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A recent study in Xenopus laevis embryos showed that the very early brain has important functions long before behavior. While the nascent brain is being constructed, it is required for normal patterning of the muscle and peripheral nerve networks, including those far away from the head. In addition to providing important developmental signals to remote tissues in normal embryogenesis, its presence is also able to render harmless exposure to specific chemicals that normally act as teratogens. These activities of the early brain can be partially compensated for in a brainless embryo by experimental modulation of neurotransmitter and ion channel signaling. Here, we discuss the major findings of this paper in the broader context of developmental physiology, neuroscience, and biomedicine. This novel function of the embryonic brain has significant implications, especially for understanding developmental toxicology and teratogenesis in the context of pharmaceutical and environmental reagents.
Figure 1. The processes of embryogenesis instructing patterning form a closed-loop control system between the brain and the body. A schematic drawing of a developing Xenopus embryo, representing how the embryonic brain (purple) is receiving instructive inputs from different (distal and proximal) body tissues to help building the right brain parameters (for example, shape and size). We have recently shown that this control operating system is bi-directional. The very early brain itself has, in turn, an instructive role on morphogenesis and patterning of remote tissues, such as peripheral neural network (blue) and somitic myotome (green). This closed-loop between brain and body is the earliest example of scaling and effective communication for self-assembly of complex biological structures
Figure 2. Functions of the very early brain include guiding and protecting correct embryo morphogenesis, which can be mimicked by ectopic expression of ion channels. Comparative images of muscle (A-C, under polarized light) and nerve (D-F, revealed by immunofluorescence against acetylated-alpha tubulin) structures of embryos that developed with a brain (Control), embryos that developed without a brain (Brainless), and embryos that developed without a brain and were injected with messenger RNA encoding the HCN2 ion channel (Brainless + HCN2 Inj). The absence of a brain during development leads to abnormal development of the muscles and the peripheral nerves, at considerable distances from the head, with disorganization of the body plan, myotomes lacking proper angles (magenta-dashed line in B), alterations in somite length (represented by two-headed arrows) and ectopic growth of nerve tissue (yellow arrows in E). By manipulating bioelectricity, for example via the mis-expression of HCN2, rescues the devastating muscle and nerve mispatterning that occurs in brainless animals (turquoise arrows in C, F). Rostral is right and dorsal is up. Scale bar = 100 μm. G, H. The effects of the drug (RS)-(tetrazol-5-yl)glycine during development depends on the presence or absence of the nascent brain in the embryo. While exposure to this drug does not cause developmental defects in control embryos (turquoise arrows in G indicate correct tail phenotype), it leads to severe deformities (yellow arrows in H demarcate bent spinal cord and tail aberrations) when the brain is not present to protect. Rostral is left and dorsal is up. Scale bar = 1 mm.
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