Mesencephalic origin of the rostral Substantia nigra pars reticulata.

M Pilar Madrigal,Eduardo Puelles,Jesús E Martínez-López,Salvador Martínez,Juan A Moreno-Bravo

doi:10.1007/s00429-014-0980-9

Abstract

In embryonic development, the neurons that will constitute a heterogeneous nucleus may have distinct origins. The different components of these populations reach their final location by radial and tangential migrations. The Substantia nigra pars reticulata (SNR) presents a high level of neuronal heterogeneity. It is composed by GABAergic neurons located in the mes-diencephalic basal plate. These inhibitory neurons usually display tangential migrations and it has been already described that the caudal SNR is colonized tangentially from rhombomere 1. Our aim is to unveil the origin of the rostral SNR. We have localized a Nkx6.2 positive ventricular domain located in the alar midbrain. Nkx6.2 derivatives’ fate map analysis showed mainly a rostral colonization of this GABAergic neuronal population. We confirmed the mesencephalic origin by the expression of Six3. Both transcription factors are sequentially expressed along the differentiation of these neurons. We demonstrated the origin of the rostral SNR; our data allowed us to postulate that this nucleus is composed by two neuronal populations distributed in opposite gradients with different origins, one from rhombomere 1, caudal to rostral, and the other from the midbrain, rostral to caudal. We can conclude that the SNR has multiple origins and follows complex mechanisms of specification and migration. Our results support vital information for the study of genetic modifications in these extremely complex processes that result in devastating behavioral alterations and predisposition to psychiatric diseases. Understanding the development, molecular identity and functional characteristics of these diverse neuronal populations might lead to better diagnosis and treatment of several forms of neurological and psychiatric disease.Electronic supplementary materialThe online version of this article (doi:10.1007/s00429-014-0980-9) contains supplementary material, which is available to authorized users.

Highlights

The Substantia nigra (SN) is a complex nucleus located in the mesencephalic basomedial territory (Puelles 2007; Moreno-Bravo et al 2012; Puelles et al 2012) but it is extended along the pretectum, thalamus and prethalamus
In E18.5 embryos induced by tamoxifen at E8.5, we detected a small number of Nkx6.2 GABAergic neurons (GABAn) in the Substantia nigra pars reticulata (SNR) (Fig. 1a)
We used immunohistochemistry for tyrosine hydroxylase to detect the dopaminergic neurons of the SN pars compacta (SNC) and confirm the location of the green fluorescent protein (GFP) positive GABAn in the SNR (Fig. 1e)

Summary

Introduction

The Substantia nigra (SN) is a complex nucleus located in the mesencephalic basomedial territory (Puelles 2007; Moreno-Bravo et al 2012; Puelles et al 2012) but it is extended along the pretectum, thalamus and prethalamus (diencephalic prosomeres) It is divided into a pial superficial part, SN pars reticulata (SNR), constituted by GABAergic neurons (GABAn) and a more internal SN pars compacta (SNC), primarily containing dopaminergic neurons (Hanaway et al 1970). The SNR and the internal segment of the globus pallidus provide the major output projections of the basal ganglia system where the final stage of information processing takes place These cell groups are mainly composed of GABAn; they integrate inputs from all other components of the basal ganglia system (striatum, globus pallidus, subthalamic nucleus) and elaborate the message sent by this system to extrinsic structures (Rinvik et al 1976). The SNR constitutes one of the main output pathways of the basal ganglia system regulating mainly voluntary movements (Beckstead et al 1979)

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