Biology subjects

Adhyapok, P.

Publications and source records attributed to Adhyapok, P..

3 recordsLinked to original sources

bioRxiv2025

Tissue-wide, synchronous Erk oscillations time the segmentation of the zebrafish notochord

The generation of a segmented body plan is a hallmark of vertebrate development. Biological oscillators provide a mechanism for timing the formation of repeated structures, yet to date only a few examples of signaling oscillators have been identified in development. Here, we show that the periodic addition of mineralizing segments in the zebrafish notochord is timed by tissue-wide oscillations of Erk activity. We report delayed oscillations in the transcription of spry and dusp genes, suggesting that they act as negative feedback. Erk activity is regulated by EGFR signaling and increased egf expression marks the emergence of oscillations via an infinite-period bifurcation, revealing the mechanism controlling the onset of notochord segmentation and the tunability of the oscillator. Our results show a remarkable degree of synchronization across the notochord and reveal an instance of biological clocks timing a patterning process, crucial for the development of the vertebral column from the notochord.

developmental biology↗

bioRxiv2023

Axial segmentation by iterative mechanical signaling

In bony fishes, formation of the vertebral column, or spine, is guided by a metameric blueprint established in the epithelial sheath of the notochord. Generation of the notochord template begins days after somitogenesis and even occurs in the absence of somite segmentation. However, patterning defects in the somites lead to imprecise notochord segmentation, suggesting these processes are linked. Here, we reveal that spatial coordination between the notochord and the axial musculature is necessary to ensure segmentation of the zebrafish spine both in time and space. We find that the connective tissues that anchor the axial skeletal musculature, known as the myosepta in zebrafish, transmit spatial patterning cues necessary to initiate notochord segment formation, a critical pre-patterning step in spine morphogenesis. When an irregular pattern of muscle segments and myosepta interact with the notochord sheath, segments form non-sequentially, initiate at atypical locations, and eventually display altered morphology later in development. We determine that locations of myoseptum-notochord connections are hubs for mechanical signal transmission, which are characterized by localized sites of deformation of the extracellular matrix (ECM) layer encasing the notochord. The notochord sheath responds to the external mechanical changes by locally augmenting focal adhesion machinery to define the initiation site for segmentation. Using a coarse-grained mathematical model that captures the spatial patterns of myoseptum-notochord interactions, we find that a fixed-length scale of external cues is critical for driving sequential segment patterning in the notochord. Together, this work identifies a robust segmentation mechanism that hinges upon mechanical coupling of adjacent tissues to control patterning dynamics.

developmental biology↗

bioRxiv2019

A Mechanical Model of Early Somite Segmentation

The clock-and-wavefront model (CW) hypothesizes that the formation of somites in vertebrate embryos results from the interplay of molecular oscillations with a wave traveling along the body axis. This model however does not explain how molecular information is interpreted by cells to modulate their rearrangement into somites. Here we performed Scanning Electron Microscopy (SEM) on the pre-somitic mesoderm (PSM) of chicken embryos at stages 11-12 to describe in detail the cell shape changes occurring along the axis of the PSM. This reveals a wave of epithelialization of the dorsal PSM that precedes somite segmentation. Signs of spatially periodic apical constriction appear in this layer starting at least 3-4 somite lengths caudal to the most recently formed somite. The sizes of these clusters correspond to the typical diameter of chicken somites. We propose that a mechanical instability process leads to the separation of cells into these structures and positions the future inter-somite boundaries. We present a model in which a wave of apical constriction leads to increasing tension and periodic failure of adhesion junctions within the dorsal epithelial layer of the PSM, thus positioning somite boundaries. This model can produce spatially periodic segments whose size depends on the speed of the contraction wave (W) and the rate of increase of apical contractility ({Lambda}). The {Lambda}/W ratio determines whether this mechanism produces spatially and temporally regular or irregular segments, and whether segment sizes increase with the wave speed (scaling) as in the CW model. We discuss the limitations of a purely mechanical model of somite segmentation and the role of biomechanics along with CW during somitogenesis.

developmental biology↗