Summary In the Drosophila optic lobes, 800 retinotopically organized columns in the medulla act as functional units for processing visual information. The medulla contains over 80 types of neurons, which belong to two classes: uni-columnar neurons have a stoichiometry of one per column, while multi-columnar neurons contact multiple columns. We show that combinatorial inputs from temporal and spatial axes generate this neuronal diversity: All neuroblasts switch fates over time to produce different neurons. The neuroepithelium that generates neuroblasts is also sub-divided into six compartments by the expression of specific factors. Uni-columnar neurons are produced in all spatial compartments independently of spatial input; they innervate the neuropil where they are generated. Multi-columnar neurons are generated in smaller numbers in restricted compartments and later move to their final position. The integration of spatial inputs by a fixed temporal neuroblast cascade thus acts as a powerful mechanism for generating neural diversity, regulating stoichiometry and the formation of retinotopy.

Understanding how complex brain wiring is produced during development is a daunting challenge. In Drosophila, information from 800 retinal ommatidia is processed in distinct brain neuropiles, each subdivided into 800 matching retinotopic columns. The lobula plate comprises four T4 and four T5 neuronal subtypes. T4 neurons respond to bright edge motion, whereas T5 neurons respond to dark edge motion. Each is tuned to motion in one of the four cardinal directions, effectively establishing eight concurrent retinotopic maps to support wide-field motion. We discovered a mode of neurogenesis where two sequential Notch-dependent divisions of either a horizontal or a vertical progenitor produce matching sets of two T4 and two T5 neurons retinotopically coincident with pairwise opposite direction selectivity. We show that retinotopy is an emergent characteristic of this neurogenic program and derives directly from neuronal birth order. Our work illustrates how simple developmental rules can implement complex neural organization.

Background: Reduced cerebral blood flow in parieto-occipital regions has been reported in neurodegenerative disorders using ASL. We aimed to investigate neuropsychiatric and neurodegenerative comorbidities that may associate with parieto-occipital region hypoperfusion. Methods: This was a retrospective single-center study. Between March 2017 to May 2018, adult patients who underwent brain MRI with the inclusion of ASL perfusion and who had bilateral reductions of CBF in the parieto-occipital regions were included. ASL was performed using a pseudo-continuous arterial spin labeling (pCASL) technique on 1.5T MR system. Age and gender-matched patients with no perfusion defect were concurrently collected. Comorbidity data was collected from EMR, including major depressive disorder, Alzheimer’s disease, Parkinson’s disease, Schizophrenia, anxiety disorder, hypertension, diabetes mellitus type II, coronary artery disease, and chronic kidney disease. A Pearson’s Chi-Square test was performed to assess for comorbidities associated with hypoperfusion of the parieto-occipital lobes. Results: Our patient cohort consisted of 93 patients with bilateral hypoperfusion in the parieto-occipital lobes and 93 age and gender-matched patients without corresponding perfusion defects based on ASL-CBF. Among the comorbidities assessed, there was a statistically significant association between hypoperfusion of the parieto-occipital lobes and major depressive disorder (p=0.004) and Parkinson’s disease (p=0.044). There was no statistically significant association for Alzheimer’s disease, generalized anxiety disorder, diabetes mellitus type II, hypertension, coronary artery disease, or chronic kidney disease. Conclusion: Major depressive disorder may be linked to regional parieto-occipital hypoperfusion on ASL.