The serine protease homologue, Scarface, is sensitive to nutrient availability and modulates the development of the Drosophila blood brain barrier.

The adaptable transcriptional response to changes in food availability not only ensures animal survival, but also lets progressing with embryonic development. Interestingly, the central nervous system is preferentially protected to periods of malnutrition, a phenomenon known as 'brain sparing'. However, the mechanisms that mediates this response remains poorly understood. To get a better understanding of this, we used Drosophila melanogaster as a model, analysing the transcriptional response of neural stem cells (neuroblasts) and glia of the blood-brain barrier (BBB), from larvae of both sexes, during nutrient restriction using targeted DamID. We found differentially expressed genes in both neuroblasts and glia of the BBB, although the effect of nutrient deficiency was primarily observed in the BBB. We characterised the function of a nutritional sensitive gene expressed in the BBB, the serine protease homologue, scarface (scaf). Scaf is expressed in subperineurial glia in the BBB in response to nutrition. Tissue-specific knockdown of scaf increases subperineurial glia endoreplication and proliferation of perineurial glia in the blood-brain barrier. Furthermore, neuroblast proliferation is diminished upon scaf knockdown in subperineurial glia. Interestingly, re-expression of Scaf in subperineurial glia is able to enhance neuroblast proliferation and brain growth of animals in starvation. Finally, we show that loss of scaf in the blood-brain barrier increases the sensitivity to drugs in adulthood suggesting a physiological impairment. We propose that Scaf integrates the nutrient status to modulate the balance between neurogenesis and growth of the BBB, preserving the proper equilibrium between the size of the barrier and the brain.SIGNIFICANCE STATEMENT:The Drosophila Blood-brain barrier (BBB) separates the central nervous system from the open circulatory system. The BBB glia is not only acting as physical segregation of tissues but participates in the regulation of the metabolism and neurogenesis during development. Here we analyse the transcriptional response of the BBB glia to nutrient deprivation during larval development, a condition in which protective mechanisms are switched on in the brain. Our findings show that the gene scarface reduces growth in the BBB, while promoting the proliferation of neural stem, assuring the balanced growth of the larval brain. Thus, Scarface would link animal nutrition with brain development, coordinating neurogenesis with the growth of the BBB.