{"id":8269,"date":"2016-03-31T10:49:45","date_gmt":"2016-03-31T10:49:45","guid":{"rendered":"http:\/\/revoscience.com\/en\/?p=8269"},"modified":"2016-03-31T10:49:45","modified_gmt":"2016-03-31T10:49:45","slug":"researchers-learn-how-the-bat-got-its-wings","status":"publish","type":"post","link":"https:\/\/www.revoscience.com\/en\/researchers-learn-how-the-bat-got-its-wings\/","title":{"rendered":"Researchers Learn How The Bat Got Its Wings"},"content":{"rendered":"<figure id=\"attachment_8270\" aria-describedby=\"caption-attachment-8270\" style=\"width: 239px\" class=\"wp-caption alignright\"><a href=\"http:\/\/revoscience.com\/en\/wp-content\/uploads\/2016\/03\/bt1603_ucsf_batwing.jpg\" target=\"_blank\" rel=\"noopener\"><img loading=\"lazy\" decoding=\"async\" class=\"wp-image-8270 size-medium\" src=\"http:\/\/revoscience.com\/en\/wp-content\/uploads\/2016\/03\/bt1603_ucsf_batwing-239x300.jpg\" alt=\"Natal long-fingered bat embryo (Miniopterus natalensis) stained to highlight bone (red) and cartilage (blue). (Photo: Mandy K. Mason\/University of Cape Town)\" width=\"239\" height=\"300\" title=\"\" srcset=\"https:\/\/www.revoscience.com\/en\/wp-content\/uploads\/2016\/03\/bt1603_ucsf_batwing-239x300.jpg 239w, https:\/\/www.revoscience.com\/en\/wp-content\/uploads\/2016\/03\/bt1603_ucsf_batwing.jpg 370w\" sizes=\"auto, (max-width: 239px) 100vw, 239px\" \/><\/a><figcaption id=\"caption-attachment-8270\" class=\"wp-caption-text\">Natal long-fingered bat embryo (Miniopterus natalensis) stained to highlight bone (red) and cartilage (blue). (Photo: Mandy K. Mason\/University of Cape Town)<\/figcaption><\/figure>\n<p style=\"text-align: justify;\"><span style=\"color: #000000;\">An international team of scientists, including groups from UC San Francisco, Gladstone Institutes, and the University of Cape Town (UCT), South Africa, have for the first time identified genes and gene regulatory elements that are essential in wing development in the Natal long-fingered bat (Miniopterus natalensis), a species widely distributed in eastern and southern Africa.<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"color: #000000;\">The new research \u2014 presented in two papers published on one in\u00a0<em>Nature Genetics<\/em>\u00a0and one in\u00a0<em>PLoS Genetics<\/em>\u2014 revealed regulatory switches that turn bat genes on and off at crucial times during limb development, and has implications for understanding how differences in the size, shape and structure of limbs are generated in mammals in general, including humans, the researchers said.<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"color: #000000;\">\u201cThis gives us our first detailed picture of the genomics behind bat wing development,\u201d said co-senior investigator Nadav Ahituv, Ph.D., a UCSF associate professor of bioengineering and therapeutic sciences in the UCSF School of Pharmacy and member of the UCSF Institute for Human Genetics, whose lab also studies the genetics of human limb malformations. \u201cWhile some attempts have been made to identify the molecular events that led to the evolution of the bat wing, these have been primarily done on a \u2018gene by gene\u2019 basis. In contrast, this work lays out a genome-wide blueprint for the causes that led to the development of the bat wing, a key evolutionary innovation that contributed to bats becoming the second most diverse order of mammals.\u201d<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"color: #000000;\">Bats are the only mammals capable of powered flight \u2014 an innovation that is thought to have occurred about 50 million years ago. Biologists since Charles Darwin have used the structure of the bat wing as an example of both evolutionary novelty \u2014 the appearance of a new trait \u2014 and vertebrate homology, or shared ancestry between two seemingly different structures \u2014 in this case, the wing of the bat and the forelimb of other mammals. But the path of bats\u2019 unique evolution is unclear, noted Nicola Illing, Ph.D., co-senior investigator in the Department of Molecular and Cell Biology at UCT.<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"color: #000000;\">\u201cThe fossil record does not show the transition from tree-climbing mammals with short, free digits to ones that have elongated fingers supporting a wing,\u201d Illing said. \u201cUntil now, scientists knew very little about how genes are turned on and off during bat embryonic development to transform a mammalian forelimb into a wing.