Binary fate decisions in differentiating neurons

Abstract

Neural cell fate programs must generate an enormous number of neurons with distinct adult functions. The decision to choose one neuronal subtype from two alternatives--a binary fate decision--is one way to diversify neuronal subtypes during nervous system development. Recent progress has been made in describing the genetic programs that define late-stage neuronal identity. Here, we review mechanisms that control how such fate decisions generate two different postmitotic, terminally differentiated neuronal subtypes. We survey examples from Caenorhabditis elegans and Drosophila that demonstrate different modes of binary neuronal fate specification that depend on cell division, lineage, stochastic gene expression, or extracellular signals. Comparison of these strategies reveals that, although organisms use diverse approaches to generate neural diversity, some common themes do exist.

Figure 1. General Modes of Binary Cell Fate Decisions

Gray circles represent undifferentiated cells prior to fate choice; Blue and Red circles are differentiated cells that have acquired fate subtypes.

Figure 2. AIY and SMDD terminal differentiation is induced by an asymmetric cell division

a) Schematic of lateral view of C. elegans head showing positions of left adult AIY (Red) and SMDD (Purple) neurons with projections. b) Mechanism of asymmetric cell division for AIY and SMDD fate. Wnt signaling induces a higher SYS-1/POP-1 ratio in the posterior daughter cell (presumptive AIY), which causes POP-1, in conjunction with TTX-3, to activate expression of CEH-10 in posterior cell only. See text for details.

Figure 3. Bilaterally asymmetric ASEL/ASER post-mitotic differentiation induced by an early embryonic event

a) In 4-cell embryo, Delta/Notch signaling (apx-1 to glp-1) induces fate difference between ABa and ABp blastomeres. ASEL always descends from ABa blastomere lineage, while ASER always descends from ABp blastomere. Forked pathway indicates cell divisions along anterior/posterior axis. At a hybrid state, ASE-R/L both express specific subtype genes. A bistable feedback loop then mediates terminal differentiation of ASE-R or L fates. b) Schematic of C. elegans head showing position of adult ASEL (yellow) and ASER (Green) neurons with projections.

Figure 4. Photoreceptor neuron subtype specification for Drosophila Color Vision

a) A single ommatidium contains 8 photoreceptors. In the middle, R7 and R8 are involved in color vision. b) R7 subtypes are specified by stochastic expression of the transcription factor spineless (ss). c) R8 subtypes are specified by an instructive signal from R7. A bistable transcriptional feedback loop in R8 mediates the Rhodopsin output. ‘p’ is ‘pale’ subtype, ‘y’ is ‘yellow’ subtype. d) Fly retina showing a random mosaic of photoreceptor subtypes with antibody stains of R8 Rhodopsins: Rh6 (Red) in ‘y’ subtype, Rh5 (Blue) in ‘p’ subtype.