Clifford J. Tabin

All living tetrapods have a one-to-two branching pattern in the embryonic proximal limb skeleton, with a single element at the base of the limb (the humerus or femur) that articulates distally with two parallel radials (the ulna and radius or the tibia and fibula). This pattern is also seen in the fossilized remains of stem-tetrapods, including the fishlike members of the group, in which despite the absence of digits, the proximal parts of the fin skeleton clearly resemble those of later tetrapods. However, little is known about the developmental mechanisms that establish and canalize this highly conserved pattern...

In its most basic conception, a novelty is simply something new. However, when many previously proposed evolutionary novelties have been illuminated by genetic, developmental, and fossil data, they have refined and narrowed our concept of biological "newness." For example, they show that these novelties can occur at one or multiple levels of biological organization. Here, we review the identity of structures in the avian vocal organ, the syrinx, and bring together developmental data on airway patterning, structural data from across tetrapods, and mathematical modeling to assess what is novel...

Through the course of evolution, the gastrointestinal (GI) tract has been modified to maximize nutrient absorption, forming specialized segments that are morphologically and functionally distinct. Here we show that the GI tract of the Mexican tetra, Astyanax mexicanus, has distinct regions, exhibiting differences in morphology, motility, and absorption. We found that A. mexicanus populations adapted for life in subterranean caves exhibit differences in the GI segments compared to those adapted to surface rivers...

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Little is known about the genetic basis of behavioral choice, such as temperature preference, especially in natural populations. Thermal preference can play a key role in habitat selection, for example in aquatic species. Examining this behavior on a genetic level requires access to individuals or populations of the same species that display distinct temperature preferences. Caves provide a uniquely advantageous setting to tackle this problem, as animals colonizing caves encounter an environment that generally has a different, and far more stable, annual temperature than what is encountered on the outside...

The gastrointestinal tract is an essential system of organs required for nutrient absorption. As a simple tube early in development, the primitive gut is patterned along its anterior-posterior axis into discrete compartments with unique morphologies relevant to their functions in the digestive process. These morphologies are acquired gradually through development as the gut is patterned by tissue interactions, both molecular and mechanical in nature, involving all three germ layers. With a focus on midgut morphogenesis, we review work in the chick embryo demonstrating how these molecular signals and mechanical forces sculpt the developing gut tube into its mature form...

Periodic food shortages are a major challenge faced by organisms in natural habitats. Cave-dwelling animals must withstand long periods of nutrient deprivation, as-in the absence of photosynthesis-caves depend on external energy sources such as seasonal floods. Here we show that cave-adapted populations of the Mexican tetra, Astyanax mexicanus, have dysregulated blood glucose homeostasis and are insulin-resistant compared to river-adapted populations. We found that multiple cave populations carry a mutation in the insulin receptor that leads to decreased insulin binding in vitro and contributes to hyperglycaemia...

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...

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...

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...

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...

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...

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...

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...

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...

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...

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...

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...

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...

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...