Celia Herrera-Rincon
Herrera-Rincon worked with Michael Levin on Xenopus embryos whose brains were surgically removed early in development. The work showed that the young brain shapes muscle and nerve patterning far from the head12. A later study found that the developing brain also bears on innate immunity and on the behaviour of myeloid cells56.
- In the library
- 4 works, named in 7 passages elsewhere
Brainless Xenopus embryos
The method was a simple surgical removal of the early brain, after which the animal kept developing. Embryos without a brain showed abnormal somites and disordered trunk muscle fibres, and their tails were highly bent. Peripheral nerves also grew in an intense, disorganised way through the body2. The 2018 review stresses that these defects lay far from the brain, so local mechanical damage was not the likely cause. It argues instead for long-range signals that deliver developmental information to remote tissue4. The 2017 paper summarises the result as a need for the early brain in normal muscle structure at a distance1.
Drug and ion channel rescue
The 2017 paper tested whether the brain's role could be replaced by pharmacology. Scopolamine, which blocks the muscarinic acetylcholine receptor, partly counteracted the effects of a teratogen in brainless embryos. Highly aberrant phenotypes fell from 92% to 15%, though muscle did not fully return to the control pattern3. The 2018 review adds that scopolamine given after brain removal prevented muscle defects, and that expression of the HCN2 ion channel also counteracted them. It reads these results as showing that a normal brain protects patterning from drug-induced damage, and that neurotransmitter and bioelectric signals can mimic some brain functions4.
Immunity and later citation
The 2020 paper used the same brainless model to ask about infection. It built on the earlier finding that the nascent brain instructs muscle and nerve patterning5. In brainless embryos, myeloid cells formed rows of flattened cells that followed the internal nerve network, a pattern absent in controls6. Other authors have cited the work. Levin cites the 2017 and 2018 papers for the need of a functional nervous system in correct patterning7. McMillen and colleagues cite the 2020 paper as evidence that removing central nervous input can alter macrophage behaviour8.
Taken together, these results clearly indicate the importance of the early embryonic brain for normal development of muscle structure occurring at considerable distance.
Herrera-Rincon C, Herrera-Rincon C, Pai VP, Moran KM…, 2017 · The brain is required for normal muscle and nerve patterning during early… · open at passage 12Absence of the early brain leads to muscle and peripheral nerve mispatterning (defects). Animals that developed without a brain exhibited abnormal patterns of segmented embryonic tissues known as somites
Herrera-Rincon C, Levin M, 2018 · Booting up the organism during development: Pre-behavioral functions of the… · open at passage 4We found that in the absence of a brain, scopolamine treatment partially counteracted the teratogenic effects of RS (Scopo+, Supplementary Fig. 3A–C).
Herrera-Rincon C, Herrera-Rincon C, Pai VP, Moran KM…, 2017 · The brain is required for normal muscle and nerve patterning during early… · open at passage 27Importantly, the observed defects occurred in areas very far from the brain, suggesting that the effect is not simply due to local mechanical damage that can affect morphogenesis in that region.
Herrera-Rincon C, Levin M, 2018 · Booting up the organism during development: Pre-behavioral functions of the… · open at passage 8Our prior research into brain-dependent developmental signaling revealed that the nascent brain, even before being fully formed, plays an instructive role in patterning somitic muscle and peripheral neural networks.
Herrera-Rincon C, Paré JF, Martyniuk CJ, Jannetty SK…, 2020 · An in vivo brain-bacteria interface: the developing brain as a key regulator of… · open at passage 4myeloid cells of BR– exhibited different morphology, with respect to other areas or to Ctrl embryos, with rows of flattened cells, compatible with a macrophage-like network
Herrera-Rincon C, Paré JF, Martyniuk CJ, Jannetty SK…, 2020 · An in vivo brain-bacteria interface: the developing brain as a key regulator of… · open at passage 25The 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
Levin M, 2019 · The Computational Boundary of a "Self": Developmental Bioelectricity Drives… · open at passage 82there is also a growing body of evidence that bioelectric manipulation either via chemicals (Paré et al., 2017) or removal of central nervous system (Herrera-Rincon et al., 2020) input can alter macrophage behavior
McMillen P, Oudin MJ, Levin M, Payne SL, 2021 · Beyond Neurons: Long Distance Communication in Development and Cancer · open at passage 29
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