Conserved and divergent functions of Pax6 underlie species-specific neurogenic patterns in the developing amniote brain.

Wataru Yamashita,Hitoshi Gotoh,Noriko Osumi,Takako Kikkawa,Masanori Takahashi,Tadashi Nomura,Katsuhiko Ono

doi:10.1242/dev.159764

Abstract

ABSTRACTThe evolution of unique organ structures is associated with changes in conserved developmental programs. However, characterizing the functional conservation and variation of homologous transcription factors (TFs) that dictate species-specific cellular dynamics has remained elusive. Here, we dissect shared and divergent functions of Pax6 during amniote brain development. Comparative functional analyses revealed that the neurogenic function of Pax6 is highly conserved in the developing mouse and chick pallium, whereas stage-specific binary functions of Pax6 in neurogenesis are unique to mouse neuronal progenitors, consistent with Pax6-dependent temporal regulation of Notch signaling. Furthermore, we identified that Pax6-dependent enhancer activity of Dbx1 is extensively conserved between mammals and chick, although Dbx1 expression in the developing pallium is highly divergent in these species. Our results suggest that spatiotemporal changes in Pax6-dependent regulatory programs contributed to species-specific neurogenic patterns in mammalian and avian lineages, which underlie the morphological divergence of the amniote pallial architectures.

Highlights

The evolution of animal body structures is accomplished by pronounced changes in conserved developmental programs
Genome editing in chick brain reveals conserved functions of Pax6 in neurogenesis We chose Pax6 for the analyses of conserved and derived roles of homologous transcription factors (TFs) in species-specific brain development because (1) the protein structures and expression patterns of Pax6 are extremely highly conserved among species, (2) other genes with compensatory functions are not expressed in the developing pallium, and (3) downstream target genes have been wellcharacterized in the developing mouse neocortex
In the developing mouse and chick pallium, Pax6 is highly expressed in the ventricular zone (VZ) neural progenitors [radial glial cells (RGCs)], the progenitor compositions and characteristics are not identical in these species (Fig. 1A,B)

Summary

Introduction

The evolution of animal body structures is accomplished by pronounced changes in conserved developmental programs. The dorsal part of the telencephalon (the pallium) gives rise to species-specific architecture: the mammalian pallium elaborates the neocortex, which is characterized by horizontal expansion of surface area and a six-layered laminar organization (Nieuwenhuys, 1994) These anatomical hallmarks of the neocortex are constructed by the spatial and temporal regulation of neural progenitor proliferation and differentiation in the developing dorsal pallium; regional and chronological expression of core regulatory genes tightly control the amplification of neural progenitors in the ventricular zone (VZ) and subventricular zone (SVZ) and the sequential production of layerspecific neurons (Götz and Huttner, 2005; Kriegstein et al, 2006). Reptiles and birds have a dorsal ventricular ridge, which is a prominent tissue protrusion at the lateral wall of the cerebral hemisphere, as a derivative of the ventral pallium (VP) (Ulinski, 1983) These morphological differences might be provided by species-specific patterns of progenitor proliferation and neuronal specification in distinct sectors of the embryonic pallium (Suzuki et al, 2012; Nomura et al, 2013; García-Moreno and Molnár, 2015)

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Conclusion