The brain is required for normal muscle and nerve patterning during early Xenopus development

Abstract

Possible roles of brain-derived signals in the regulation of embryogenesis are unknown. Here we use an amputation assay in Xenopus laevis to show that absence of brain alters subsequent muscle and peripheral nerve patterning during early development. The muscle phenotype can be rescued by an antagonist of muscarinic acetylcholine receptors. The observed defects occur at considerable distances from the head, suggesting that the brain provides long-range cues for other tissue systems during development. The presence of brain also protects embryos from otherwise-teratogenic agents. Overexpression of a hyperpolarization-activated cyclic nucleotide-gated ion channel rescues the muscle phenotype and the neural mispatterning that occur in brainless embryos, even when expressed far from the muscle or neural cells that mispattern. We identify a previously undescribed developmental role for the brain and reveal a non-local input into the control of early morphogenesis that is mediated by neurotransmitters and ion channel activity.

Preventing Ethanol-Induced Brain and Eye Morphology Defects Using Optogenetics

“…[32][33][34][35] Moreover, reinforcing these endogenous membrane voltage patterns rescues eye and brain defects caused by mutant notch and teratogen nicotine. 34,42,43 These experiments show that the bioelectric prepattern is necessary and sufficient for normal eye and brain morphogenesis as well as normal expression of the patterning genes.…”

“…[31][32][33][34][35]68 Reinforcing correct bioelectrical signals has been shown to rescue neural patterning defects caused by aberrant notch signals, mechanical damage, or exposure to neuro-teratogens such a nicotine. 34,42,43 Our previous work has extended the use of optogenetics to embryonic and regenerating tissues to more accurately control the timing and location of bioelectric intervention, 47,48 thus increasing our resolution as we study the intertwining of bioelectric events with second messengers and genetic regulatory networks. Building on these findings, we investigated optogenetic modulation of bioelectric signals for rescue of brain and eye malformations in a Xenopus model of fetal alcohol syndrome disorder.…”

The Computational Boundary of a “Self”: Developmental Bioelectricity Drives Multicellularity and Scale-Free Cognition

“…The evolution of neural control systems from pre-neural morphogenetic mechanisms suggests that there should be a lot of interplay between these systems in development. The requirement of a functional CNS for effective organ regeneration (Brockes, 1987) and for correct patterning in development (Herrera-Rincon et al, 2017;Herrera-Rincon and Levin, 2018) has been shown in a range of model species, and the tools of optogenetics can now be used to dissect the information content of nerve-mediated signaling as instructive cues for both normal morphogenesis and regulative development in which bodies adapt to major changes in architecture (Oviedo et al, 2010). 10.…”

The Biophysics of Regenerative Repair Suggests New Perspectives on Biological Causation

“…Critically, such discussions are often stymied by the desire to assign a single, reliable cause to a complex and stochastic fetal phenotype. Policy and pharmacological regulations would be revolutionized by a more nuanced, multifactorial notion of causation that replaced a binary expectation of cause and effect with the one that took into account the differential ability of some embryos to resist teratogens and the factors (like nervous system activity) that contributed to that capability.…”