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clifford AND tabin

Katherine D Walton, Darcy Mishkind, Misty R Riddle, Clifford J Tabin, Deborah L Gumucio
Efficient absorption of nutrients by the intestine is essential for life. In mammals and birds, convolution of the intestinal surface into finger-like projections called villi is an important adaptation that ensures the massive surface area for nutrient contact that is required to meet metabolic demands. Each villus projection serves as a functional absorptive unit: it is covered by a simple columnar epithelium that is derived from endoderm and contains a mesodermally derived core with supporting vasculature, lacteals, enteric nerves, smooth muscle, fibroblasts, myofibroblasts, and immune cells...
March 7, 2018: Wiley Interdisciplinary Reviews. Developmental Biology
Tom W Hiscock, Patrick Tschopp, Clifford J Tabin
Critical steps in forming the vertebrate limb include the positioning of digits and the positioning of joints within each digit. Recent studies have proposed that the iterative series of digits is established by a Turing-like mechanism generating stripes of chondrogenic domains. However, re-examination of available data suggest that digits are actually patterned as evenly spaced spots, not stripes, which then elongate into rod-shaped digit rays by incorporating new cells at their tips. Moreover, extension of the digit rays and the patterning of the joints occur simultaneously at the distal tip, implying that an integrated model is required to fully understand these processes...
June 5, 2017: Developmental Cell
Abigail R Wark, Elizabeth J Terman, Clifford J Tabin
MicroRNAs are endogenous, regulatory RNAs implicated in many biological processes including pigmentation. Software algorithms and in vitro experiments predict that microRNAs can target pigmentation pathway genes, but few have been tested in vivo. MiR-128-1, a microRNA within the strongly selected lactase locus in the human genome, has predicted pigmentation targets. To test the role of miR-128-1 in pigment regulation, we created C57BL/6 agouti miR-128-1 knockout mice and quantified melanin deposition in hair...
April 18, 2017: Experimental Dermatology
Alan R Rodrigues, Nayuta Yakushiji-Kaminatsui, Yuji Atsuta, Guillaume Andrey, Patrick Schorderet, Denis Duboule, Clifford J Tabin
During embryonic development, fields of progenitor cells form complex structures through dynamic interactions with external signaling molecules. How complex signaling inputs are integrated to yield appropriate gene expression responses is poorly understood. In the early limb bud, for instance, Sonic hedgehog (Shh) is expressed in the distal posterior mesenchyme, where it acts as a mediator of anterior to posterior (AP) patterning, whereas fibroblast growth factor 8 (Fgf8) is produced by the apical ectodermal ridge (AER) at the distal tip of the limb bud to direct outgrowth along the proximal to distal (PD) axis...
March 21, 2017: Proceedings of the National Academy of Sciences of the United States of America
Nandan L Nerurkar, L Mahadevan, Clifford J Tabin
Looping of the initially straight embryonic gut tube is an essential aspect of intestinal morphogenesis, permitting proper placement of the lengthy small intestine within the confines of the body cavity. The formation of intestinal loops is highly stereotyped within a given species and results from differential-growth-driven mechanical buckling of the gut tube as it elongates against the constraint of a thin, elastic membranous tissue, the dorsal mesentery. Although the physics of this process has been studied, the underlying biology has not...
February 28, 2017: Proceedings of the National Academy of Sciences of the United States of America
Donald M Bryant, Kimberly Johnson, Tia DiTommaso, Timothy Tickle, Matthew Brian Couger, Duygu Payzin-Dogru, Tae J Lee, Nicholas D Leigh, Tzu-Hsing Kuo, Francis G Davis, Joel Bateman, Sevara Bryant, Anna R Guzikowski, Stephanie L Tsai, Steven Coyne, William W Ye, Robert M Freeman, Leonid Peshkin, Clifford J Tabin, Aviv Regev, Brian J Haas, Jessica L Whited
Mammals have extremely limited regenerative capabilities; however, axolotls are profoundly regenerative and can replace entire limbs. The mechanisms underlying limb regeneration remain poorly understood, partly because the enormous and incompletely sequenced genomes of axolotls have hindered the study of genes facilitating regeneration. We assembled and annotated a de novo transcriptome using RNA-sequencing profiles for a broad spectrum of tissues that is estimated to have near-complete sequence information for 88% of axolotl genes...
January 17, 2017: Cell Reports
Patrick Tschopp, Clifford J Tabin
The principle of homology is central to conceptualizing the comparative aspects of morphological evolution. The distinctions between homologous or non-homologous structures have become blurred, however, as modern evolutionary developmental biology (evo-devo) has shown that novel features often result from modification of pre-existing developmental modules, rather than arising completely de novo. With this realization in mind, the term 'deep homology' was coined, in recognition of the remarkably conserved gene expression during the development of certain animal structures that would not be considered homologous by previous strict definitions...
