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Tabin, C.

Publications and source records attributed to Tabin, C..

6 recordsLinked to original sources

Human foregut morphogenesis exhibits murine-like molecular patterning but avian-like epithelial architecture

Animal models are indispensable for understanding human development, yet evolutionary relatedness does not ensure developmental similarity at all biological scales. In tracheal-esophageal separation (TES), which splits the embryonic foregut into respiratory and digestive tubes in all tetrapods, genetic mouse models rarely reproduce the predominant human malformation, esophageal atresia with tracheoesophageal fistula (EA/TEF). By comparing human, mouse, and chick foreguts, we uncover a mosaic pattern of developmental conservation. The human foregut resembles the mouse in its molecular patterning, but more closely resembles the chick in its densely pseudostratified epithelial architecture and the greater number of cells comprising the epithelial septum. Live imaging shows that epithelial pseudostratification, which depends on actomyosin contractility, is associated with slower septum resolution. Cross-species single-cell transcriptomics analysis reveals lower expression of a myosin regulatory light chain and N-cadherin, and higher expression of a myosin phosphatase subunit in the mouse foregut epithelium than in the human and chick, suggesting candidate molecular mechanisms of these morphological differences. Induction of ectopic BMP signaling through in vivo electroporation in chick embryos recapitulated an EA/TEF-like malformation. These findings suggest that human foregut morphogenesis combines murine-like patterning and avian-like epithelial organization. The chick embryo thus represents an important complementary model for investigating epithelial mechanisms underlying human foregut malformations.

cell biology↗

Courtship vocalizations in male ducks: spectral composition and resonance of the syringeal bulla

Ducks display a unique and dramatic sexual dimorphism in their vocal organ, the syrinx. Males have a left-sided bulla that is not present in females and that has been long hypothesized to play a role in courtship vocalizations, though this connection has never been tested. The large, hollow morphology of the bulla and its proximity to the sound-producing vocal folds introduce the possibility that it may work as a Helmholtz resonator, which makes it possible to predict the resonance frequencies enhanced by this structure. We find that during early ontogeny, the distribution of energy across the harmonic spectrum of contact calls is not different between males and females. We then used micro-CT scans of duck syrinxes to estimate resonance frequencies of the bullae and compared these to spectral features of their vocalizations. This comparison overall supports the idea that the bulla resonance may specifically enhance aspects of courtship vocalizations, especially in species that have a tonal courtship whistle. We also see potential influence in non-courtship vocalizations, which could be explored further with a greater understanding of the input of other vocal tract features that influence vocalization. We observed that bulla size is positively correlated with bird body mass with the largest exception in the Common Eider, which had a small bulla for its body mass and for which we saw no evidence of bulla-input to its vocalizations. This study found support for the long-held hypothesis that the adult male duck bulla influences resonance frequencies, in particular in courtship vocalizations.

physiology↗

Direct Reprogramming of Non-limb Fibroblasts toCells with Properties of Limb Progenitors

The early limb bud consists of mesenchymal progenitors (limb progenitors) derived from the lateral plate mesoderm (LPM) that produce most of the tissues of the mature limb bud. The LPM also gives rise to the mesodermal components of the trunk, flank and neck. However, the mesenchymal cells generated at these other axial levels cannot produce the variety of cell types found in the limb bud, nor can they be directed to form a patterned appendage-like structure, even when placed in the context of the signals responsible for organizing the limb bud. Here, by taking advantage of a direct reprogramming approach, we find a set of factors (Prdm16, Zbtb16, and Lin28) normally expressed in the early limb bud, that are capable of imparting limb progenitor-like properties to non-limb fibroblasts. Cells reprogrammed by these factors show similar gene expression profiles, and can differentiate into similar cell types, as endogenous limb progenitors. The further addition of Lin41 potentiates proliferation of the reprogrammed cells while suppressing differentiation. These results suggest that these same four key factors may play pivotal roles in the specification of endogenous limb progenitors.

developmental biology↗

Evolution of the gastrointestinal tract morphology and plasticity in cave-adapted Mexican tetra, Astyanax mexicanus

