Biology subjects

Anthwal, N.

Publications and source records attributed to Anthwal, N..

6 recordsLinked to original sources

bioRxiv2026

The gut microbiome of infants with hypoplastic left heart syndrome is enriched in pathobionts and exhibits altered responses to nutritional intervention

Congenital heart disease (CHD) can expose infants to chronic cyanosis, altered intestinal perfusion, and prolonged hospitalization. Altered gut microbiota has been linked to inflammation and gut barrier dysfunction in CHD cohorts, but few studies have examined whether cardiac severity and oxygenation shape microbial function, or whether this can be leveraged nutritionally, particularly for hypoplastic left heart syndrome (HLHS), the most hemodynamically severe common CHD lesion. We performed shotgun metagenomics on stool from 28 infants spanning the CHD severity spectrum, including HLHS (n=7), ventricular septal defect (n=8), tetralogy of Fallot (n=9), atrioventricular septal defect (n=2), and other lesions (n=2). We reconstructed 609 metagenome-assembled genomes, used for taxonomic and functional profiling, differential abundance testing, and oxygenation-associated modeling. Cardiac disease group was the strongest driver of taxonomic composition, with enrichment of the opportunistic Klebsiella specific to HLHS over contributions of feeding modality, birth type, or baseline oxygen saturation alone. HLHS communities showed a dual functional signature: depletion of core biosynthetic pathways, including aminoacyl-tRNA and peptidoglycan biosynthesis, alongside expansion of Enterobacteriaceae-driven aromatic amino acid catabolism and ABC transporters; this dual signature varied continuously with oxygenation. We then built infant-specific community metabolic models curated for human milk oligosaccharide metabolism and simulated a panel of feeding regimens. Individual microbiome identity, rather than diet, was the dominant determinant of predicted short-chain fatty acid (SCFA) production. In silico screening of dietary supplements identified threonine, methionine, and mucin-derived sugars as the strongest candidates for enhancing SCFA output, concentrated largely in formula-fed communities. These findings describe a coordinated shift in gut microbial function linked to CHD types and oxygenation, and provide a hypothesis-generating framework for microbiome-informed nutritional interventions in infants with severe CHD.

bioinformatics↗

bioRxiv2024

FSP1 stem/progenitor cells are essential for TMJ growth and homeostasis

The temporomandibular joint (TMJ) is one of the most used joints in the body. Defects and wear in the cartilage of the joint, condyle, and fibrocartilage disc lie at the heart of many common TMJ disorders. During postnatal development the condyle acts as a growth centre for the mandible with cells moving as a conveyor belt away from the top of the condyle as they differentiate. The superficial layers of the condyle have been proposed to contain stem/progenitor populations to allow growth and maintain homeostasis. Here we have focused on the role of FSP1 (also known as S100a4), as a key fibroblast stem/progenitor marker for the condyle. Lineage tracing using FSP1-Cre;mTmG mice revealed that FSP1-positive cells were restricted to the superficial fibroblast zone giving rise to all layers of the condyle over time. The FSP1-expressing cells overlapped with other putative stem cell markers of the condyle, Gli1 and Scleraxis. BrdU pulse chase experiments highlighted that a subset of FSP1 fibrocartilage were label-retaining, suggesting that FSP1 labels a novel stem/progenitor cell population in the condyle. Destruction of FSP1-expressing cells by conditional diphtheria toxin activity in FSP1-Cre;DTA mice resulted in severe TMJ osteoarthritis (TMJOA) with loss of the cartilage structure. Lgr5 expressing cells in the superficial layer of the condyle, have previously been shown to create a Wnt inhibitory niche. FSP1 expression postnatally was associated with a reduction in canonical Wnt activity in the condyle. Importantly, constitutive activation of Wnt/{beta} catenin in FSP1 cells, led to a downregulation of FSP1 and progressive postnatal loss of TMJ condylar hyaline cartilage due to loss of the superficial stem/progenitor cells. These data demonstrate a novel role for FSP1-expressing cells in the superficial zone in growth and maintenance of the TMJ condylar cartilage and highlight the importance of regulating Wnt activity in this population.

