Zic1 levels regulate mossy fiber neuron position and axon laterality choice in the ventral brain stem.

Abstract:

:Pontine gray neurons of the brain stem are a major source of mossy fiber (MF) afferents to granule cells of the cerebellum. Achieving this connectivity involves an early regionalization of pontine gray neuron cell bodies within the brainstem pontine nuclei, as well as establishing the proper ratio of crossed versus uncrossed MF projections to contralateral versus ipsilateral cerebellar territories. Here, we report expression of the transcription factor Zic1 in newly postmitotic pontine gray neurons and present functional experiments in embryonic and postnatal mice that implicate Zic1 levels as a key determinant of pontine neuron cell body position within the pons and axon laterality. Reducing Zic1 levels embryonically via in utero electroporation of short hairpin RNA interference (shRNAi) vectors shifted the postnatal distribution of pontine neurons from caudolateral to rostromedial territories; by contrast, increasing Zic1 levels resulted in the reciprocal shift, with electroporated cells redistributing caudolaterally. Associated with the latter was a change in axon laterality, with a greater proportion of marked projections now targeting the ipsilateral instead of contralateral cerebellum. Zic1 levels in pontine gray neurons, therefore, play an important role in the development of pontocerebellar circuitry.

journal_name

Neuroscience

journal_title

Neuroscience

authors

Dipietrantonio HJ,Dymecki SM

doi

10.1016/j.neuroscience.2009.02.082

subject

Has Abstract

pub_date

2009-09-01 00:00:00

pages

560-73

issue

3

eissn

0306-4522

issn

1873-7544

pii

S0306-4522(09)00333-9

journal_volume

162

pub_type

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