title: Transcriptomic and epigenomic characterization of the developing bat wing.
abstract: Bats are the only mammals capable of powered flight, but little is known about the genetic determinants that shape their wings. Here we generated a genome for Miniopterus natalensis and performed RNA-seq and ChIP-seq (H3K27ac and H3K27me3) analyses on its developing forelimb and hindlimb autopods at sequential embryonic stages to decipher the molecular events that underlie bat wing development. Over 7,000 genes and several long noncoding RNAs, including Tbx5-as1 and Hottip, were differentially expressed between forelimb and hindlimb, and across different stages. ChIP-seq analysis identified thousands of regions that are differentially modified in forelimb and hindlimb. Comparative genomics found 2,796 bat-accelerated regions within H3K27ac peaks, several of which cluster near limb-associated genes. Pathway analyses highlighted multiple ribosomal proteins and known limb patterning signaling pathways as differentially regulated and implicated increased forelimb mesenchymal condensation in differential growth. In combination, our work outlines multiple genetic components that likely contribute to bat wing formation, providing insights into this morphological innovation.
authors.affiliation: Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, San Francisco, California, USA.|Institute for Human Genetics, University of California, San Francisco, San Francisco, California, USA.
authors.forename: Walter L
authors.initials: WL
authors.lastname: Eckalbar
authors.affiliation: Department of Molecular and Cell Biology, University of Cape Town, Cape Town, South Africa.
authors.forename: Stephen A
authors.initials: SA
authors.lastname: Schlebusch
authors.affiliation: Department of Molecular and Cell Biology, University of Cape Town, Cape Town, South Africa.
authors.forename: Mandy K
authors.initials: MK
authors.lastname: Mason
authors.affiliation: Department of Molecular and Cell Biology, University of Cape Town, Cape Town, South Africa.
authors.forename: Zoe
authors.initials: Z
authors.lastname: Gill
authors.affiliation: Department of Molecular and Cell Biology, University of Cape Town, Cape Town, South Africa.
authors.forename: Ash V
authors.initials: AV
authors.lastname: Parker
authors.affiliation: Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, San Francisco, California, USA.|Institute for Human Genetics, University of California, San Francisco, San Francisco, California, USA.
authors.forename: Betty M
authors.initials: BM
authors.lastname: Booker
authors.affiliation: Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, San Francisco, California, USA.|Institute for Human Genetics, University of California, San Francisco, San Francisco, California, USA.
authors.forename: Sierra
authors.initials: S
authors.lastname: Nishizaki
authors.affiliation: Department of Molecular and Cell Biology, University of Cape Town, Cape Town, South Africa.
authors.forename: Christiane
authors.initials: C
authors.lastname: Muswamba-Nday
authors.affiliation: Oregon National Primate Research Center, Division of Neuroscience, Primate Genetics Section, Beaverton, Oregon, USA.|Department of Molecular, Cellular and Developmental Biology, University of Colorado, Boulder, Colorado, USA.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Terhune
authors.affiliation: Oregon National Primate Research Center, Division of Neuroscience, Primate Genetics Section, Beaverton, Oregon, USA.
authors.forename: Kimberly A
authors.initials: KA
authors.lastname: Nevonen
authors.affiliation: Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, San Francisco, California, USA.|Institute for Human Genetics, University of California, San Francisco, San Francisco, California, USA.
authors.forename: Nadja
authors.initials: N
authors.lastname: Makki
authors.affiliation: Institute for Human Genetics, University of California, San Francisco, San Francisco, California, USA.|Gladstone Institutes, San Francisco, California, USA.
authors.forename: Tara
authors.initials: T
authors.lastname: Friedrich
authors.affiliation: Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, San Francisco, California, USA.|Institute for Human Genetics, University of California, San Francisco, San Francisco, California, USA.
authors.forename: Julia E
authors.initials: JE
authors.lastname: VanderMeer
authors.affiliation: Institute for Human Genetics, University of California, San Francisco, San Francisco, California, USA.|Gladstone Institutes, San Francisco, California, USA.|Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, California, USA.
authors.forename: Katherine S
authors.initials: KS
authors.lastname: Pollard
authors.affiliation: Oregon National Primate Research Center, Division of Neuroscience, Primate Genetics Section, Beaverton, Oregon, USA.|Department of Behavioral Neuroscience, Oregon Health and Science University, Portland, Oregon, USA.
authors.forename: Lucia
authors.initials: L
authors.lastname: Carbone
authors.affiliation: Institute for Human Genetics, University of California, San Francisco, San Francisco, California, USA.|Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, California, USA.
authors.forename: Jeff D
authors.initials: JD
authors.lastname: Wall
authors.affiliation: Department of Molecular and Cell Biology, University of Cape Town, Cape Town, South Africa.
authors.forename: Nicola
authors.initials: N
authors.lastname: Illing
authors.affiliation: Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, San Francisco, California, USA.|Institute for Human Genetics, University of California, San Francisco, San Francisco, California, USA.
authors.forename: Nadav
authors.initials: N
authors.lastname: Ahituv
mesh_terms: D000818:Animals; D002685:Chiroptera / Q000196:embryology* / Q000235:genetics*; D047108:Embryonic Development / Q000235:genetics; D044127:Epigenesis, Genetic; D020869:Gene Expression Profiling; D016678:Genome; D008297:Male; D062085:RNA, Long Noncoding; D012045:Regulatory Sequences, Nucleic Acid; D017423:Sequence Analysis, RNA; D059467:Transcriptome; D014921:Wings, Animal / Q000196:embryology*
chemical_list: D062085:RNA, Long Noncoding