Abstract
Specification of the myriad of unique neuronal subtypes found in the nervous system depends upon spatiotemporal cues and terminal selector gene cascades, often acting in sequential combinatorial codes to determine final cell fate. However, a specific neuronal cell subtype can often be generated in different parts of the nervous system and at different stages, indicating that different spatiotemporal cues can converge on the same terminal selectors to thereby generate a similar cell fate. However, the regulatory mechanisms underlying such convergence are poorly understood. The Nplp1 neuropeptide neurons in the Drosophila ventral nerve cord can be subdivided into the thoracic-ventral Tv1 neurons and the dorsal-medial dAp neurons. The activation of Nplp1 in Tv1 and dAp neurons depends upon the same terminal selector cascade: col>ap/eya>dimm>Nplp1. However, Tv1 and dAp neurons are generated by different neural progenitors (neuroblasts) with different spatiotemporal appearance. Here, we find that the same terminal selector cascade is triggered by Kr/pdm>grn in dAp neurons, but by Antp/hth/exd/lbe/cas in Tv1 neurons. Hence, two different spatiotemporal combinations can funnel into a common downstream terminal selector cascade to determine a highly related cell fate.
Highlights
During nervous system development, vast numbers of different neuronal subtypes are generated, and understanding the process of cell fate specification remains a major challenge
Neuronal subtype cell fate is established in a stepwise manner, starting with spatial and temporal cues that confer distinct identities to neural progenitors and trigger expression of terminal selector genes in the early-born neurons
We find that two different combinations of spatiotemporal cues, in two different neural progenitors, funnel onto the same terminal selector gene, which in turn activates a shared regulatory cascade, resulting in the specification of a similar neuronal cell subtype identity
Summary
Vast numbers of different neuronal subtypes are generated, and understanding the process of cell fate specification remains a major challenge. Studies have shown that establishment of distinct neuronal identities requires complex cascades of regulatory information, starting from spatial and temporal selector genes [1] and feeding onward to terminal selector genes [2,3], often acting in combinatorial codes to dictate final and unique cell fate [4,5,6]. One intriguing regulatory challenge pertains to the generation of highly related neuronal subtypes in different regions of the central nervous system (CNS). The appearance of highly related neurons in different regions and at distinct developmental time-points clearly indicates that different spatial and temporal cues can converge to trigger the same terminal selector code, to thereby trigger a similar final cell fate.
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