A shared transcriptional code orchestrates temporal patterning of the central nervous system.

Andreas Sagner,Thomas Watson,Isabel Zhang,Jorge Lazaro,James Briscoe,Manuela Melchionda,Claude Desplan

doi:10.1371/journal.pbio.3001450

Andreas Sagner, Thomas Watson + Show 5 more

Open Access

https://doi.org/10.1371/journal.pbio.3001450

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Abstract

The molecular mechanisms that produce the full array of neuronal subtypes in the vertebrate nervous system are incompletely understood. Here, we provide evidence of a global temporal patterning program comprising sets of transcription factors that stratifies neurons based on the developmental time at which they are generated. This transcriptional code acts throughout the central nervous system, in parallel to spatial patterning, thereby increasing the diversity of neurons generated along the neuraxis. We further demonstrate that this temporal program operates in stem cell-derived neurons and is under the control of the TGFβ signaling pathway. Targeted perturbation of components of the temporal program, Nfia and Nfib, reveals their functional requirement for the generation of late-born neuronal subtypes. Together, our results provide evidence for the existence of a previously unappreciated global temporal transcriptional program of neuronal subtype identity and suggest that the integration of spatial and temporal patterning mechanisms diversifies and organizes neuronal subtypes in the vertebrate nervous system.

Highlights

In mammals, the function of the nervous system depends on hundreds of molecularly and functionally distinct cell types [1]
We previously identified sets of transcription factor (TF) that are expressed in multiple subsets of neurons in the spinal cord
As the onset of expression of these TFs occurred at different times during development, we speculated that they subdivide neurons in the spinal cord based on their time point of birth [33] (Fig 1A)

Summary

Introduction

The function of the nervous system depends on hundreds of molecularly and functionally distinct cell types [1]. This diversity requires the generation of different neuronal subtypes at the right place, time, and quantity during development. This guides the wiring of functioning neural circuits. Even within the same region of the nervous system, most neuronal classes can be further partitioned into distinct subtypes based on molecular and functional properties [4,5,6,7,8,9]

Results

Discussion

Experimental procedures Animal welfare