February 5, 2017: Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences
Aysu Uygur, John Young, Tyler R Huycke, Mervenaz Koska, James Briscoe, Clifford J Tabin
Anatomical proportions are robustly maintained in individuals that vary enormously in size, both within a species and between members of related taxa. However, the mechanisms underlying scaling are still poorly understood. We have examined this phenomenon in the context of the patterning of the ventral neural tube in response to a gradient of the morphogen Sonic hedgehog (SHH) in the chick and zebra finch, two species that differ in size during the time of neural tube patterning. We find that scaling is achieved, at least in part, by altering the sensitivity of the target cells to SHH and appears to be achieved by modulating the ratio of the repressive and activating transcriptional regulators, GLI2 and GLI3...
April 18, 2016: Developmental Cell
Jessica A Lehoczky, Clifford J Tabin
The tips of the digits of some mammals, including human infants and mice, are capable of complete regeneration after injury. This process is reliant on the presence of the overlaying nail organ and is mediated by a proliferative blastema. Epithelial Wnt/β-catenin signaling has been shown to be necessary for mouse digit tip regeneration. Here, we report on Lgr5 and Lgr6 (leucine-rich repeat-containing G protein-coupled receptor 5 and 6), two important agonists of the Wnt pathway that are known to be markers of several epithelial stem cell populations...
October 27, 2015: Proceedings of the National Academy of Sciences of the United States of America
Talia Y Moore, Chris L Organ, Scott V Edwards, Andrew A Biewener, Clifford J Tabin, Farish A Jenkins, Kimberly L Cooper
Recent rapid advances in experimental biology have expanded the opportunity for interdisciplinary investigations of the evolution of form and function in non-traditional model species. However, historical divisions of philosophy and methodology between evolutionary/organismal biologists and developmental geneticists often preclude an effective merging of disciplines. In an effort to overcome these divisions, we take advantage of the extraordinary morphological diversity of the rodent superfamily Dipodoidea, including the bipedal jerboas, to experimentally study the developmental mechanisms and biomechanical performance of a remarkably divergent limb structure...
November 2, 2015: Current Biology: CB
Siew Fen Lisa Wong, Vikram Agarwal, Jennifer H Mansfield, Nicolas Denans, Matthew G Schwartz, Haydn M Prosser, Olivier Pourquié, David P Bartel, Clifford J Tabin, Edwina McGlinn
The Hox genes play a central role in patterning the embryonic anterior-to-posterior axis. An important function of Hox activity in vertebrates is the specification of different vertebral morphologies, with an additional role in axis elongation emerging. The miR-196 family of microRNAs (miRNAs) are predicted to extensively target Hox 3' UTRs, although the full extent to which miR-196 regulates Hox expression dynamics and influences mammalian development remains to be elucidated. Here we used an extensive allelic series of mouse knockouts to show that the miR-196 family of miRNAs is essential both for properly patterning vertebral identity at different axial levels and for modulating the total number of vertebrae...
September 1, 2015: Proceedings of the National Academy of Sciences of the United States of America
Yana G Kamberov, Elinor K Karlsson, Gerda L Kamberova, Daniel E Lieberman, Pardis C Sabeti, Bruce A Morgan, Clifford J Tabin
Among the unique features of humans, one of the most salient is the ability to effectively cool the body during extreme prolonged activity through the evapotranspiration of water on the skin's surface. The evolution of this novel physiological ability required a dramatic increase in the density and distribution of eccrine sweat glands relative to other mammals and a concomitant reduction of body hair cover. Elucidation of the genetic underpinnings for these adaptive changes is confounded by a lack of knowledge about how eccrine gland fate and density are specified during development...
August 11, 2015: Proceedings of the National Academy of Sciences of the United States of America
Ariel C Aspiras, Nicolas Rohner, Brian Martineau, Richard L Borowsky, Clifford J Tabin
Despite recent advances in the understanding of morphological evolution, the genetic underpinnings of behavioral and physiological evolution remain largely unknown. Here, we study the metabolic changes that evolved in independently derived populations of the Mexican cavefish, Astyanax mexicanus. A hallmark of cave environments is scarcity of food. Cavefish populations rely almost entirely on sporadic food input from outside of the caves. To survive under these conditions, cavefish have evolved a range of adaptations, including starvation resistance and binge eating when food becomes available...
