In this article, it is pointed out with integrative analysis that organogenesis manifests limitation in time and possession of termination, while infinite cell proliferation called as cancer and tumor is lethal. Besides, it is reversely demonstrated from a few notable constant outgrowing skin derivatives that termination is required for organogenesis inside the animal. Accordingly, it is suggested that the requirement for organogenetic termination would be the new intrinsic constraint for animal development and heredity. In further, it is suggested from comparative analysis that this new intrinsic constraint would not influence the temporal and spatial reorganization of morphogenesis, but place restrictions on alteration of organogenetic mechanisms themselves. Especially, it is pointed out that addition of new induction mechanism or elimination of termination mechanism would usually cause endless organogenesis and lethality, subjecting to restriction by the intrinsic constraint, while addition of new termination mechanism or elimination of induction mechanism not be affected by the intrinsic constraint, occurring more frequently in evolution. In accordance, it is identified this intrinsic constraint as the pertaining cause for frequent occurrence of developmental parallelism and terminal addition in animal evolution as recapitulation. In this article, it is also provided with some animal models to demonstrate the evolution of organogenetic termination as key developmental control, such as the hair and nail in humans, the sexual dimorphism in mammary glands, the epidermal scale in reptiles, the tail metamorphosis in amphibians, and the variation in limb digits in vertebrates.
The study of development was dominated by the principle of recapitulation or biogenetic law in 1800s, as represented by Haeckel and von Baer. Nonetheless, as some exceptions have accumulated, the hypothesis of recapitulation is no longer universal [
Most types of differentiated tissue cells were present early in animal evolution. Even the very primitive metazoan groups possess several cell types. The differentiated tissue cells of muscle, nerve, gut and epithelium among various animal species appear to be very ancient in origin and the majority of them to remain relatively stable during the long period of evolutionary process [
Development is complex and comprises many different processes, including morphogenesis and differentiation. All organs are made of tissues, while organogenesis is actually the process of tissue formation and organization for the generation of an organ. Differentiation of tissues may also constitute a part of morphogenesis in some organs, such as the formation of bone and tooth, while differ in process from organogenesis in else, such as the synthesis of neuronal transmitters.
It is common knowledge that there are four types of tissues constituting the organs of animals, which are the nervous tissue, connective tissue, muscular tissue and epithelial tissue. The morphology of individual tissues is determined by the morphological constituents at cellular level, namely the cell number, position, shape and sometimes the secretes, manifesting also as four in cellular characteristics. For intuitive demonstration, the neuron number in cortex determines the cortical modality number in mammals, the neuron position in cortex arranges neurons into various laminates, and the neuron shape contributes to the formation of synapses and neuronal interactions [
In correspondence, morphogenesis of a tissue or organ also involves four cellular processes respectively as cell proliferation/elimination, migration, shaping and secretion. For intuitive demonstration, in the development of mammalian cortex [
Morphogenesis of an organ is initiated by inductive events. There are many types of inductive events. Some inductive processes occur very early in the gastrula stage and may be involved in the establishment of rudimental body plan. Organogenesis proceeds on the subsequent inductive events, initiating cell proliferation, migration, shaping and secretion for the generation of an organ. When reaching appropriate size and shape, morphogenesis of the organ terminates.
The cellular process of organogenesis manifests limitation in time and possession of termination, which is a common phenomenon widely present in all four types of tissues constituting the organs of animals. With regard to the nervous tissue, in the morphogenesis of cerebral cortex in monkeys, cortical neurogenesis starts around the 40th embryonic day, but stops at the 70th embryonic day in the limbic cortex and 100th embryonic day in primary visual cortex [
In addition, programmed cell death sometimes helps modify the final shape of some organs into appropriate for use, such as the digit separation in limbs [
More importantly, if viewed at the organizational level in animals, termination of morphogenesis of organs in further plays a key role in controlling organogenesis more than induction. Without termination, morphogenesis of an organ would proceed infinitely, disorganizing the overall morphology and causing lethality, especially with excessive cell proliferation and secretion. Infinite cell proliferation due to loss of contact inhibition is called as cancer [
A few notable exceptions to this intrinsic constraint deserves special attention, in which constant cell proliferation or secretion occurs on the surface of body, mostly as skin derivatives, so that no longer disrupts the internal organization and overall morphology of animal. The epidermal scales in reptilian species are continually thickened due to continual proliferation of epidermal cells, with the outer layer of the epidermal scales shed in lizards and snakes [
In collection herein, termination is special in that it is intrinsically required for animal development and heredity to prevent endless organogenesis and congenital dysmorphosis, which is supported in three aspects: 1) Organogenesis manifests limitation in time and possession of termination, which is widely present in all four types of tissues in animals, except in a few constant outgrowing skin derivatives. 2) Infinite cell proliferation called as cancer and tumor is lethal, while whales with skeleton growth more than terrestrial animals can only live in ocean but would die on land from skeleton overloading. 3) The few notable skin derivatives of constant cell proliferation or secretion on the surface of body reversely demonstrate that cell proliferation or secretion within the body of animal must in turn be terminated for development and heredity to avoid endless organogenesis and congenital dysmorphosis.
