academy of Sciences

Videnska 1083

14000 Prague 4

Czech Republic

CV

Since 2022

Group leader

Institute of Molecular Genetics, Czech Academy of Sciences

Prague, Czech Republic

2015-2022

Postdoc

Biotec, TU Dresden & Max Planck Institute of Molecular Cell Biology and Genetics

Dresden, Germany

2009-2014

PhD in developmental genetics

Hubrecht Institute

Utrecht, The Netherlands

Selected publications

Middelkoop TC, Garcia-Baucells J, Quintero-Cadena P, Pimpale L, Yazdi S, Sternberg P, Gross P, Grill SW. CYK-1/Formin activation in cortical RhoA signaling centers promotes organismal left-right symmetry breaking. PNAS, 118, 20, e2021814118, (2021) 

Pimpale LG, Middelkoop TC, Mietke A, Grill SW. Cell lineage-dependent chiral actomyosin flows drive cellular rearrangements in early Caenorhabditis elegans development. Elife 9, e54930, (2020)

Naganathan SR*, Middelkoop TC*, Fürthauer S*, Grill SW. Actomyosin-driven left-right asymmetry: from molecular torques to chiral self organization. Curr Opin Cell Biol 38, pp. 24-30, (2016)