Abstract:To ensure the formation of a properly patterned embryo, multiple processes must operate harmoniously at sequential phases of development. This is implemented by mutual interactions between cells and tissues that together regulate the segregation and specification of cells, their growth and morphogenesis. The formation of the spinal cord and paraxial mesoderm derivatives exquisitely illustrate these processes. Following early gastrulation, while the vertebrate body elongates, a population of bipotent neuromesod… Show more
“…2 that additionally identify the DM, were normally expressed in treated compared to control sides or to control GFP-treated embryos ( Figure 1 A–H) [ 44 , 45 , 46 , 47 , 48 ]. However, the treated sclerotomes exhibited a notable reduction in size ( Figure 1 A–I), along with a decrease in the adjacent DMs ( Figure 1 F,H), consistent with previous findings [ 18 , 49 ].…”
Section: Resultssupporting
confidence: 91%
“…A day later, the sclerotomal markers PAX1, PAX9, as well as Meox2 and Nkx3.2 that additionally identify the DM, were normally expressed in treated compared to control sides or to control GFP-treated embryos (Figure 1A-H) [44][45][46][47][48]. However, the treated sclerotomes exhibited a notable reduction in size (Figure 1A-I), along with a decrease in the adjacent DMs (Figure 1F,H), consistent with previous findings [18,49]. Notably, staining for apoptotic cells via caspase revealed increased cell death within the Hhip-treated segments (Figure 1J,K).…”
Section: Decreasing Levels Of Shh Activity In Sclerotome By Hhip1 Enh...supporting
Derived from axial structures, Sonic Hedgehog (Shh) is secreted into the paraxial mesoderm, where it plays crucial roles in sclerotome induction and myotome differentiation. Through conditional loss-of-function in quail embryos, we investigate the timing and impact of Shh activity during early formation of sclerotome-derived vertebrae and ribs, and of lateral mesoderm-derived sternum. To this end, Hedgehog interacting protein (Hhip) was electroporated at various times between days 2 and 5. While the vertebral body and rib primordium showed consistent size reduction, rib expansion into the somatopleura remained unaffected, and the sternal bud developed normally. Additionally, we compared these effects with those of locally inhibiting BMP activity. Transfection of Noggin in the lateral mesoderm hindered sternal bud formation. Unlike Hhip, BMP inhibition via Noggin or Smad6 induced myogenic differentiation of the lateral dermomyotome lip, while impeding the growth of the myotome/rib complex into the somatic mesoderm, thus affirming the role of the lateral dermomyotome epithelium in rib guidance. Overall, these findings underscore the continuous requirement for opposing gradients of Shh and BMP activity in the morphogenesis of proximal and distal flank skeletal structures, respectively. Future research should address the implications of these early interactions to the later morphogenesis and function of the musculo-skeletal system and of possible associated malformations.
“…2 that additionally identify the DM, were normally expressed in treated compared to control sides or to control GFP-treated embryos ( Figure 1 A–H) [ 44 , 45 , 46 , 47 , 48 ]. However, the treated sclerotomes exhibited a notable reduction in size ( Figure 1 A–I), along with a decrease in the adjacent DMs ( Figure 1 F,H), consistent with previous findings [ 18 , 49 ].…”
Section: Resultssupporting
confidence: 91%
“…A day later, the sclerotomal markers PAX1, PAX9, as well as Meox2 and Nkx3.2 that additionally identify the DM, were normally expressed in treated compared to control sides or to control GFP-treated embryos (Figure 1A-H) [44][45][46][47][48]. However, the treated sclerotomes exhibited a notable reduction in size (Figure 1A-I), along with a decrease in the adjacent DMs (Figure 1F,H), consistent with previous findings [18,49]. Notably, staining for apoptotic cells via caspase revealed increased cell death within the Hhip-treated segments (Figure 1J,K).…”
Section: Decreasing Levels Of Shh Activity In Sclerotome By Hhip1 Enh...supporting
Derived from axial structures, Sonic Hedgehog (Shh) is secreted into the paraxial mesoderm, where it plays crucial roles in sclerotome induction and myotome differentiation. Through conditional loss-of-function in quail embryos, we investigate the timing and impact of Shh activity during early formation of sclerotome-derived vertebrae and ribs, and of lateral mesoderm-derived sternum. To this end, Hedgehog interacting protein (Hhip) was electroporated at various times between days 2 and 5. While the vertebral body and rib primordium showed consistent size reduction, rib expansion into the somatopleura remained unaffected, and the sternal bud developed normally. Additionally, we compared these effects with those of locally inhibiting BMP activity. Transfection of Noggin in the lateral mesoderm hindered sternal bud formation. Unlike Hhip, BMP inhibition via Noggin or Smad6 induced myogenic differentiation of the lateral dermomyotome lip, while impeding the growth of the myotome/rib complex into the somatic mesoderm, thus affirming the role of the lateral dermomyotome epithelium in rib guidance. Overall, these findings underscore the continuous requirement for opposing gradients of Shh and BMP activity in the morphogenesis of proximal and distal flank skeletal structures, respectively. Future research should address the implications of these early interactions to the later morphogenesis and function of the musculo-skeletal system and of possible associated malformations.
“…Neuro-mesodermal interactions were discussed to trigger NCC induction and delamination in the embryo. Moreover, the mesenchymal part provides guidance for migrating NCCs and growing peripheral axons ( Kahane and Kalcheim, 2021 ). Figure 1 Generation and initial characterization of neuro-mesodermal assembloids (A) Schematic representation of the experimental workflow.…”
“…Neuro-mesodermal interactions were discussed to trigger neural crest cell induction and delamination in the embryo. Moreover, the mesenchymal part provides guidance for migrating NCCs and growing peripheral axons 6 .…”
Here we describe a novel neuro-mesodermal assembloid model which recapitulates aspects of peripheral nervous system (PNS) development such as neural crest cell (NCC) induction, delamination, migration and sensory as well as sympathetic ganglion formation. The ganglia send neuronal projections to the mesodermal as well as the neural compartment. Axons in the mesodermal part are associated with Schwann cells. In addition, peripheral ganglia as well as nerve fibers interact with the co-developing vascular plexus, forming a neurovascular niche. Finally, developing sensory ganglia show response to capsaicin treatment indicating their functionality.The presented assembloid model could help to uncover mechanisms of NCC delamination, migration and PNS development in the human tissue context. Moreover, the model could be used for toxicity screenings or drug testing. The co-development of mesodermal and neuroectodermal tissues and of a well-organized vascular plexus along with a peripheral nervous system allows to investigate the crosstalk between neuroectoderm and mesoderm and between peripheral neurons/neuroblasts and endothelial cells. Such interactions influence NCC delamination and migration, sensory neuron differentiation and rearrangement of the primitive vascular plexus in the embryo.
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