The central nervous system, essential for vertebrate development

The central nervous system, essential for vertebrate development

Erection of multicellular structures needs something that unicellulars do not: huge amounts of information for the strictly determined spatial arrangement of a myriad of cells of different types and a mechanism for transmitting that information to the offspring.

Transmitting huge amounts of epigenetic information from parents to the offspring is a prerequisite for complex multicellular life.

The genetic information encodes proteins, but there is no indication, let alone proof, that it determines the specific spatial arrangement of billions or trillions of cells of various types in the animal body. The amount of information contained not only in genes but in the whole metazoan genome, including the “junk” DNA, quantitatively represents only a negligible fraction of the information necessary for molding an animal structure.

A human brain alone has at least one trillion nerve cells. Before birth, that is experience-independently, each neuron establishes an average of 10,000 specific connections with specific neurons, implying that information for establishing these connections alone is of the order of quadrillions of bits, millions of times greater than the total amount of information contained in the genomic DNA.

The Control System and the Epigenetic System of Heredity in Metazoans

How can an organism, whose structure at the molecular, cellular, and supracellular levels is continually disintegrating, succeed in maintaining that complex structure and function during its lifetime? Metazoans succeed in doing so unambiguously proves that they

– Continually monitor the state of the system,
– Figure out structural losses, based on the presence of information about the normal
structure,
– Figure out restitutive necessities, and
– Start signal cascades and activate GRN for replacing the lost structures at the right time
and place.

The maintenance of multicellular structures imply possession by the control system of information on the normal structure.

Question: How did this control system emerge ? Did it not require to have a priori " knowledge " of the normal structure? Does monitoring and figuring out based on a control system which constantly compares the actual state to what it has to be, as used in engineering,  not require the previous input of information, both, of how the correct homeostatic situation has to be, and how to control that state of affairs, and in case of disease and homeostatic imbalance, how to activate signal cascades in order to replace the lost structures?  Are engineering, monitoring, figuring out, controlling not all activities exclusively performed by intelligence?  

The above functions performed by metazoans are typical functions of control systems, in principle similar to the control systems used in engineering. No metazoan would exist as such in absence of a control system. The presence of a control system is one of the fundamental features of living, as opposed to anorganic, systems. That control system makes possible the development and maintenance of the metazoan organism, a thermodynamically improbable structure.

In metazoans, this is an integrated control system (ICS) with the central nervous system CNS as its controller. During reproduction, the integrated control system (ICS)  serves as the epigenetic system of heredity, which controls individual development. This epigenetic system organizes cells in the supracellular multicellular structures, parts, and organs, and the morphology in general.

In the process of metazoan reproduction, the integrated control system (ICS) functions as the epigenetic system of heredity. The individual development from the egg/ zygote to adulthood is a bigenerational process in which early development from the unicellular stage to the phylotypic stage takes place based on the epigenetic information provided parentally to the gametes.

In the second, the postphylotypic stage, the embryo is in possession of an operational CNS, which generates and provides information for the rest of the individual development, organogenesis and morphogenesis. After the phylotypic stage, electrical signals resulting from the processing of external/internal stimuli in neural circuits in the CNS (neural net in lower invertebrates) determine the activation of specific signal cascades leading to the development of specific morphological traits. The epigenetic information for metazoan morphology is computationally generated in the CNS by processing the input of internal/external stimuli.

Ample empirical evidence shows that the inductive signals for the development of tissues and organs during individual development originate in the CNS. During the adult life, as well, signal cascades for the maintenance of animal morphology and homeostasis come from the CNS, via neuroendocrine cascades, often with essential participation of the local innervation.

Development of the metazoan structure requires a considerable investment of matter, free energy, and information. With matter and free energy taken from the environment in the form of food, where does the information for the individual development and restitution of the disintegrating metazoan’s supracellular structure come from? That is, the source of the information necessary for the prenatal, i.e., experience-independent, the establishment of trillions or quadrillions of specific connections among neurons?  Biologists believe that this information resided in the nervous system, but that does not answer the origin or source of the information. The development of various organs during embryogenesis is induced from signals and signal cascades originating in the central nervous system CNS. But the meaning of these signals, and the interpretation of those, had to be pre-programmed, and pre-established. 1

Since instructional complex information comes always from intelligence, i would say, most probably, the information was pre-programmed by the intelligent designer.