developmental biology↗

bioRxiv2021

Growth rate as a modulator of tooth patterning during adaptive radiations

Tooth classes are a mammalian innovation that has contributed to the evolutionary success of mammals. However, our understanding of how tooth classes have evolved and diversified remains limited. Here, we use the evolutionary radiation of noctilionoid bats, the most diverse clade of mammals in terms of diet type, as a model system to show how the tooth developmental program evolved during the adaptation to new diet types. We combined morphological, developmental, cellular, and modeling approaches, to investigate the developmental differences between two tooth classes, molars and premolars and the mechanisms driving their diversification. We demonstrate that tooth classes develop through independent developmental cascades that deviate from classical models. Then we showed that the dramatic diversification of tooth number and size is driven by the modulation of the growth rate of the jaw, explaining the rapid gain/loss of teeth during the evolution of this clade. Finally, we propose a mathematical model that recapitulates the successive appearance of tooth buds and supports the hypothesis that growth acts as a key driver of the evolution of tooth number and size by tinkering with reaction/diffusion processes. Our results demonstrate developmental independence between mammalian tooth classes and provide a mechanism to explain their rapid diversification. More broadly, these results reveal how simple modifications of one developmental mechanism by another can drive the evolution of repeated structures during adaptive radiations.

evolutionary biology↗

bioRxiv2021

Getting out of a mammalian egg: the egg tooth and caruncle of the echidna

In the short-beaked echidna, Tachyglossus aculeatus, after an initial period of in utero development, the egg is laid in the pouch and incubated for 10 days. During this time, the fetuses develop an egg tooth and caruncle to help them hatch. However, there are only a few historical references that describe the development of the monotreme egg tooth. Using unprecedented access to echidna pre- and post-hatching tissues, the egg tooth and caruncle were assessed by micro-CT, histology and immunofluorescence, to map the changes at the morphological and molecular level. Unlike mammalian tooth germs that develop by invagination of a placode, the echidna egg tooth developed by evagination, similar to that of the first teeth in some reptiles. The egg tooth ankylosed to the premaxilla, rather than forming a mammalian thecodont attachment, with loss of the egg tooth post-hatching associated with high levels of odontoclasts, and apoptosis. The caruncle formed as a separate mineralisation from the adjacent nasal capsule, and as observed in birds and turtles, the nasal region epithelium expressed markers of cornification. Together, this highlights that the monotreme egg tooth shares many similarities with reptilian teeth, suggesting that this tooth is conserved from a common ancestor of mammals and reptiles.

evolutionary biology↗

bioRxiv2020

A cranio-incudo joint as the solution to early birth in marsupials and monotremes

Mammals articulate their jaws using a novel joint between the dentary and squamosal bones. In eutherian mammals, this joint forms in the embryo, supporting feeding and vocalisation from birth. In contrast, marsupials and monotremes exhibit extreme altriciality and are born before the bones of the novel mammalian jaw joint form. These mammals need to rely on other mechanisms to allow them to feed. Here we show that this vital function is carried out by the earlier developing, cartilaginous incus of the middle ear, abutting the cranial base to form a cranio-mandibular articulation. The nature of this articulation varies between monotremes and marsupials, with monotremes retaining a double articulation, similar to that described in the fossil mammaliaform, Morganucodon, while marsupials use a versican rich matrix to stabilise the jaw against the cranial base. These findings provide novel insight into the evolution of mammals and the relationship between the jaw and ear.

developmental biology↗

bioRxiv2020

The TMJ disc is a common ancestral feature in all mammals, as evidenced by the presence of a rudimentary disc during monotreme development.

The novel mammalian jaw joint, known in humans as the temporomandibular joint or TMJ, is cushioned by a fibrocartilage disc. This disc is secondarily absent in therian mammals that have lost their dentition, such as giant anteaters and some baleen whales. The disc is also absent in all monotremes. However, it is not known if the absence in monotremes is secondary to the loss of dentition, or if it is an ancestral absence. We use museum held platypus and echidna histological sections to demonstrate that the developing monotreme jaw joint forms a disc primordium that fails to mature and become separated from the mandibular condyle. We then show that monotreme developmental anatomy is similar to that observed in transgenic mouse mutants with reduced musculature. We therefore suggest that the absence of the disc on monotremes is a consequence of the changes in jaw musculature associated with the loss of adult teeth. Taken together, these data indicate that the ancestors of extant monotremes likely had a jaw joint disc, and that the disc evolved in the last common ancestor or all mammals.

developmental biology↗