Tetrapod limb and sarcopterygian fin regeneration share a core genetic programme.
Salamanders are the only living tetrapods capable of fully regenerating limbs. The discovery of salamander lineage-specific genes (LSGs) expressed during limb regeneration suggests that this capacity is a salamander novelty. Conversely, recent paleontological evidence supports a deeper evolutionary origin, before the occurrence of salamanders in the fossil record. Here we show that lungfishes, the sister group of tetrapods, regenerate their fins through morphological steps equivalent to those seen in salamanders. Lungfish de novo transcriptome assembly and differential gene expression analysis reveal notable parallels between lungfish and salamander appendage regeneration, including strong downregulation of muscle proteins and upregulation of oncogenes, developmental genes and lungfish LSGs. MARCKS-like protein (MLP), recently discovered as a regeneration-initiating molecule in salamander, is likewise upregulated during early stages of lungfish fin regeneration. Taken together, our results lend strong support for the hypothesis that tetrapods inherited a bona fide limb regeneration programme concomitant with the fin-to-limb transition.
Instituto de Ciências Biológicas, Universidade Federal do Pará, Rua Augusto Correa, 01, Belém 66075-110, Brazil.
Acacio F
AF
Nogueira
Instituto de Ciências Biológicas, Universidade Federal do Pará, Rua Augusto Correa, 01, Belém 66075-110, Brazil.
Carinne M
CM
Costa
Instituto de Ciências Biológicas, Universidade Federal do Pará, Rua Augusto Correa, 01, Belém 66075-110, Brazil.
Jamily
J
Lorena
Instituto de Ciências Biológicas, Universidade Federal do Pará, Rua Augusto Correa, 01, Belém 66075-110, Brazil.
Rodrigo N
RN
Moreira
Instituto de Ciências Biológicas, Universidade Federal do Pará, Rua Augusto Correa, 01, Belém 66075-110, Brazil.
Gabriela N
GN
Frota-Lima
Unidade Genômica, Programa de Genética, Instituto Nacional do Câncer, Rio de Janeiro 20230-240, Brazil.
Carolina
C
Furtado
Benaroya Research Institute at Virginia Mason, 1201 Ninth Avenue, Seattle, Washington 98101, USA.
Mark
0000-0002-4153-1313
M
Robinson
Benaroya Research Institute at Virginia Mason, 1201 Ninth Avenue, Seattle, Washington 98101, USA.|Department of Biology, University of Washington 106 Kincaid, Seattle, Washington 98195, USA.
Chris T
CT
Amemiya
Instituto de Ciências Biológicas, Universidade Federal do Pará, Rua Augusto Correa, 01, Belém 66075-110, Brazil.
Sylvain
0000-0001-6351-0903
S
Darnet
Instituto de Ciências Biológicas, Universidade Federal do Pará, Rua Augusto Correa, 01, Belém 66075-110, Brazil.
Igor
I
Schneider
D000595:Amino Acid Sequence; D058500:Animal Fins / Q000033:anatomy & histology / Q000502:physiology*; D000818:Animals; D005121:Extremities / Q000502:physiology*; D029941:Fish Proteins / Q000737:chemistry / Q000378:metabolism; D005399:Fishes / Q000235:genetics* / Q000502:physiology*; D018507:Gene Expression Regulation, Developmental; D010802:Phylogeny; D012038:Regeneration / Q000502:physiology*; D015854:Up-Regulation / Q000235:genetics
D029941:Fish Proteins