The gastrointestinal tract has evolved in numerous ways to allow animals to optimally assimilate energy from different foods. The morphology and physiology of the gut is plastic and can be greatly altered by diet in some animals. In this study, we investigated the evolution and plasticity of gastrointestinal tract morphology by comparing laboratory-raised cave- and river-adapted forms of the Mexican tetra, Astyanax mexicanus, reared under different dietary conditions. In the wild, river-dwelling populations (surface fish) consume plants and insects throughout the year, while cave-dwelling populations (cavefish) live in a perpetually dark environment and depend on nutrient-poor food brought in by bats or seasonal floods. We found that multiple cave populations converged on a reduced number of digestive appendages called pyloric caeca and that some cave populations have a lengthened gut while others have a shortened gut. Moreover, we identified differences in how gut morphology and proliferation respond to diet between surface fish and cavefish. Using a combination of quantitative genetic mapping, population genetics, and RNA sequencing, we found that changes to the molecular and genetic pathways that influence cell proliferation, differentiation, and immune system function may underlie evolution of the cavefish gut.

evolutionary biology↗

Genetic architecture underlying changes in carotenoid accumulation during the evolution of the Blind Mexican cavefish, Astyanax mexicanus

Carotenoids are yellow to orange pigments produced by plants, bacteria, and fungi. They are consumed by animals and metabolized to produce molecules essential for gene regulation, vision, and pigmentation. Cave animals represent an interesting opportunity to understand how carotenoid utilization evolves. Caves are devoid of light, eliminating primary production of energy through photosynthesis and therefore limiting carotenoid availability. Moreover, the selective pressures that favor carotenoid-based traits, like pigmentation and vision, are relaxed. Astyanax mexicanus is a species of fish with river-adapted (surface) and multiple cave-adapted populations (i.e. Tinaja, Pachon, Molino). Cavefish exhibit regressive features such as loss of eyes and melanin pigment, and constructive traits, like increased sensory neuromasts and starvation resistance. Here we show that unlike surface fish, Tinaja and Pachon cavefish accumulate carotenoids in the visceral adipose tissue (VAT). Carotenoid accumulation is not observed in Molino cavefish indicating that it is not an obligatory consequence of eye loss. We used quantitative trait loci mapping and RNA sequencing to investigate genetic changes associated with this trait. Our findings suggest that multiple stages of carotenoid processing may be altered in cavefish, including absorption and transport of lipids, cleavage of carotenoids into un-pigmented molecules, and differential development of intestinal cell types involved in carotenoid assimilation. Our study establishes A. mexicanus as a model to study the genetic basis of natural variation in carotenoid accumulation and how it impacts physiology.\n\nResearch HighlightsO_LICavefish accumulate carotenoids in the visceral adipose tissue (VAT)\nC_LIO_LIGenetic mapping reveals candidate genes associated with yellow VAT\nC_LIO_LICarotenoid accumulation is linked with decreased expression of carotenoid-processing genes\nC_LI

evolutionary biology↗

In situ measurement of absolute concentrations by Normalized Raman Imaging

Cell mass and its chemical composition are important aggregate cellular variables for physiological processes including growth control and tissue homeostasis. Despite their central importance, it has been difficult to quantitatively measure these quantities from single cells in intact tissue. Here, we introduce Normalized Raman Imaging (NoRI), a Stimulated Raman Scattering (SRS) microscopy method that provides the local concentrations of protein, lipid and water from live or fixed tissue samples with high spatial resolution. Using NoRI, we demonstrate that single cell protein, lipid and water concentrations are maintained in a tight range in cells under same physiological conditions and are altered in different physiological states such as cell cycle stages, attachment to substrates of different stiffness, or by entering senescence. In animal tissues, protein and lipid concentration varies with cell types, yet an unexpected cell-to-cell heterogeneity was found in cerebellar Purkinje cells. Protein and lipid concentration profile provides a new means to quantitatively compare disease-related pathology as demonstrated using models of Alzheimers disease. Our demonstration shows that NoRI is a broadly applicable tool for probing the biological regulation of protein mass, lipid mass and water in cellular and tissue growth, homeostasis, and disease.

bioengineering↗