Timing brain development

Spatial and temporal cues acting in sequence may help developing neurons become specialized cell types.
Digest
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Image credit: Sonia Sen (CC BY 4.0)

The human brain is considered to be the most complicated object in the universe, but it only takes a handful of stem cells to make one. The process depends on two types of information: signals separated across space and time. Spatial cues tell a stem cell what type of cell it is going to be, while temporal cues work as molecular clocks to generate a sequence of different neurons over time. Together, these cues generate the large array of cell types in the nervous system.

Each stem cell occupies its own space in the developing body and receives its own spatial cues, but they all follow the same timeline. For example, proteins called transcription factors act as molecular clocks and interact with specific genes, telling the cell when to turn them on or off. The same series of transcription factors operates in different stem cells, but they have different effects. So far, it has been unclear whether spatial and temporal signals work independently or sequentially to generate new cell types.

To find out, Sen et al. studied two distinct, developing stem cells in fruit flies, which receive different spatial signals. Transcription factors only work if they are able to get to their target genes. Cells can open or close access to different genes by changing the structure of the chromatin wrapping that surrounds the genes. In the experiments, a marker was used to reveal the areas of open chromatin in each of the cells. Another marker was used to track the transcription factors. The results showed that the areas of open chromatin varied between stem cells. Moreover, although both cells used the same transcription factor called Hunchback, it targeted different genes in each stem cell. This was due to changes in the chromatin wrapping: Hunchback only acted in areas where the chromatin was open. This suggests that the spatial cues first sculpt the chromatin, making some genes easier to get to than others. Then, the same transcription factors go to the accessible gene, which will differ from one stem cell to another.

These findings help us to understand how different types of brain cells develop, which may also aid us in finding a way how to engineer specific cell types. If we could turn stem cells into different types of brain cells, it might help us to treat brain diseases. This may involve giving the right spatial signal before starting the temporal cues.