Biology subjects

Prakash, V. N.

Publications and source records attributed to Prakash, V. N..

3 recordsLinked to original sources

bioRxiv2024

PFAS Compounds PFOA and Gen X are Teratogenic to Sea Urchin Embryos

Per-and polyfluorinated substances (PFAS) are synthetic chemicals that are used to make fluoropolymer coatings found in many products, such as non-stick pans, clothing, cosmetics, and food packaging. These highly persistent molecules are known as "forever chemicals" since they neither degrade environmentally nor break down enzymatically within biological systems. PFAS compounds readily contaminate water sources, and as a result, certain PFAS molecules have bioaccumulated in exposed species including humans. The purpose of this study was to define the effect of two PFAS molecules, the ostensibly more toxic perfluorooctanoic acid (PFOA) and the more recent, reportedly safer chemical hexafluoropropylene oxide dimer acid (Gen X), on the development of Lytechinus variegatus sea urchin embryos. We examined the effects of PFOA and Gen X on development and patterning using morphological analysis, immunostaining, HCR-FISH, and Particle Image Velocimetry (PIV). The results show that both PFAS compounds are teratogenic to sea urchin embryos. PFOA and Gen X each function at different intervals during development and provoke distinct phenotypic and gene expression outcomes. Despite beliefs that Gen X would be a safer alternative, our findings indicate that Gen X has earlier and more severe effects on endomesoderm and dorsal-ventral axis specification, neural development and function, and pattern formation compared to PFOA. These results illustrate the dangerous teratogenic potential of environmentally accumulating PFAS like Gen X, underscoring the negative ecological implications that accompany continuing commercial and industrial use of PFAS in the absence of remediation strategies. HIGHLIGHTSO_LIGen X is more teratogenic in sea urchins than PFOA C_LIO_LIGen X acts earlier than PFOA and perturbs axial and germ layer specification C_LIO_LIEach PFAS reduces neural numbers and perturbs ciliary behavior and swimming C_LI

developmental biology↗

bioRxiv2024

Cellular flows initiate left-right patterning prior to laterality gene expression in amniotes

A bilateral body plan is predominant throughout the animal kingdom. Bilaterality of amniote embryos becomes recognizable as midline morphogenesis begins at gastrulation, bisecting an embryonic field into the left and right sides, and left-right asymmetry patterning follows. While a series of laterality genes expressed after the left-right compartmentalization has been extensively studied, the laterality patterning prior to and at the initiation of midline morphogenesis has remained unclear. Here, through a biophysical quantification in a high spatial and temporal resolution, applied to a chick model system, we show that a large-scale bilateral counter-rotating cellular flow, termed as polonaise movements, display left-right asymmetries in early gastrulation. This cell movement starts prior to the formation of the primitive streak (the earliest midline structure) and the subsequent appearance of Hensens node (the left-right organizer). The cellular flow speed and vorticity unravel the location and timing of the left-right asymmetries. The bilateral flows displayed a Right dominance after six hours since the start of cell movements. Mitotic arrest that diminishes primitive streak formation resulted in changes in the bilateral flow pattern, but the Right dominance persisted. Our data indicate that the left-right asymmetry in amniote gastrula becomes detectable earlier than suggested by current models, which assume that the asymmetric regulation of the laterality signals at the node leads to the left-right patterning. More broadly, our results suggest that physical processes can play an unexpected but significant role in influencing left-right laterality during embryonic development. Significance StatementBilaterians are defined by a bilaterally symmetrical body plan. Vertebrates exhibit external bilateral symmetry but display left-right (LR) asymmetry in their internal organs. Amniote embryos switch the patterning of internal organs from bilateral symmetry to LR-asymmetry. Using chick embryos as a model system, here we examined the initiation of LR symmetry breaking. Our biophysical approaches to quantify cellular flows inferred that LR symmetry breaking occurs before the formation of Hensens node, a LR organizer, which serves as a signaling center for LR patterning-gene programs. Our work demonstrates that quantitative biophysical parameters can help unravel the initiation of LR symmetry breaking, suggesting an involvement of physical mechanisms in this critical biological patterning process.

biophysics↗

bioRxiv2023

Coupling and uncoupling of midline morphogenesis and cell flow in amniote gastrulation

Large-scale cell flow characterizes gastrulation in animal development. In amniote gastrulation, particularly in avian gastrula, a bilateral vortex-like counter-rotating cell flow, called polonaise movements, appears along the midline. Here, through experimental manipulations, we addressed relationships between the polonaise movements and morphogenesis of the primitive streak, the earliest midline structure in amniotes. Suppression of the Wnt/planar cell polarity (PCP) signaling pathway maintains the polonaise movements along a deformed primitive streak. Mitotic arrest leads to diminished extension and development of the primitive streak and maintains the early phase of the polonaise movements. Ectopically induced Vg1, an axis-inducing morphogen, generates the polonaise movements, aligned to the induced midline, but disturbs the stereotypical cell flow pattern at the authentic midline. Despite the altered cell flow, induction and extension of the primitive streak are preserved along both authentic and induced midlines. Finally, we show that ectopic axis-inducing morphogen, Vg1, is capable of initiating the polonaise movements without concomitant PS extension under mitotic arrest conditions. These results are consistent with a model wherein primitive streak morphogenesis is required for the maintenance of the polonaise movements, but the polonaise movements are not necessarily responsible for primitive streak morphogenesis. Our data describe a previously undefined relationship between the large-scale cell flow and midline morphogenesis in gastrulation.

developmental biology↗