Molecular Characterization of the Mouse Superior Lateral Parabrachial Nucleus through Expression of the Transcription Factor Runx1

Chrissandra J Zagami,Stefano Stifani,M Fabiana Kubke

doi:10.1371/journal.pone.0013944

Chrissandra J Zagami, Stefano Stifani + Show 1 more

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https://doi.org/10.1371/journal.pone.0013944

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Abstract

BackgroundThe ability to precisely identify separate neuronal populations is essential to the understanding of the development and function of different brain structures. This necessity is particularly evident in regions such as the brainstem, where the anatomy is quite complex and little is known about the identity, origin, and function of a number of distinct nuclei due to the lack of specific cellular markers. In this regard, the gene encoding the transcription factor Runx1 has emerged as a specific marker of restricted neuronal populations in the murine central and peripheral nervous systems. The aim of this study was to precisely characterize the expression of Runx1 in the developing and postnatal mouse brainstem.Methods and Principal FindingsAnatomical and immunohistochemical studies were used to characterize mouse Runx1 expression in the brainstem. It is shown here that Runx1 is expressed in a restricted population of neurons located in the dorsolateral rostral hindbrain. These neurons define a structure that is ventromedial to the dorsal nucleus of the lateral lemniscus, dorsocaudal to the medial paralemniscal nucleus and rostral to the cerebellum. Runx1 expression in these cells is first observed at approximately gestational day 12.5, persists into the adult brain, and is lost in knockout mice lacking the transcription factor Atoh1, an important regulator of the development of neuronal lineages of the rhombic lip. Runx1-expressing neurons in the rostral hindbrain produce cholecystokinin and also co-express members of the Groucho/Transducin-like Enhancer of split protein family.ConclusionBased on the anatomical and molecular characteristics of the Runx1-expressing cells in the rostral hindbrain, we propose that Runx1 expression in this region of the mouse brain defines the superior lateral parabrachial nucleus.

Highlights

The brainstem is composed of a multitude of separate nuclei involved in the control and integration of key somatic and autonomic processes [1]
By E12.5 a previously uncharacterized group of ß-gal+ cells was visible in a dorsolateral position of the rostral hindbrain (Fig. 1B), near the border with the midbrain, suggesting that Runx1 expression becomes activated in this region between E11.5 and E12.5
Cells expressing ß-gal were detected in the dorsolateral rostral hindbrain throughout embryonic development (Fig. 1C and 1D) and expression persisted into adulthood (Fig. 2 and supporting information Fig. S1)

Summary

Introduction

The brainstem is composed of a multitude of separate nuclei involved in the control and integration of key somatic and autonomic processes [1]. The basic-helix-loop-helix transcription factor, Atoh (atonal homolog 1), has been shown to be essential for the generation of a number of brainstem neuronal populations derived from the rhombic lip (RL), which is the dorsal-most proliferative neuroepithelium of the developing hindbrain [3,4] Such regulators of cell fate can be used as specific molecular markers to further improve our understanding of the development of brainstem neurons. The ability to precisely identify separate neuronal populations is essential to the understanding of the development and function of different brain structures This necessity is evident in regions such as the brainstem, where the anatomy is quite complex and little is known about the identity, origin, and function of a number of distinct nuclei due to the lack of specific cellular markers. The aim of this study was to precisely characterize the expression of Runx in the developing and postnatal mouse brainstem

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