August 4, 2015: Proceedings of the National Academy of Sciences of the United States of America
Amy E Shyer, Tyler R Huycke, ChangHee Lee, L Mahadevan, Clifford J Tabin
We address the mechanism by which adult intestinal stem cells (ISCs) become localized to the base of each villus during embryonic development. We find that, early in gut development, proliferating progenitors expressing ISC markers are evenly distributed throughout the epithelium, in both the chick and mouse. However, as the villi form, the putative stem cells become restricted to the base of the villi. This shift in the localization is driven by mechanically influenced reciprocal signaling between the epithelium and underlying mesenchyme...
April 23, 2015: Cell
Patrick Tschopp, Emma Sherratt, Thomas J Sanger, Anna C Groner, Ariel C Aspiras, Jimmy K Hu, Olivier Pourquié, Jérôme Gros, Clifford J Tabin
The move of vertebrates to a terrestrial lifestyle required major adaptations in their locomotory apparatus and reproductive organs. While the fin-to-limb transition has received considerable attention, little is known about the developmental and evolutionary origins of external genitalia. Similarities in gene expression have been interpreted as a potential evolutionary link between the limb and genitals; however, no underlying developmental mechanism has been identified. We re-examined this question using micro-computed tomography, lineage tracing in three amniote clades, and RNA-sequencing-based transcriptional profiling...
December 18, 2014: Nature
Kimberly L Cooper, Karen E Sears, Aysu Uygur, Jennifer Maier, Karl-Stephan Baczkowski, Margaret Brosnahan, Doug Antczak, Julian A Skidmore, Clifford J Tabin
A reduction in the number of digits has evolved many times in tetrapods, particularly in cursorial mammals that travel over deserts and plains, yet the underlying developmental mechanisms have remained elusive. Here we show that digit loss can occur both during early limb patterning and at later post-patterning stages of chondrogenesis. In the 'odd-toed' jerboa (Dipus sagitta) and horse and the 'even-toed' camel, extensive cell death sculpts the tissue around the remaining toes. In contrast, digit loss in the pig is orchestrated by earlier limb patterning mechanisms including downregulation of Ptch1 expression but no increase in cell death...
July 3, 2014: Nature
Jerome Gros, Clifford J Tabin
Vertebrate limbs first emerge as small buds at specific locations along the trunk. Although a fair amount is known about the molecular regulation of limb initiation and outgrowth, the cellular events underlying these processes have remained less clear. We show that the mesenchymal limb progenitors arise through localized epithelial-to-mesenchymal transition (EMT) of the coelomic epithelium specifically within the presumptive limb fields. This EMT is regulated at least in part by Tbx5 and Fgf10, two genes known to control limb initiation...
March 14, 2014: Science
Nicolas Rohner, Dan F Jarosz, Johanna E Kowalko, Masato Yoshizawa, William R Jeffery, Richard L Borowsky, Susan Lindquist, Clifford J Tabin
In the process of morphological evolution, the extent to which cryptic, preexisting variation provides a substrate for natural selection has been controversial. We provide evidence that heat shock protein 90 (HSP90) phenotypically masks standing eye-size variation in surface populations of the cavefish Astyanax mexicanus. This variation is exposed by HSP90 inhibition and can be selected for, ultimately yielding a reduced-eye phenotype even in the presence of full HSP90 activity. Raising surface fish under conditions found in caves taxes the HSP90 system, unmasking the same phenotypic variation as does direct inhibition of HSP90...
December 13, 2013: Science
Kathryn D Kavanagh, Oren Shoval, Benjamin B Winslow, Uri Alon, Brian P Leary, Akinori Kan, Clifford J Tabin
Evolutionary theory has long argued that the entrenched rules of development constrain the range of variations in a given form, but few empirical examples are known. Here we provide evidence for a very deeply conserved skeletal module constraining the morphology of the phalanges within a digit. We measured the sizes of phalanges within populations of two bird species and found that successive phalanges within a digit exhibit predictable relative proportions, whether those phalanges are nearly equal in size or exhibit a more striking gradient in size from large to small...
November 5, 2013: Proceedings of the National Academy of Sciences of the United States of America
Johanna E Kowalko, Nicolas Rohner, Tess A Linden, Santiago B Rompani, Wesley C Warren, Richard Borowsky, Clifford J Tabin, William R Jeffery, Masato Yoshizawa
When an organism colonizes a new environment, it needs to adapt both morphologically and behaviorally to survive and thrive. Although recent progress has been made in understanding the genetic architecture underlying morphological evolution, behavioral evolution is poorly understood. Here, we use the Mexican cavefish, Astyanax mexicanus, to study the genetic basis for convergent evolution of feeding posture. When river-dwelling surface fish became entrapped in the caves, they were confronted with dramatic changes in the availability and type of food source and in their ability to perceive it...
October 15, 2013: Proceedings of the National Academy of Sciences of the United States of America
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