Optogenetic protein manipulation during asymmetric divisions in vertebrate brain development

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During brain development in vertebrate embryos (including man) individual cells known as progenitors divide to generate two daughter cells. In early development the two daughters are essentially both copies of the original progenitor cell, i.e. they are both also progenitors that can themselves go on to divide and make two more cells. These cell divsions are called symmetric cell divisions because their two daughters have similar identities. A little later in development many progenitors will change the way they divide so that their two daughters are generated with different fates. For example one daughter will become another progenitor and be capable of dividing again, while the other daughter becomes a more specialised cell such as a neuron which is incapable of dividing. This type of cell division is called an asymmetric cell division and is of fundamental importance to brain development because it allows the brain to get bigger by repeatedly generating more cells (the daughter that is the progenitor does this) while also making some cells that construct the neural circuits that underlie animal behaviour (the daughter that is the neuron does this by connecting and communicating to other neurons). This proposal aims to understand the biological mechanisms that determine whether a cell division is symmetric or asymmetric. Specifically it will test a long held hypothesis that asymmetric divisions are determined by the asymmetric inheritance of specific proteins from the progenitor cell to the two daughters, for example one daughter inherits certain proteins that push it towards becoming a neuron, while the other daughter does not inherit the same proteins and therefore has a different identity. To achieve asymmetric inheritance of a protein the progenitor cell needs to have a mechanism that moves the protein into only one of its daughters as it splits into two. We have developed a new method that allows us to use light of particular wavelength to manipulate protein localisation in individual progenitor cells in a living embryo. This allows us to experimentally control protein localisation during cell divisions and thus control whether proteins are symmetrically or asymmetrically inherited. This will allow us to determine whether asymmetric protein inheritance can explain the occurrence of asymmetric divisions in a vertebrate embryo.