1. Epigenetic principles of evolution, 2011, page 24

https://reasonandscience.catsboard.com/t2929-the-central-nervous-system-essential-for-vertebrate-development



In thousands of experiments, it has been demonstrated that spontaneous and induced mutations lead to anomalies in morphology, physiology, and behavior. We know of numerous genes in various species of invertebrates and vertebrates that are clearly related to specific characters. No one can deny that mutations, deletions, or generally nonfunctioning and malfunctioning genes lead to specific abnormal morphologies.

In other words, it is correct to say that in metazoans the normal gene is a necessary condition for the development of a specific normal character, but it would be logically erroneous to grant the “necessary conditions” attributes of the cause when these conditions are not sufficient for the development of normal morphology.

The development of phenotypic characters in metazoans is a function of signal cascades and gene regulatory networks (GRNs) with each network comprising from several to hundreds of genes. The presence of each of these genes is a necessary condition for the normal development of the specific character, but none of these genes is the cause of that character.

Moreover, even these several to hundreds of genes, in their entirety, do not rise to the level of a cause. Contemporary biological knowledge says that GRNs generally represent downstream entities of signal cascades that are activated by neurohormonal signals, and the primary source of the information for starting these signal cascades is a chemical output released as a result of the processing of electrical signals into which all external and internal stimuli are converted in neural circuits.

Signal cascades represent causal chains in which the preceding event is the cause of the next event. One cannot reasonably talk or think about the cause of a phenotypic result determined by such signal cascades. But we can instead distinguish between the last link in the causal chain, which is the proximate cause of the phenotypic result and the first (or initiating) link, which is the ultimate cause.

To single out a particular gene as the cause of the phenotypic character in such cases is to attribute to the part the functions of the whole.

The fact that the signal cascades that activate GRNs start with electrical/chemical outputs of the processing of internal/external signals in neural circuits suggests
that the activation/inactivation of GRNs is determined by the computational activity of neural circuits, which ultimately determine whether, where, and when to turn
on/off GRNs

In 1953, Watson and Crick published the seminal science paper :

MOLECULAR STRUCTURE OF NUCLEIC ACIDS
http://dosequis.colorado.edu/Courses/MethodsLogic/papers/WatsonCrick1953.pdf

In 1962, they received the Nobel prize "for their discoveries concerning the molecular structure of nucleic acids and its significance for information transfer in living material."
https://www.nobelprize.org/prizes/medicine/1962/summary/

Then, in 1969, Davidson and Roy Britten from the Carnegie Institution in Washington, together, they formulated a hypothesis of gene regulation in complex multicellular
animals, summarized in a theoretical paper entitled

Gene Regulation in Higher Cells: a Theory,” published in Science
https://sci-hub.tw/https://www.ncbi.nlm.nih.gov/pubmed/5789433

This influential paper, based on data from Drosophila and other organisms, proposed a mechanism of gene regulation in which transcription factors controlled expression of gene batteries.
http://www.nasonline.org/publications/biographical-memoirs/memoir-pdfs/davidson-eric.pdf

So that was information on top of information.




Another epigenetic Code, the neuronal spike-rate Code, essential for embryonic development, comes to light.

In 1953, Watson and Crick published the seminal science paper: MOLECULAR STRUCTURE OF NUCLEIC ACIDS. 1 In 1962, they received the Nobel prize "for their discoveries concerning the molecular structure of nucleic acids and its significance for information transfer in living material." For a long time, it was believed, that genes define phenotype.  Then, in 1969, Davidson and Roy Britten from the Carnegie Institution in Washington, together, formulated a hypothesis of gene regulation in complex multicellular animals, summarized in a theoretical paper entitled: Gene Regulation in Higher Cells: a Theory,” published in Science 2 This influential paper, based on data from Drosophila and other organisms, proposed a mechanism of gene regulation in which transcription factors controlled expression of gene batteries. 3 This shifted the explanation of organismal form from genetic, to genetic AND epigenetic information. The architecture of the body plan depends, amongst other factors,  on the structure of developmental gene regulatory networks. So, the extended evolutionary synthesis has expanded, shifted, and attempted to incorporate the new findings but ultimately always attributing everything to evolutionary unguided natural forces.  Further scientific discoveries in the field of epigenetics are demonstrating that the signal cascades that activate GRNs start with electrical/chemical outputs of the processing of internal/external signals in neural circuits which suggests that the activation/inactivation of GRNs is determined by the computational activity of neural circuits, which ultimately determine whether, where, and when to turn on/off GRNs. That adds ANOTHER layer of biological information. Its information above information.  Genes store information which needs epigenetic instructions on various levels that sum up,  on whether, where, and when they should be expressed.4

The activation/inactivation of genes, which are responsible for differentiation and coordination of activities of each cell with other cells, is regulated by an integrated control system (ICS), with the central nervous system (CNS) as its controller. Neural signals, which, via the signal cascades, activate/inactivate these genes, ultimately, originate in the CNS. The CNS can accomplish such a huge and extremely complex task: provision of information for gene activation/inactivation to billions/trillions of cells throughout the animal body.

