822V Poster - 13. Neural development and physiology
Wednesday April 06, 4:00 PM - 7:00 PM

Differentiation signals from glia are fine-tuned to set neuronal numbers during development


Authors:
Anadika Prasad; Matthew Bostock; Ines Lago-Baldaia; Zaynab Housseini; Vilaiwan Fernandes

Affiliation: University College London

Keywords:
d. neuronal specification; k. glia

The number of neurons formed during development need to be tightly regulated to form functional neural circuits. Known strategies include regulating the number of neurons that are formed or that survive during development. Here, we study how neuronal numbers are regulated in the lamina neuropil of the visual system. The lamina is comprised of ~800 units or columns. Each column consists of six precursors, of which only five differentiate into the five lamina neuron types (L1-L5). The extra precursor is eliminated by apoptosis. This process is highly stereotyped with neuronal differentiation and apoptosis occurring invariantly in the same cell positions in each column. We asked how exactly five lamina neurons (and neuron types) differentiate from a pool of six precursors. Previously we showed that L1-L4 neurons are induced to differentiate by wrapping glia. Therefore, we focused on the extra precursor and the differentiating L5s. We uncovered that differential Hedgehog signaling levels along the length of columns pattern lamina precursors, such that the 2 precursors experiencing the lowest levels of signaling are specified as L5s. Thus, twice as many precursors are specified as L5s than undergo differentiation normally. We showed that in response to photoreceptor-derived Spitz, a glial population, the outer chiasm giant glia (xgO), secrete multiple ligands (Spitz and Collagen IV alpha 1) to induce L5 differentiation. Moreover, we found that the newly-induced L5 neurons antagonize differentiation signals from reaching the extra precursors, which as a result undergo apoptosis. Therefore, our results indicate that newly induced neurons limit the availability of glial differentiation signals which sets the number of L5 neurons in each lamina column. Furthermore, our work highlights how stereotyped patterns of programmed cell death in the lamina arise from extrinsic signals which reliably pattern the development of the nervous system.