The Long Journey of Pontine Nuclei Neurons: From Rhombic Lip to Cortico-Ponto-Cerebellar Circuitry.

Claudius F Kratochwil,Filippo M Rijli,Upasana Maheshwari

doi:10.3389/fncir.2017.00033

Claudius F Kratochwil, Filippo M Rijli + Show 1 more

Open Access

https://doi.org/10.3389/fncir.2017.00033

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Abstract

The pontine nuclei (PN) are the largest of the precerebellar nuclei, neuronal assemblies in the hindbrain providing principal input to the cerebellum. The PN are predominantly innervated by the cerebral cortex and project as mossy fibers to the cerebellar hemispheres. Here, we comprehensively review the development of the PN from specification to migration, nucleogenesis and circuit formation. PN neurons originate at the posterior rhombic lip and migrate tangentially crossing several rhombomere derived territories to reach their final position in ventral part of the pons. The developing PN provide a classical example of tangential neuronal migration and a study system for understanding its molecular underpinnings. We anticipate that understanding the mechanisms of PN migration and assembly will also permit a deeper understanding of the molecular and cellular basis of cortico-cerebellar circuit formation and function.

Highlights

The basal pontine nuclei (BPN) ( known as basilar pons, pontine gray nuclei or pontine nuclei (PN)) and the reticulotegmental nuclei (RTN) are located within the ventral portion of the pons
All mossy fiber precerebellar neurons, i.e., those contributing to external cuneate nucleus (ECN), lateral reticular nucleus (LRN), RTN and BPN, are derived from a defined dorsal domain of the rhombic lip specified by high Wnt1 expression levels and the expression of the basic helix-loop-helix transcription factor Atoh1 (Math1; Rodriguez and Dymecki, 2000; Machold and Fishell, 2005; Wang et al, 2005)
The PN can be considered as part of one of the most complex neuronal circuits within the brain— in terms of connectivity pattern and function

Summary

INTRODUCTION

The basal pontine nuclei (BPN) ( known as basilar pons, pontine gray nuclei or pontine nuclei (PN)) and the reticulotegmental nuclei (RTN) ( known as nucleus reticularis tegmenti pontis) are located within the ventral portion of the pons. All mossy fiber precerebellar neurons, i.e., those contributing to ECN, LRN, RTN and BPN, are derived from a defined dorsal domain of the rhombic lip specified by high Wnt expression levels and the expression of the basic helix-loop-helix (bHLH) transcription factor Atoh (Math; Rodriguez and Dymecki, 2000; Machold and Fishell, 2005; Wang et al, 2005). Precerebellar nuclei neurons are generated from distinct intersections of dorso-ventral (DV; Atoh1+/Wnt1+) and anterior-posterior (AP; Hox2–5+) progenitor pools, as assessed in several fate mapping studies using rhombomere- and DV progenitor-specific Cre and FLP recombinase expressing mouse lines, respectively (Rodriguez and Dymecki, 2000; Wingate, 2005; Fu et al, 2011; Di Meglio et al, 2013). The Ptf1a+ ION neurons are the first ones to be generated and to migrate (E10.5–E11.5), followed by the Atoh1+ LRN (E11.5–12.5), ECN (E11.5–12.5), RTN (E12.5–E13.5) and lastly the BPN (E13.5–E16.5) (Pierce, 1966; Altman and Bayer, 1987d; Machold and Fishell, 2005; Wang et al, 2005; Okada et al, 2007)

A LONG WAY TO GO

Findings

CONCLUSIONS AND OUTSTANDING QUESTIONS