In the case of gene activation under the influence of external stimuli, but internal stimuli as well through estrogens and other hormones, no direct physical contact exists between the gene and the stimulus that triggers its expression. This is remarkable: the stimulus induces the expression of the gene at a distance! It is not the stimulus per se but a neural product of the processing of the stimulus in the nervous system that, by activating a specific signal cascade, induces expression of a specific gene in the cell nucleus. The nervous system activates the signal cascade, which establishes a causal relationship between the stimulus and the stimulus-inaccessible gene. This expression of genes is a unique function of the neuron and the CNS, a property that does not exist in unicellular organisms.

The stimulus is taken as a message by exteroceptors, proprioceptors, and interoceptors converted into electrical, so-called spike trains (nongenetic symbols) and, in this form, transmitted to the CNS. By processing these electrical representations of stimuli, neural circuits generate chemical outputs (e.g., neurotransmitter, neuromodulator, neuropeptide), which essentially decipher the genetically meaningless stimulus into a message for expression of a particular gene or a number of genes. The CNS, thus, transforms a genetically inert stimulus into a gene inducer. Both the initial conversion of stimuli into electrical spike trains and their processing in neural circuits are computational nongenetic processes whose mechanisms are only little known.

Neural circuits, functional units of the nervous system, are ensembles of up to billions of neurons connected by trillions of specific synaptic contacts. By processing information coming from afferent neurons in the form of electrical signals, neural circuits perceive the “information generated by stimuli arising from both the external and internal environment,” which is one of the main functions of the brain and facilitate the transfer of information according to a neural, nongenetic code, which is represented by the spike rate of neurons.

Science does not know how information is dynamically represented by patterns of action potentials, or spikes, generated by neurons in relevant brain regions corresponding to moment-to-moment perceptions, memories, creative thoughts, and behaviors but also orchestrating the gene regulatory network and gene expression. Neurons encode information by changing firing rates.  The neural code—the rule under which information is signaled inside the brain, remains still a black box to be opened.  

Neural circuits release their output in the form of electrical or chemical signals (neurotransmitters and neuromodulators) that are discharged on neurosecretory cells of the “endocrine brain,” the hypothalamus, the pituitary, or, via nerve endings, directly to the target tissues and organs. These neural signals act as “instructions” (epigenetic information) for selectively activating specific algorithms or signal cascades ultimately leading to selective expression of particular gene(s) out of a variety of genes available for transcription.

The connection between the gene and the stimulus is communicative rather than direct and is computationally determined. As pointed out earlier, the processing in the nervous system establishes a causal relationship between the stimulus and expression of the gene, which otherwise would not exist.

Neural Processing of Stimuli Generates Information Development
Formation of primitive neural circuits in the embryo may be a function of parental epigenetic information provided with the gamete(s) as part of the development of the embryonic CNS.  Neurons from various regions of the CNS extend their axons to form connections with specific neurons, thus creating primitive functioning neural circuits. This process takes place in absence of electrical activity, based on the parental epigenetic information provided via gamete(s) and/or transplacental in placental organisms. The beginning of the spontaneous and sensory-driven electrical activity in response to the developing embryonic structure enables fine-tuning of the imprecise synaptic connections of the primitive neural circuits.

The huge and dynamic network of the embryonic neuronal connections established during embryogenesis, before the embryo starts communicating with the external environment, may be necessary for generating the morphological information for development, organogenesis, and morphology in metazoans. The overwhelming majority of these connections are determined by the electrical activity and computational activity of the CNS during the individual development, in response to the input of internal/external stimuli.

Where might that tremendous amount of information necessary for histogenesis and organogenesis, for erecting the immensely complex metazoan structure after the phylotypic stage, come from? The fact that exactly at this juncture, when parentally provided epigenetic information is exhausted, the embryonic CNS becomes functional (i.e., starts patterned electrical activity) might not be a sheer coincidence.
The embryonic CNS, the brain and the spinal cord, is the source of numerous inductions for the development of organs and parts of the embryo. The electrical activity of the CNS, and the synaptic morphology related to it, are necessary for the embryonic development.

