PT  - JOURNAL ARTICLE
AU  - Elena F. Boer
AU  - Hannah F. Van Hollebeke
AU  - Sungdae Park
AU  - Carlos R. Infante
AU  - Douglas B. Menke
AU  - Michael D. Shapiro
TI  - Pigeon foot feathering reveals conserved limb identity networks
AID  - 10.1101/602987
DP  - 2019 Jan 01
TA  - bioRxiv
PG  - 602987
4099  - http://biorxiv.org/content/early/2019/04/09/602987.short
4100  - http://biorxiv.org/content/early/2019/04/09/602987.full
AB  - The tetrapod limb is a stunning example of evolutionary diversity, with dramatic variation not only among distantly related species, but also between the serially homologous forelimbs (FLs) and hindlimbs (HLs) within species. Despite this variation, highly conserved genetic and developmental programs underlie limb development and identity in all tetrapods, raising the question of how limb diversification is generated from a conserved toolkit. In some breeds of domestic pigeon, shifts in the expression of two conserved limb identity transcription factors, PITX1 and TBX5, are associated with the formation of feathered HLs with partial FL identity. To determine how modulation of PITX1 and TBX5 expression affects downstream gene expression, we compared the transcriptomes of embryonic limb buds from pigeons with scaled and feathered HLs. We identified a set of differentially expressed genes enriched for genes encoding transcription factors, extracellular matrix proteins, and components of developmental signaling pathways with important roles in limb development. A subset of the genes that distinguish scaled and feathered HLs are also differentially expressed between FL and scaled HL buds in pigeons, pinpointing a set of gene expression changes downstream of PITX1 and TBX5 in the partial transformation from HL to FL identity. We extended our analyses by comparing pigeon limb bud transcriptomes to chicken, anole lizard, and mammalian datasets to identify deeply conserved PITX1- and TBX5-regulated components of the limb identity program. Our analyses reveal a suite of predominantly low-level gene expression changes that are conserved across amniotes to regulate the identity of morphologically distinct limbs.Summary statement In feather-footed pigeons, mutant alleles of PITX1 and TBX5 drive the partial redeployment of an evolutionarily conserved forelimb genetic program in the hindlimb.