Biology subjects

McLaren, S. B. P.

Publications and source records attributed to McLaren, S. B. P..

4 recordsLinked to original sources

bioRxiv2024

TiFM2.0 - Versatile mechanical measurement and actuation in live embryos

During development, spatial-temporally patterned tissue-level stresses and mechanical properties create diverse tissue shapes. To understand the mechanics of small-scale embryonic tissues, precisely controlled sensors and actuators are needed. Previously, we reported a control-based approach named tissue force microscopy (TiFM1.0), which combines dynamic positioning and imaging of an inserted cantilever probe to directly measure and impose forces in early avian embryos. Here we present an upgraded system (TiFM2.0) that utilises interferometer positioning to minimise probe holder footprint, enhancing accessibility and imaging signal. This new design enables a double-probe configuration for bidirectional stretching, compression and stress propagation experiments. As proof-of-concept, we showcase a variety of examples of TiFM2.0 applications in chicken and zebrafish embryos, including the characterization of mechanical heterogeneities important for the morphogenesis of the chicken posterior body axis. We also present simplified designs and protocols for the replication of TiFM systems with minimal custom engineering for developmental biology labs.

developmental biology↗

bioRxiv2024

Differential tissue deformability underlies shape divergence of the embryonic brain and spinal cord under fluid pressure

An expanded brain enables the complex behaviours of vertebrates that promote their adaptation in diverse ecological niches1-3. Initial morphological differences between the brain and spinal cord emerge as the antero-posteriorly patterned neural plate folds to form the neural tube4-7 during embryonic development. Following neural tube closure, a dramatic expansion of the brain diverges its shape from the spinal cord8, setting their distinct morphologies for further development9,10. How the brain and the spinal cord expand differentially remains unclear. Here, using the chicken embryo as a model, we show that the hindbrain expands through dorsal tissue thinning under a positive hydrostatic pressure from the neural tube lumen11,12 while the dorsal spinal cord shape resists the same pressure. Using magnetic droplets and atomic force microscopy, we reveal that the dorsal tissue in the hindbrain is more fluid than in the spinal cord. The dorsal hindbrain harbours more migratory neural crest cells13 and exhibits reduced apical actin and a disorganised laminin matrix compared to the dorsal spinal cord. Blocking the activity of neural crest-associated matrix metalloproteinases inhibited dorsal tissue thinning, leading to abnormal brain morphology. Transplanting early dorsal hindbrain cells to the spinal cord was sufficient to create a region with expanded brain-like morphology including a thinned-out roof. Our findings open new questions in vertebrate head evolution and neural tube defects, and suggest a general role of mechanical pre-pattern in creating shape differences in epithelial tubes.

developmental biology↗

bioRxiv2023

Lumen pressure modulation in chicken embryos

Pressure exerted by fluid contained within a lumen plays a crucial role in the growth, morphogenesis and patterning of epithelial organs. Accurate modulation of lumen pressure in the developing embryo requires sensitive and robust methods that can detect and vary pressure in the range of tens to hundreds of Pascals (Pa). Here we describe a simple, cost- effective method for setting up a pressure modulation apparatus combining a high-sensitivity pressure sensor and a water column whose height can be finely tuned. We demonstrate lumen pressure control using the developing brain of early chicken embryos.

developmental biology↗

bioRxiv2021

Anterior expansion and posterior addition to the notochord mechanically coordinate embryo axis elongation

During development the embryo body progressively elongates from head-to-tail along the anterior-posterior (AP) axis. Multiple tissues contribute to this elongation through a combination of convergence and extension and/or volumetric growth. How force generated by the morphogenesis of one tissue impacts the morphogenesis of other axial tissues to achieve an elongated axis is not well understood. The notochord, a rod-shaped tissue possessed by all vertebrates, runs across the entire length of the somitic compartment and is flanked on either side by the developing somites in the segmented region of the axis and presomitic mesoderm in the posterior. Cells in the notochord undergo an expansion that is constrained by a stiff sheath of extracellular matrix, that increases the internal pressure in the notochord allowing it to straighten and elongate. Therefore, it is appropriately positioned to play a role in mechanically elongating the somitic compartment. Here, we use multi-photon mediated cell ablation to remove specific regions of the developing notochord and quantify the impact on axis elongation. We show that anterior notochord cell expansion generates a force that displaces notochord cells posteriorly relative to adjacent axial tissues and contributes to the elongation of segmented tissue during post-tailbud stages of development. Crucially, unexpanded cells derived from progenitors at the posterior end of the notochord provide resistance to anterior notochord cell expansion, allowing for force generation across the AP axis. Therefore, notochord cell expansion beginning in the anterior, and addition of cells to the posterior notochord, act as temporally coordinated morphogenetic events that shape the zebrafish embryo AP axis.

developmental biology↗