As we can see, there are several layers of interdependent information, which work in a joint-venture, to promote embryogenesis, and organismal development. Rather than unraveling the origin of such complexity by natural means, more and more different epigenetic codes are unraveled by science. 

1. Without information, the inflow of energy would not lead to self-organization. Information in this sense is more than information in the Shannon and Weaver (1949 ) sense; it is functional and can be thought of as information in both an “ instructional ” and “ control ” sense, as it requires information that creates complex structures and metabolic pathways that productively channel the flow of energy both within an organism and between the latter and its environment.
2. Blueprints, instructional information, and master plans, which permit the autonomous self-organization and control of complex metazoans upon these are both always tracked back to an intelligent source which made both for purposeful, specific goals.
3. The Blueprint and instructional information stored in DNA, together with epigenetic codified instructional information, which directs the make and controls biological cells and organisms - the origin of both is, therefore, best explained by intelligent design.


Simplified diagram of the fashioning of a relationship between the external stimulus and a particular gene.
An external stimulus is received from specific neurons of the sensory organ. Receptor neurons convert the stimulus into a train of electrical spikes and, in this form, transmit it to a specific neural circuit for processing or interpreting. The mechanism of processing is still almost a black box. What we know is the output of the processing, which is an electrical/chemical signal that leads to selective activation of a specific algorithm or adaptive signal cascade out of a number of cascades (1–6) that the secretory neuron can potentially activate.

Electrical activity is responsible for sculpting circuits computationally, and that activity might represent a pre-programmed property of self-organization.

During embryonic development, each of ~1 trillion mammal cortical neurons establishes specific connections with an average of 10,000 other neurons, leading to the formation of the cortical networks. The immature neuronal networks apparently use the inherited information and the input of information from the developing embryonic structure for generating epigenetic information in an experience-independent mode.

The central idea developed in this section is that the establishment of the early neural networks, coinciding with the termination of the activity of parental cytoplasmic factors (epigenetic information) at the phylotypic stage, as part of the early embryonic development, is determined by the regulatory activity of the parental epigenetic information provided with gametes (and also transplacental in placental mammals). The huge amount of the epigenetic information necessary for organogenesis is generated by the embryonic CNS, which is operational from the phylotypic stage forward.






1. http://dosequis.colorado.edu/Courses/MethodsLogic/papers/WatsonCrick1953.pdf
2. https://sci-hub.tw/https://www.ncbi.nlm.nih.gov/pubmed/5789433
3. http://www.nasonline.org/publications/biographical-memoirs/memoir-pdfs/davidson-eric.pdf
4. Epigenetic principles of evolution, 2011, page 17

The fact that metazoan morphology is determined by developmental pathways during ontogeny suggests that adaptive changes in morphology will also be determined during ontogeny. And the fact that during ontogeny many developmental pathways for animal structures are activated by signals that ultimately start in the CNS suggests that the information necessary for adaptive changes of these structures may also originate in the CNS. Many discrete changes in metazoan morphology that are observed in numerous cases of phenotypic plasticity are induced by signal cascades starting in the CNS. The biological phenomenon of transgenerational plasticity, that is the appearance in the offspring of inherited morphological (usually adaptive) modifications in response to environmental stimuli that have affected their parent(s) comes in the form of brain signals. This fact, logically, suggests that the mechanism of the induction of adaptive change is probably a neural mechanism. The information necessary for inducing specific inherited changes in cases of transgenerational developmental plasticity is generated in the CNS and results from the processing of internal/external stimuli in neural circuits.

Mechanisms of the generation of the new information necessary for changes in developmental pathways represent a black box. We know “what” these neural circuits do, but we do not know “how.” In the initial link of the causal chain, we see the stimuli being encoded in sensory neurons in the form of electrical spike trains at the entrance of the black box and, at the other end, we see electrical and chemical outputs that activate specific signal cascades in the offspring.

Genetic and epigenetic mechanisms interact mutually, while genetic information is subordinated to epigenetic information. 

Adaptive changes in the phenotype (behavior, morphology, physiology, and life history) in metazoans start with complex neurobiological processes of reception, informational conversion, integration, and processing of external/internal stimuli in the neural system, the CNS or neural net, and investment in gametes of new epigenetic information for inducing specific changes in the developmental pathways in the process of individual development of the offspring.

The making of Morphology, developmental pathways,  ontogeny, and the process of individual development must come from somewhere. And so, pre-programmed adaptation triggering the specific change in a developmental pathway which results in second degree of speciation.