The online version of this article (doi:10.1007/s00429-014-0980-9) contains supplementary material, which is available to authorized users.
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.
Supplementary material 1 ESM1. Maximum intensity z projection through E13.5 Nkx6.2tmcre/+; tdTomatoflox/+; Gad67gfp/+ horizontal section. Image stacks were taken every 20 min. The video speed is 3 frames/second. The inset shows a magnification of the area of interest. The arrow points a migrating single neuron. Related still images are shown in Fig. 3f-h. (MP4 13,822 kb)
Gulcebi MI, Ketenci S, Linke R, Hacıoğlu H, Yanalı H, Veliskova J, Moshé SL, Onat F, Çavdar S (2012) Topographical connections of the substantia nigra pars reticulata to higher-order thalamic nuclei in the rat. Brain Res Bull 10(87):312–318 CrossRef
Lahti L, Achim K, Partanen J (2013) Molecular regulation of GABAergic neuron differentiation and diversity in the developing midbrain. Acta Physiol 207:616–627 CrossRef
Moreno-Bravo JA, Martínez-López JE, Puelles E (2012) Mesencephalic neuronal populations: new insights on the ventral differentiation programs. Histol Histopathol 27:1529–1538 PubMed
Oliver G, Mailhos A, Wehr R, Copeland N, Jenkins NA, Gruss P (1995) Six3, a murine homologue of the sine oculis gene, demarcates the most anterior border of the developing neural plate and is expressed during eye development. Development 121:4045–4055 PubMed
Puelles E, Martinez-de-la-Torre M, Watson C, Puelles L (2012) Midbrain, chap. 10. In: Watson C, Paxinos G, Puelles L (eds) The mouse nervous system. Academic Press, London, pp 337–359
Verney C, Zecevic N, Puelles L (2001) Structure of longitudinal brain zones that provide the origin for the substantia nigra and ventral tegmental area in human embryos, as revealed by cytoarchitecture and tyrosine hydroxylase, calretinin, calbindin, and GABA immunoreactions. J Comp Neurol 429(1):22–44 CrossRefPubMed
- Mesencephalic origin of the rostral Substantia nigra pars reticulata
M. Pilar Madrigal
Juan A. Moreno-Bravo
Jesús E. Martínez-López
- Springer Berlin Heidelberg
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