Genetic changes of animal morphogenesis can be classified into two categories. One category of morphogenetic changes may only involve the temporal or spatial reorganization of the existing morphogenetic processes, while another category of morphogenetic changes directly involve the alteration in nature of organogenetic mechanisms themselves.
Genetic changes involving only the temporal and spatial reorganization of existing morphogenetic processes occurred often in animal evolution. There have been efforts to create some temporal models to demonstrate the heterochrony with changes in time of developmental events in animals [
Genetic alteration in the nature of organogenetic mechanisms themselves may also cause changes in morphology of animal, which is more easily demonstrated with genetic and comparative studies at molecular and cellular level. To further distinguish this concept from the temporal and spatial reorganization of existing morphogenetic processes, it is herein to inspect the development of mammary glands. On the one hand, there are different numbers of mammary glands in various mammals which may even be located at different positions on the abdominal surface of body. Changes in location of mammary glands in evolution just represent spatial translocation of mammogenesis. On the other hand, during mammary development, the vigorous proliferation of ducts and alveoli in pregnancy and lactation may be induced by several hormones, notably by growth hormone, prolactin, placental lactogen and so on [
Genetic changes involving the nature of organogenetic mechanisms themselves may in further be classified into several forms in animals. Changes in mechanisms of organogenesis may introduce a new organogenetic mechanism, eliminate some existing mechanisms, and may also change an existing mechanism into another novel mechanism. In fact, the latter form of change in mechanism can be understood as simultaneously introducing a new mechanism while disrupting an existing mechanism. In this regard, all changes in mechanisms of organogenesis in animals can ultimately be classified into the two forms as introduction of a new organogenetic mechanism and elimination of some existing organogenetic mechanisms. The above mentioned evolutionary acquisition of pregnancy-controlled cellular proliferation in mammary glands was the introduction of a new inductive event, whereas the constant growth of human hair instead resulted from the evolutionary elimination of termination in growth of original short hair in apes as neutral genetic mutation adaptive to mechanical cutting, as manifested in many national and world records on length of human hair.
In brief, genetic changes of animal morphogenesis can be classified into two categories. One may only involve the temporal and spatial reorganization of existing morphogenetic processes, while another involves the changes in nature of organogenetic mechanisms themselves.
As the genetic changes of morphogenesis can be classified into two categories either as the temporal/spatial reorganization of existing morphogenetic processes or as the changes in nature of organogenetic mechanisms themselves, it is interesting to inspect the different effects of this intrinsic constraint on the two categories of morphogenetic changes during animal evolution.
With regard to the genetic changes as temporal and spatial reorganization of existing morphogenetic pro- cesses in animals, organogenesis in descendents would certainly be terminated in the same way as in progenitors. No matter in the cases fitting in the temporal models created by some scientists recently [
The intrinsic constraint requiring organogenetic termination would place some new restrictions on alteration of organogenetic mechanisms themselves in animal evolution, which is easily demonstrated with genetic and comparative studies at molecular and cellular level. Addition or alteration of an induction mechanism for organogenesis would have to be confronted with the requirement of termination against the organogenesis initiated by the newly introduced induction in animals. Without termination, the newly acquired organogenetic process would also proceed infinitely and cause lethality. In this regard, requiring termination would exert an additional constraint on genetic addition or alteration of induction mechanisms for organogenesis. However, in a few special cases, a new induction mechanism may have been introduced in animal evolution as it just happened to be able to make use of some existing mechanisms for termination. For instance, as stated above, the cellular proliferation in mammary duct and alveolus was the consequence of genetic addition of novel organogenetic induction by pregnancy and lactation [
Some inductive events for other purposes may occur at earlier developmental stages than the induction of organogenesis, such as the determination of cell fates at the earliest embryonic stages, the establishment of rudimental body plan and so on. Changes in these early induction mechanisms rather than organogenetic induction are irrelevant to the intrinsic requirement of organogenetic termination to stop the organogenesis initiated by organogenetic induction, so that would not be restricted by this intrinsic constraint on animal development and heredity. For instance, the direct-developing sea urchin without larval stage may have evolved from indirect- developing sea urchins with larval stage through extensive remodeling in early stage in localization of maternal determinants in oocyte and dissociation of cell cleavage from axis formation [
It is important to point out that addition of an induction mechanism of organogenesis via duplication of an existing induction mechanism should certainly be able to make use of the termination mechanisms of original organogenesis, and would have occurred more frequently in animal evolution without affected by the intrinsic constraint requiring organogenetic termination, which is a part of developmental parallelism in evolution some authors adopted to account for organogenetic recapitulation [
Addition of new termination mechanisms to the existing organogenetic processes in animals would make the descendents possess more termination mechanisms for stopping organogenesis than their progenitors, so that not be affected by the intrinsic constraint requiring organogenetic termination. In higher mammals, although the mammary rudiments develop in both sexes in their embryos, the morphogenesis of mammary glands in male embryo is terminated early in response to testosterone before the formation of any ductal structures, while it still continues in female embryo due to the lack of testosterone [
Addition of accessory termination mechanisms should not be constrained by the intrinsic requirement for organogenetic termination either, as the descendents would likewise possess more termination mechanisms to stop organogenesis than their progenitors. Some functional larval structures of amphibians such as the tail of tadpole are absorbed as a whole during metamorphosis with programmed cell death [
As the intrinsic constraint requiring organogenetic termination has not placed any restrictions on evolutionary addition of new termination mechanisms and accessory termination mechanisms, addition of these mechanisms would certainly have occurred frequently in animal evolution. This is exactly the pertaining cause of terminal addition of developmental processes in animal evolution some authors termed [
It is necessary to point out that exposure to environmental adaptation or natural selection is not the reason for causing terminal addition. As having been demonstrated, duplication of the earlier organogenetic induction also occurs freely and is terminated as in original, which is obviously also subject to environmental adaptation or natural selection.
