Abstract

Promoting the regeneration or survival of retinal ganglion cells (RGCs) is one focus of regenerative medicine. Homeobox Barhl transcription factors might be instrumental in these processes. In mammals, only barhl2 is expressed in the retina and is required for both subtype identity acquisition of amacrine cells and for the survival of RGCs downstream of Atoh7, a transcription factor necessary for RGC genesis. The underlying mechanisms of this dual role of Barhl2 in mammals have remained elusive. Whole genome duplication in the teleost lineage generated the barhl1a and barhl2 paralogues. In the Zebrafish retina, Barhl2 functions as a determinant of subsets of amacrine cells lineally related to RGCs independently of Atoh7. In contrast, barhl1a expression depends on Atoh7 but its expression dynamics and function have not been studied. Here we describe for the first time a Barhl1a reporter line in vivo showing that barhl1a turns on exclusively in subsets of RGCs and their post-mitotic precursors. We also show transient expression of barhl1a:GFP in diencephalic neurons extending their axonal projections as part of the post-optic commissure, at the time of optic chiasm formation. This work sets the ground for future studies on RGC subtype identity, axonal projections and genetic specification of Barhl1a-positive RGCs and commissural neurons.

Highlights

  • Promoting the regeneration or survival of retinal ganglion cells (RGCs) is one focus of regenerative medicine

  • Taking advantage of the zebrafish transgenesis combined with accessibility to 3D time-lapse imaging[21,22,23,24,25] we have previously shown that barhl2-expressing amacrine subtypes consistently arise within the lineage of Atoh[7] upon reproducible asymmetrical divisions of RGC progenitors[20]

  • Barhl1a in the retina is up-regulated in a subset of atoh7-expressing post-mitotic RGC precursors

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Summary

Introduction

Promoting the regeneration or survival of retinal ganglion cells (RGCs) is one focus of regenerative medicine. Barhl[2] is both sufficient and essential for determining the subtype specific identity of amacrine cells as well as to promote the maturation and survival of RGCs. Lastly, the expression of barhl[2] in RGCs appears to depend on Atoh[7] ( known as Ath5) – a bHLH transcription factor required for the specification of RGCs in vertebrates[13,14,15,16,17,18,19]. Retinal expression of barhl1a and barhl[2] is retained, but these two paralogs appear to have diversified their function in retinal lineages[10] In favour of this hypothesis, studies have shown that, to the mammalian counterpart, Barhl[2] is an amacrine cell www.nature.com/scientificreports subtype identity-biasing factor downstream of the transcription factor Ptf1a20. This study thereby provides the foundation for further investigations of the role of Barhl1a transcription factors in nerve cell subtype identity acquisition and maintenance in this in vivo model system

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