Abstract
The extensive genetic regulatory flows underlying specification of different neuronal subtypes are not well understood at the molecular level. The Nplp1 neuropeptide neurons in the developing Drosophila nerve cord belong to two sub-classes; Tv1 and dAp neurons, generated by two distinct progenitors. Nplp1 neurons are specified by spatial cues; the Hox homeotic network and GATA factor grn, and temporal cues; the hb -> Kr -> Pdm -> cas -> grh temporal cascade. These spatio-temporal cues combine into two distinct codes; one for Tv1 and one for dAp neurons that activate a common terminal selector feedforward cascade of col -> ap/eya -> dimm -> Nplp1. Here, we molecularly decode the specification of Nplp1 neurons, and find that the cis-regulatory organization of col functions as an integratory node for the different spatio-temporal combinatorial codes. These findings may provide a logical framework for addressing spatio-temporal control of neuronal sub-type specification in other systems.
Highlights
The nervous system contains a myriad of different neuronal sub-types, and understanding cell fate specification remains a major challenge
We focus on two related neuropeptide neurons in the Drosophila central nervous system, for which an extensive genetic pathway has been identified
Our findings reveal that different spatial and temporal cues converge on different enhancers of a key initiator terminal selector gene, which triggers a feedforward cascade of sequential enhancer activation, landing on the enhancer of the neuropeptide gene
Summary
The nervous system contains a myriad of different neuronal sub-types, and understanding cell fate specification remains a major challenge. With respect to spatial information, the Hox homeotic selector genes, expressed in distinct but partly overlapping domains along the antero-posterior axis of the central nervous system, have been extensively studied for their role in cell fate specification [reviewed in [7, 8]]. Studies have revealed that the Hox spatial information can converge with temporal cues to thereby specify neuronal subtypes [11] While these functional genetic studies have provided insight into the genetic mechanisms underlying neuronal subtype specification, it is largely unclear how the broader spatio-temporal cues are molecularly integrated to cause discrete terminal selector gene expression, and how terminal selectors feed forward to final cell identity
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