Pax7 is requisite for maintenance of a subpopulation of superior collicular neurons and shows a diverging expression pattern to Pax3 during superior collicular development

Jennifer A Thompson,Mel Ziman,Ahmed Mansouri,Andreas Zembrzycki

doi:10.1186/1471-213x-8-62

Abstract

BackgroundPax7 encodes a transcription factor well-established as an important determinant of mesencephalic identity and superior collicular development. Pax7 mutant mice, however, present with no obvious morphological impairments to the superior colliculus. This finding is paradoxical and has been attributed to functional redundancy afforded by its paralogue Pax3. Here we utilise Pax7 mutant mice to investigate the precise role of this important developmental regulator during superior collicular development and neuronal specification/differentiation. We also assess its spatiotemporal relationship with Pax3 during embryonic development.ResultsAnalysis of the superior colliculus of Pax7 mutant and wildtype mice at a variety of developmental timepoints revealed that whilst correct initial specification is maintained, a subpopulation of dorsal mesencephalic neurons is lost at early postnatal stages. Moreover, a comparative analysis of embryonic Pax3 and Pax7 expression profiles indicate that Pax3 expression overlaps extensively with that of Pax7 initially, but their expression domains increasingly diverge as development progresses, coinciding spatiotemporally with neuronal differentiation and maturation of the tissue. Furthermore, Pax3 expression is perturbed within the CNS of embryonic Pax7 mutant mice.ConclusionIn summary, these results demonstrate that during superior collicular development, Pax7 is required to maintain a subpopulation of dorsal, mesencephalic neurons and partially regulates, spatiotemporally, Pax3 expression within the CNS. The differential nature of Pax7 and Pax3 with respect to neuronal differentiation may have implications for future stem cell therapies aimed at exploiting their developmental capabilities.

Highlights

Pax7 encodes a transcription factor well-established as an important determinant of mesencephalic identity and superior collicular development
We have analysed Pax7 mutant mice [10] relative to wildtype at key stages of development and results indicate that a subpopulation of neurons is lost during early postnatal stages. We show that this apparent loss of neurons is not due to aberrant specification or proliferation, or cell-fate switching/transdifferentiation to the astrocytic lineage, but rather appears due to the inability of Pax7 mutant mice to maintain a subpopulation of dorsal superior collicular neurons
Pax7+ cells recede from the mesencephalic ventricular zone, remnants of expression can still be detected at the dorsal ventricular surface, with cells noted at the ventral ventricular surface at certain mediolateral positions

Summary

Introduction

Pax encodes a transcription factor well-established as an important determinant of mesencephalic identity and superior collicular development. Present with no obvious morphological impairments to the superior colliculus. We utilise Pax mutant mice to investigate the precise role of this important developmental regulator during superior collicular development and neuronal specification/differentiation. It is evident that Pax is a multiplex contributor to correct CNS development This is exemplified by dynamic spatiotemporal expression patterns, occurring from early development and persisting in restricted regions throughout adulthood. Pax expression initially occurs in the neural tube and mesencephalon from very early stages [1,2] and is required for polarisation of the dorsoventral axis of the neural tube [3] and specification of the superior colliculus/tectum from the mesencephalic alar plate [4,5,6,7]. In the developing superior colliculus, graded expression of Pax establishes rostrocaudal and dorsoventral polarity. Expression of Pax localises within superior collicular neurons as development proceeds. Continued, graded expression into adulthood is thought to maintain a small population of dorsal neurons in the mature colliculus [7,9], the functional requirement for this feature remains obscure

Methods

Results

Discussion

Conclusion