Biology subjects

Lemma, B.

Publications and source records attributed to Lemma, B..

4 recordsLinked to original sources

bioRxiv2025

Biophysical mechanisms of morphogenesis in lizard lungs

The lungs of squamate reptiles (lizards and snakes) are highly diverse, exhibiting single chambers, multiple chambers, transitional forms with two to three chambers, along with a suite of other anatomical features, including finger-like epithelial projections into the body cavity known as diverticulae. During embryonic development of the simple, sac-like lungs of anoles, the epithelium is pushed through the openings of a pulmonary smooth muscle mesh by the forces of luminal fluid pressure. This process of stress ball morphogenesis generates the faveolar epithelium typical of squamate lungs. Here, we compared embryonic lung development in brown anoles, leopard geckos, and veiled chameleons to determine if stress ball morphogenesis is conserved across squamates and to understand the physical processes that generate transitional-chambered lungs with diverticulae. We found that epithelial protrusion through the holes in a pulmonary smooth muscle mesh is conserved across squamates. Surprisingly, however, we found that luminal inflation is not conserved. Instead, leopard geckos and veiled chameleons appear to generate their faveolae via epithelial folding downstream of epithelial proliferation. We also found experimental and computational evidence suggesting that the transitional chambers and diverticulae of veiled chameleon lungs develop via apical constriction, a process known to be crucial for airway branching in the bird lung. Thus, distinct morphogenetic mechanisms generate epithelial diversity in squamate lungs, which may underpin their species-specific physiological and ecological adaptations.

developmental biology↗

bioRxiv2025

Patterns of Mitochondrial ATP Predict Tissue Folding

The construction of complex tissue shapes during embryonic development results from spatial patterns of gene expression and mechanical forces fueled by chemical energy from ATP hydrolysis. We find that chemical energy is similarly patterned during morphogenesis. Specifically, mitochondria are locally enriched at the apical sides of epithelial cells during apical constriction, which is widely used across the animal kingdom to fold epithelial tissues. Timelapse imaging, spatial transcriptomics, and measurements of oxygen consumption rate reveal that mitochondrial density, potential, and ATP increase in epithelial cells prior to actomyosin contraction and tissue folding, which is prevented by inhibiting oxidative phosphorylation. Mitochondrial enrichment and apicobasal patterning are conserved during apical constriction in flies, chicks, and mice, and these subcellular patterns can be used to predict computationally patterns of tissue folding. These findings highlight a spatial dimension of bioenergetics in embryonic development.

developmental biology↗

bioRxiv2022

Origins of smooth muscle and evolutionary specializations of the pulmonary mesenchyme in the vertebrate lung

Lungs exhibit strikingly diverse epithelial architectures - from the branched airways of mammals to the sac-like lungs of lizards and the looped airways of birds. Across lineages, the pulmonary mesenchyme gives rise to smooth muscle that interacts with and shapes the underlying pulmonary epithelium. In mammals and lizards, pulmonary smooth muscle forms early and drives epithelial branching, whereas in birds it appears only after morphogenesis is largely complete. The developmental basis for this delay has remained unclear. Using comparative single-cell RNA sequencing, ATAC-sequencing, and imaging of mouse, anole, and chicken embryos, we found that smooth muscle in the chicken lung is transcriptionally similar to vascular, rather than visceral, smooth muscle. Strikingly, imaging revealed smooth muscle cells extending between the pulmonary vasculature and the epithelium, and surgical removal of these vessels prevented the formation of smooth muscle around the airways. The vascular transcription factor PITX2 was highly expressed in these cells and its knockdown markedly reduced smooth muscle differentiation. Taken together, these findings identify vascular smooth muscle as the developmental source of pulmonary smooth muscle in birds and establish PITX2 as a key regulator of this lineage transition, revealing an unexpected developmental and evolutionary link between the circulatory and respiratory systems.

developmental biology↗

bioRxiv2022

Plasticity in airway smooth muscle differentiation during mouse lung development

Smooth muscle differentiation has been proposed to sculpt airway epithelial branches in mammalian lungs. Serum response factor (SRF) acts with its cofactor myocardin to promote the expression of contractile smooth muscle markers. However, smooth muscle cells exhibit a variety of phenotypes beyond contractile that are independent of SRF/myocardin-induced transcription. To determine whether airway smooth muscle exhibits phenotypic plasticity during embryonic development, we deleted Srf from the pulmonary mesenchyme. Srf-mutant lungs branch normally, and the mesenchyme exhibits normal cytoskeletal features and patterning. scRNA-seq revealed an Srf-null smooth muscle cluster wrapping the airways of mutant lungs that lacks contractile smooth muscle markers but retains many features of control smooth muscle. Srf-null airway smooth muscle exhibits a synthetic phenotype, compared to the contractile phenotype of mature wildtype airway smooth muscle. Our findings reveal plasticity in airway smooth muscle differentiation and demonstrate that a synthetic smooth muscle layer is sufficient for airway branching morphogenesis.

developmental biology↗