Alladi Ramakrishnan Hall

Generating neural diversity by integrating spatial and temporal cues within neural stem cells

Sonia Sen

Tata Institute of Genomics and Science, inStem centre, Bengaluru

Developmental studies in both vertebrates and invertebrates have contributed to our current knowledge of how neuronal diversity is generated in the brain. A few common principles have emerged from these studies. Neural stem cells (NSC) use two axes of information, spatial and temporal, to diversity. NSCs experience unique spatial cues based on their position along the anterio-posterior (AP) and dorso-ventral (DV) axes of the developing embryo. This diversifies an initially homogenous pool of stem cells. Then temporal cues, consisting of sequential changes in gene expression within the NSC allows them to generate different neurons over time. The integration of diverse spatial cues with the same temporal series within NSCs is thought to generate the entire complement of neural cell types during development.

This is best studied in the Drosophila NSCs, where the temporal series Hb>Kr>Pdm>Cas, specifies different neural identities in spatially distinct NSCs. How do the same temporal transcription factors (tTFs) specify different identities in different NSCs? I will present data that shows that spatially distinct NSCs have distinct chromatin landscapes and this allows the first tTF, Hb, to occupy different loci in them. We propose that spatial transcription factors (sTFs) establish distinct chromatin landscapes in neural stem cells. In support of this, we show that the occupancy of the sTF, gsb, corresponds to open chromatin in a NSC- specific way. Finally, I will discuss ideas about how sTFs might establish and maintain NSC lineage identities throughout development.