\u201d<\/span><\/p>\n<p style=\"text-align: justify;\">[pullquote]The researchers identified over 7,000 genes that are expressed differently in forelimbs compared with hindlimbs at three key stages of bat wing development.[\/pullquote]<\/p>\n<p style=\"text-align: justify;\"><span style=\"color: #000000;\">In the\u00a0<em>Nature Genetics<\/em>\u00a0paper, the scientists, including co-lead authors Walter L. Eckalbar, Ph.D., a postdoctoral fellow in Ahituv\u2019s laboratory at UCSF, and Ph.D. student Stephen Schlebusch of UCT, first sequenced the entire genome of the Natal long-fingered bat. They then performed detailed molecular genomic analysis on bat embryos collected by Illing and her research group at the de Hoop Nature Reserve in South Africa.<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"color: #000000;\">The researchers identified over 7,000 genes that are expressed differently in forelimbs compared with hindlimbs at three key stages of bat wing development. They found that many signaling pathways are activated differentially as well, including pathways important in limb formation, digit growth, long bone development and cell death. Also expressed differently are many proteins associated with ribosomes \u2013 molecular machines found in all cells that are responsible for protein production during limb development.<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"color: #000000;\">\u201cIt took bats millions of years to evolve wings,\u201d said Eckalbar. \u201cOur work shows that they did this through thousands of genetic alterations, involving both genes used by all animals during limb development and genes whose usage in limb development may be unique to bats.\u201d<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"color: #000000;\">In addition, the scientists found thousands of genetic switches, called enhancers, which regulate the timing and levels of gene expression and show differences in activity between forelimbs and hindlimbs at these key stages of wing development.<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"color: #000000;\">\u201cImportantly, this work identified not just which genes are expressed at what stage of growth, but the genetic switches in the genome that are responsible for turning those genes on and off,\u201d Ahituv said.<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"font-weight: bold; color: #000000;\">Researchers map bat wings\u2019 unique evolutionary origins<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"color: #000000;\">In the study published in\u00a0<em>PLoS Genetics<\/em>, the research team, including co-lead authors Betty M. Booker, Ph.D., a post-doctoral fellow in Ahituv\u2019s laboratory, and Tara Friedrich, a Ph.D. student at UCSF and Gladstone Institutes, searched for the evolutionary origin of the bat wing.<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"color: #000000;\">\u201cWe identified genomic sequences that have not changed in most vertebrates, but experienced rapid changes in the common ancestor of today\u2019s bats,\u201d explained Friedrich, a member of the laboratory of co-senior investigator Katherine S. Pollard, Ph.D., a senior investigator at the Gladstone Institutes, a UCSF professor of epidemiology and biostatistics, and a member of the UCSF Institute for Human Genetics.<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"color: #000000;\">The team mapped these so-called \u201cbat accelerated regions\u201d (BARs) onto areas that were predicted to be important switches that turn genes on during limb development, and found 166 BARs with the potential to influence bat wing development.<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"color: #000000;\">The researchers tested the effects of five of these BARs in genetically modified mouse embryos and found that all five bat sequences were capable of switching on a reporter gene in the developing mouse forelimb. They noted that one region, BAR116, is located near the HoxD genes, which are known to be involved in limb patterning and skeletal growth.