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.

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In eukaryotic cells, gene expression is highly regulated at many layers. Nascent RNA molecules are assembled into ribonucleoprotein complexes that are then released into the nucleoplasmic milieu and transferred to the nuclear pore complex for nuclear export. RNAs are then either translated or transported to the cellular periphery. Emerging evidence indicates that RNA-binding proteins play an essential role throughout RNA biogenesis, from the gene to polyribosomes. However, the sorting mechanisms that regulate whether an RNA molecule is immediately translated or sent to specialized locations for translation are unclear. This question is highly relevant during development and differentiation when cells acquire a specific identity. Here, we focus on the RNA-binding properties of heterogeneous nuclear ribonucleoproteins (hnRNPs) and how these mechanisms are believed to play an essential role in RNA trafficking in polarized cells. Further, by focusing on the specific hnRNP protein CBF-A/hnRNPab and its naturally occurring isoforms, we propose a model on how hnRNP proteins are capable of regulating gene expression both spatially and temporally throughout the RNA biogenesis pathway, impacting both healthy and diseased cells.

Combining genome-wide analyses of binding sites and expression profiles generates a model for the functional evolution of two SOXB paralogous proteins in neurogenesis.