Unique expression patterns of multiple key genes associated with the evolution of mammalian flight

Abstract

Bats are the only mammals capable of true flight. Critical adaptations for flight include a pair of dramatically elongated hands with broad wing membranes. To study the molecular mechanisms of bat wing evolution, we perform genomewide mRNA sequencing and in situ hybridization for embryonic bat limbs. We identify seven key genes that display unique expression patterns in embryonic bat wings and feet, compared with mouse fore- and hindlimbs. The expression of all 5′HoxD genes ( Hoxd9–13 ) and Tbx3 , six known crucial transcription factors for limb and digit development, is extremely high and prolonged in the elongating wing area. The expression of Fam5c , a tumour suppressor, in bat limbs is bat-specific and significantly high in all short digit regions (the thumb and foot digits). These results suggest multiple genetic changes occurred independently during the evolution of bat wings to elongate the hand digits, promote membrane growth and keep other digits short. Our findings also indicate that the evolution of limb morphology depends on the complex integration of multiple gene regulatory networks and biological processes that control digit formation and identity, chondrogenesis, and interdigital regression or retention.

Timing the developmental origins of mammalian limb diversity

“…), Fgf8, and Shh in bat fore-and hind limbs (Eckalbar et al, 2016;Maier et al, 2017;Wang et al, 2014), and of Bmp's and associated genes in developing bat digits of differing lengths (Eckalbar et al, 2016;Maier et al, 2017;Wang et al, 2010). These assays largely support the results of previous candidate gene approaches.…”

Transcriptomic insights into the genetic basis of mammalian limb diversity

“…For example, through the morphological diversification of their limbs, mammals were able to infiltrate almost every habitat in the world, and exhibit a wide-range of feeding and social behaviors [13]. To date, studies of mammalian limb evolution and development has been limited mostly to investigations of the role of candidate genes (e.g., bats [3, 11, 12, 16–19], whales [4], opossums [20–23], non-cetacean artiodactyls [8], jerboas [8]), or, in a couple of cases, transcriptomes [24–27], in individual species. From these studies we have learned that mammalian limb diversification has proceeded not by major changes to limb structure (e.g., complete loss or gain of entire segments), but by the modification of segments inherited from their generalized, pentadactyl ancestor [28, 29].…”

Homology of the chiropteran “dactylopatagium” brevis

“…the brevis section, seems to have a separate origin. The pattern of expression of other genes in the wing membrane (the T-Box Transcription Factor gene TBX3, the homeobox HOXD), the perichondrium of elongate digits (Hoxd), and the tip of digits (the family with sequence similarity 5, member C gene FAM5C) also exhibit contrasting expression patterns between membrane areas around elongate digits II to V versus the thumb area (Wang et al, 2014).…”

“…BMP2 promotes programmed cell death (apoptosis) but its action is prevented by its antagonists, GRE and FGF8, such that the interdigital tissue survives and becomes the handwing membrane (Weatherbee et al, 2006). The wing membrane around the thumb is not affected in the same way because GRE and FGF8 are strongly AP-patterned and only poorly traced in this small area (Hockman et al, 2008;Wang et al, 2014), so their effect on preventing apoptosis via BMP inhibition is deduced to be minimal and most of the corresponding embryonic tissue is lost. Thus, A c c e p t e d M a n u s c r i p t the membrane next to the thumb, i.e.…”