<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"color: #000000;\">Previously, Mandy Mason, a Ph.D. student at UCT, had shown that two of the HoxD genes \u2014 Hoxd10 and Hoxd11 \u2014 are far more active in bat wings compared to bat legs during their embryonic development. Following up these lines of evidence, the researchers showed that the bat BAR116 sequence appears to function as a genetic switch that is active in developing limbs, in particular the forelimbs, while the equivalent mouse sequence did not show any activity.<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"color: #000000;\">\u201cOur computational method enabled identification of DNA sequences that changed dramatically during the emergence of bats,\u201d said Pollard. \u201cIt is exciting to see that this evolutionary signature pointed us to parts of the mammalian genome that control limb development.\u201d<\/span><\/p>\n<p style=\"text-align: justify;\"><span style=\"color: #000000;\">In addition to unveiling new fundamental details of the evolutionary and developmental origins of powered flight in bats, the new research may provide broader insights into the biological processes that control how mammalian limbs develop in general, Ahituv said. \u201cImportantly, this work will increase our understanding of how alterations in limb development could lead to limb malformations in humans,\u201d he said. \u201cPotentially, it could eventually help contribute to the development of tools and techniques to prevent such malformations.\u201d<\/span><\/p>\n","protected":false},"excerpt":{"rendered":"<p>An international team of scientists, including groups from UC San Francisco, Gladstone Institutes, and the University of Cape Town (UCT), South Africa, have for the first time identified genes and gene regulatory elements that are essential in wing development in the Natal long-fingered bat.<\/p>\n","protected":false},"author":6,"featured_media":8270,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[16,17],"tags":[],"class_list":["post-8269","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-biology","category-research"],"featured_image_urls":{"full":["https:\/\/www.revoscience.com\/en\/wp-content\/uploads\/2016\/03\/bt1603_ucsf_batwing.jpg",370,463,false],"thumbnail":["https:\/\/www.revoscience.com\/en\/wp-content\/uploads\/2016\/03\/bt1603_ucsf_batwing-150x150.jpg",150,150,true],"medium":["https:\/\/www.revoscience.com\/en\/wp-content\/uploads\/2016\/03\/bt1603_ucsf_batwing-239x300.jpg",239,300,true],"medium_large":["https:\/\/www.revoscience.com\/en\/wp-content\/uploads\/2016\/03\/bt1603_ucsf_batwing.jpg",370,463,false],"large":["https:\/\/www.revoscience.com\/en\/wp-content\/uploads\/2016\/03\/bt1603_ucsf_batwing.jpg",370,463,false],"1536x1536":["https:\/\/www.revoscience.com\/en\/wp-content\/uploads\/2016\/03\/bt1603_ucsf_batwing.jpg",370,463,false],"2048x2048":["https:\/\/www.revoscience.com\/en\/wp-content\/uploads\/2016\/03\/bt1603_ucsf_batwing.jpg",370,463,false],"ultp_layout_landscape_large":["https:\/\/www.revoscience.com\/en\/wp-content\/uploads\/2016\/03\/bt1603_ucsf_batwing.jpg",370,463,false],"ultp_layout_landscape":["https:\/\/www.revoscience.com\/en\/wp-content\/uploads\/2016\/03\/bt1603_ucsf_batwing.jpg",370,463,false],"ultp_layout_portrait":["https:\/\/www.revoscience.com\/en\/wp-content\/uploads\/2016\/03\/bt1603_ucsf_batwing.jpg",370,463,false],"ultp_layout_square":["https:\/\/www.revoscience.com\/en\/wp-content\/uploads\/2016\/03\/bt1603_ucsf_batwing.jpg",370,463,false],"newspaper-x-single-post":["https:\/\/www.revoscience.com\/en\/wp-content\/uploads\/2016\/03\/bt1603_ucsf_batwing.jpg",370,463,false],"newspaper-x-recent-post-big":["https:\/\/www.revoscience.com\/en\/wp-content\/uploads\/2016\/03\/bt1603_ucsf_batwing.jpg",288,360,false],"newspaper-x-recent-post-list-image":["https:\/\/www.revoscience.com\/en\/wp-content\/uploads\/2016\/03\/bt1603_ucsf_batwing.jpg",52,65,false],"web-stories-poster-portrait":["https:\/\/www.revoscience.com\/en\/wp-content\/uploads\/2016\/03\/bt1603_ucsf_batwing.jpg",370,463,false],"web-stories-publisher-logo":["https:\/\/www.revoscience.com\/en\/wp-content\/uploads\/2016\/03\/bt1603_ucsf_batwing.jpg",77,96,false],"web-stories-thumbnail":["https:\/\/www.revoscience.com\/en\/wp-content\/uploads\/2016\/03\/bt1603_ucsf_batwing.jpg",150,188,false]},"author_info":{"info":["Amrita Tuladhar"]},"category_info":"<a href=\"https:\/\/www.revoscience.com\/en\/category\/news\/biology\/\" rel=\"category tag\">Biology<\/a> <a href=\"https:\/\/www.revoscience.com\/en\/category\/news\/research\/\" rel=\"category 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