Abstract

Neurons and pancreatic endocrine cells have a common physiology and express a similar toolkit of transcription factors during development. To explain these common features, it has been hypothesized that pancreatic cells most likely co-opted a pre-existing gene regulatory program from ancestral neurons. To test this idea, we looked for neurons with a “pre-pancreatic” program in an early-branched deuterostome, the sea urchin. Only vertebrates have a proper pancreas, however, our lab previously found that cells with a pancreatic-like signature are localized within the sea urchin embryonic gut. We also found that the pancreatic transcription factors Xlox/Pdx1 and Brn1/2/4 co-localize in a sub-population of ectodermal cells. Here, we find that the ectodermal SpLox+ SpBrn1/2/4 cells are specified as SpSoxC and SpPtf1a neuronal precursors that become the lateral ganglion and the apical organ neurons. Two of the SpLox+ SpBrn1/2/4 cells also express another pancreatic transcription factor, the LIM-homeodomain gene islet-1. Moreover, we find that SpLox neurons produce the neuropeptide SpANP2, and that SpLox regulates SpANP2 expression. Taken together, our data reveal that there is a subset of sea urchin larval neurons with a gene program that predated pancreatic cells. These findings suggest that pancreatic endocrine cells co-opted a regulatory signature from an ancestral neuron that was already present in an early-branched deuterostome.

Highlights

  • Complex organisms have more cell types than structurally simple ones

  • Pancreatic endocrine β-cells and neurons are an example of different cell types that share a similar gene program but exert different functions

  • In order to identify terminal differentiation genes of the SpLox neurons, we looked at the expression of the sea urchin neuropeptides described by Woods et al and Rowe et al [54]

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Summary

Introduction

Functionally distinct cell types show remarkably similar gene programs. This shared program can be the result of a common evolutionary ancestor cell or of convergent evolution. Pancreatic endocrine β-cells and neurons are an example of different cell types that share a similar gene program but exert different functions. These two cell types share many remarkable features [1,2,3,4,5,6,7]. Many genes expressed in neuronal development are expressed in the development of pancreatic β-cells [7], like the homeodomain protein Isl1 [9], the bHLH transcription factors neurogenins [10,11,12], and the homeobox transcription factor PDX1 [13, 14]

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