Cephalopod Retinal Development Shows Vertebrate-like Mechanisms of Neurogenesis

Abstract

Neurogenesis, the regulation of cellular proliferation and differentiation in the developing nervous system, is the process that underlies the diversity of size and cell type found in animal nervous systems. Our understanding of how this process has evolved is limited because of the lack of high resolution data and live-imaging methods across species. The retina is a classic model for the study of neurogenesis in vertebrates and live-imaging of the retina has shown that during development, progenitor cells are organized in a pseudostratified neuroepithelium and nuclei migrate in coordination with the cell cycle along the apicobasal axis of the cell, a process called interkinetic nuclear migration. Eventually cells delaminate and differentiate within the boundaries of the epithelium. This process has been considered unique to vertebrates and thought to be important in maintaining organization during the development of a complex nervous system. Coleoid cephalopods, including squid, cuttlefish and octopus, have the largest nervous system of any invertebrate and convergently-evolved camera-type eyes, making them a compelling comparative system to vertebrates. Here we have pioneered live-imaging techniques to show that the squid, Doryteuthis pealeii, displays cellular mechanisms during cephalopod retinal neurogenesis that are hallmarks of vertebrate processes. We find that retinal progenitor cells in the squid undergo interkinetic nuclear migration until they exit the cell cycle, we identify retinal organization corresponding to progenitor, post-mitotic and differentiated cells, and we find that Notch signaling regulates this process. With cephalopods and vertebrates having diverged 550 million years ago, these results suggest that mechanisms thought to be unique to vertebrates may be common to highly proliferative neurogenic primordia contributing to a large nervous system.

A single-cell atlas of bobtail squid visual and nervous system highlights molecular principles of convergent evolution

“…Expression of r-opsin1 mRNA is detected by HCR below the basement membrane suggesting that these cells may occupy a more proximal location in the retina (Figure 2D-D’’). Finally, a small Musashi+ population (‘Photoreceptor_undiff’) also expresses Sy65 and phototransduction markers (but not RABP), as well as an ephrin receptor Epha7 which has been described as a marker of developing photoreceptors in other cephalopod species (Napoli et al, 2021). We hypothesize that Photoreceptor_r1 and Photoreceptor_undiff populations could correspond to different steps in the photoreceptor maturation process.…”

“…The squid retina also contains a pigmented cell population (‘Pigmented2’) that is positive for phototransduction genes but negative for neuronal marker Sy65 (Figure S3C). This cell type likely corresponds to the pigmented support cells embedded below the basement membrane of the retina (Koenig et al, 2016; Napoli et al, 2021; Wentworth and Muntz, 1992; Yamamoto and Takasu, 1984; Yamamoto et al, 1965; Young, 1971). These cell types are intermingled in the retina as schematized in Figure 2H and can be readily identified on corresponding EM sections (Figure 2H).…”