Combinatorial Rules of Precursor Specification Underlying Olfactory Neuron Diversity

Abstract

Summary Background Sensory neuron diversity ensures optimal detection of the external world and is a hallmark of sensory systems. An extreme example is the olfactory system, as individual olfactory receptor neurons (ORNs) adopt unique sensory identities by typically expressing a single receptor gene from a large genomic repertoire. In Drosophila, about 50 different ORN classes are generated from a field of precursor cells, giving rise to spatially restricted and distinct clusters of ORNs on the olfactory appendages. Developmental strategies spawning ORN diversity from an initially homogeneous population of precursors are largely unknown. Results Here we unravel the nested and binary logic of the combinatorial code that patterns the decision landscape of precursor states underlying ORN diversity in the Drosophila olfactory system. The transcription factor Rotund (Rn) is a critical component of this code that is expressed in a subset of ORN precursors. Addition of Rn to preexisting transcription factors that assign zonal identities to precursors on the antenna subdivides each zone and almost exponentially increases ORN diversity by branching off novel precursor fates from default ones within each zone. In rn mutants, rn-positive ORN classes are converted to rn-negative ones in a zone-specific manner. Conclusions We provide a model describing how nested and binary changes in combinations of transcription factors could coordinate and pattern a large number of distinct precursor identities within a population to modulate the level of ORN diversity during development and evolution.

Drosophila Chemoreceptors: A Molecular Interface Between the Chemical World and the Brain

“…How do individual ORNs select the Ors that they express, from a family of 60 genes? A combinatorial code of transcription factors, including the POU domain transcription factor Acj6 and the Kruppel-like transcription factor Rotund, underlies much of the process [45, 46]; epigenetic mechanisms also contribute to receptor regulation in ORNs [47]. A code of regulatory elements upstream of Or genes acts in specifying their expression patterns [48].…”

Dendritic diversification through transcription factor-mediated suppression of alternative morphologies

“…Repression of alternative identities and morphologies by transcriptional regulators is an important driver of neuronal diversification during the development of sensory and motor systems (Jung et al, 2010;Li et al, 2013;Philippidou and Dasen, 2013;Gordon and Hobert, 2015). Transcription factors may suppress alternative programs of differentiation and promote neuronal diversity by direct repression of other transcription factors, repression of their downstream target genes, or by competitive binding of common cofactors to block transcription factor function Borromeo et al, 2014;Gordon and Hobert, 2015).…”

Mechanisms of Development and Evolution of the Insect Olfactory System

“…This sensilla contains three ORNs expressing Or47b, Or88a and Or65a, and project to non-overlapping glomeruli. B) Decision tree of precursor cells as modified from Li et al (46). Precursors make hierarchical decisions regarding which sensilla type and subtype they will form.…”

“…given precursor cell will give rise to are determined by proneural basic helix-loop-helix transcription factors, Amos, Lozenge, and Atonal [38][39][40], which are required for the development of basiconic/trichoid and coeloconic sensilla SOPs, respectively. Sensilla subtype identity decisions of SOPs on the other hand are dictated by the combinations of transcription factors such as Rotund, Engrailed and Daschund and ultimately restrict the particular ORN classes that can be formed from a given precursor cell ( Figure 1B) [36,41,46]. Once the SOPs have restricted their differentiation potentials, another set of transcription factors including acj6, pdm3 and onecut as well as cell-cell interactions mediated....decisions [37,[42][43][44].…”

“…Recent research has provided further insight into the transcription factory-mediated precursor cell decisions responsible for the diversity of olfactory neurons [46]. Under this model, sensory precursor cells undergo nested, bifurcating cell fate decisions, with the concurrent use of the same transcription factors in parallel lineages to give rise to the different sets of ORNs that underlie each sensilla subtype.…”