Recurrent DCC gene losses during bird evolution

François Friocourt,Anne-Gaelle Lafont,Alain Chédotal,Bertrand Pain,Clémence Kress,Marie Manceau,Sylvie Dufour

doi:10.1038/srep37569

Abstract

During development, midline crossing by axons brings into play highly conserved families of receptors and ligands. The interaction between the secreted ligand Netrin-1 and its receptor Deleted in Colorectal Carcinoma (DCC) is thought to control midline attraction of crossing axons. Here, we studied the evolution of this ligand/receptor couple in birds taking advantage of a wealth of newly sequenced genomes. From phylogeny and synteny analyses we can infer that the DCC gene has been conserved in most extant bird species, while two independent events have led to its loss in two avian groups, passeriformes and galliformes. These convergent accidental gene loss events are likely related to chromosome Z rearrangement. We show, using whole-mount immunostaining and 3Disco clearing, that in the nervous system of all birds that have a DCC gene, DCC protein expression pattern is similar to other vertebrates. Surprisingly, we show that the early developmental pattern of commissural tracts is comparable in all birds, whether or not they have a DCC receptor. Interestingly, only 4 of the 5 genes encoding secreted netrins, the DCC ligands in vertebrates, were found in birds, but Netrin-5 was absent. Together, these results support a remarkable plasticity of commissural axon guidance mechanisms in birds.

Highlights

Despite more than 600 million years of evolution, the basic components of the bilaterian brain wiring diagram are highly conserved 1
Deleted in Colorectal Carcinoma (DCC) gene is present in most sauropsid genomes We first investigated whether a DCC gene is present in all available sauropsid genomes
We found DCC genes in representative species of saurians, chelonians, crocodilians, as well as in many bird species, including paleognathes, anseriformes and numerous neoaves

Summary

Introduction

Despite more than 600 million years of evolution, the basic components of the bilaterian brain wiring diagram are highly conserved 1. The vertebrate DCC gene (Deleted in Colorectal Carcinoma 12), and its homologues in C.elegans 13 and Drosophila 14, encode a transmembrane receptor, mediating Netrin-1 attraction. In these species, DCC loss-of-function prevents many commissural axons from crossing the midline, thereby supporting DCC pivotal role in midline guidance [14,15]. The in ovo electroporation of dominant negative constructs of DCC or DCC signaling partners in the chick spinal cord significantly perturbs commissural and motor axon guidance [21,22,23] This suggests that a DCC gene might exist in the chick genome, which is known to be fragmented and to contain at least 30 microchromosomes 24. We have performed a comparative analysis of the organization and development of commissural circuits in early bird embryos

Methods

Results

Conclusion