Herein, it is accounted for the developmental parallelism and terminal addition as two branches of recapitulation with the intrinsic constraint requiring organogenetic termination. Recently, it was demonstrated with computational system that recapitulation indeed occurred as higher in frequency during animal evolution [
In contrast, elimination of organogenetic mechanisms has been less studied in comparison to addition. Elimination or disruption of organogenetic induction would lead to deletion of the whole subsequent organogenetic processes initiated by the inductive event in animals, so that it would not cause endless organogenesis, nor be restricted by the intrinsic constraint requiring organogenetic termination. It has been shown that the evolutionary loss of teeth in birds was the result of dysfunction in induction mechanism for tooth morphogenesis [
Nonetheless, as the organogenetic termination functions to stop organogenesis, elimination of termination mechanisms would have to run the risk of causing endless organogenesis. In this regard, the intrinsic constraint requiring organogenetic termination would place restrictions on elimination of organogenetic termination, making the animal die and disappear. Nonetheless, when the resulted constant organogenetic growth happened on the body surface protruding outward without causing morphological disorganization, elimination of termination may be observed in animal evolution. It is common knowledge that the human skull hair can grow continuously in length if not cut mechanically, as manifested in many national and world records on length of it. It was evolved from the short hair in apes, and was obviously acquired in human evolution as elimination of termination for hair growth via mutations neutral to mechanical cutting. Similar story occurred to the evolutionary acquisition of constant growth of human nail with many national and world records on length of it too.
Elimination or disruption of accessory termination mechanisms may not necessarily eliminate (primary) termination against organogenesis, nor cause endless organogenesis, so that nor necessarily be restricted by the intrinsic constraint requiring organogenetic termination. In vertebrate limb development, interdigital cell death is the accessory termination mechanisms helping to separate digits. Partial dysfunction of this process in web-footed birds, as characterized by smaller scale and shorter duration, has not led to endless limb growth but just annealed the toe digits [
In brief, the various genetic changes in organogenetic induction and termination during evolution are summarized in the following table with regard to the constraint requiring organogenetic termination.
The new constraint requiring termination for organogenesis would significantly deepen the hereditary understanding of animal development and evolution. It is a new hereditary constraint for animal development, which potentially benefits to the therapeutic research of cancers and tumors, the biomedical research on organ regeneration from stem cells, the biological research in developmental control and adaptive skin derivatives, and so on. It is also a new hereditary constraint for animal evolution, which not only accounts for the recapitulation as the frequent occurrence of developmental parallelism and terminal addition in animal evolution, but also potentially becomes a more general rule than recapitulation in providing explanations to the organogenetic exceptions of recapitulation as degenerative elimination of inductive or accessory termination mechanisms.
Due to the importance of organogenetic termination, it is necessary to choose some valuable animal models for further genetic and comparative studies at molecular and cellular level in future. The hair and nail in humans versus in primates, the sexual dimorphism of mammary glands in mammals, the epidermal scale in reptiles, the metamorphosis of tail in amphibians, as well as the variation in limb digits in vertebrates are all good models for demonstration of genetic variations in organogenetic termination in animals.
In this article, it is pointed out that the cellular processes of organogenesis manifest limitation in time and possession of termination, which is widely present in all four types of tissues constituting the organs of animals. Without organogenetic termination, organogenesis would usually proceed on infinitely and result in lethality. Infinite cell proliferation from mutations is called as cancer and tumor, and is lethal. Cancers and tumors occur in most organs, demonstrating the proliferative potency of the organs. Besides, the few notable cases of constant cell proliferation or secretion on the surface of body as skin derivatives also reversely demonstrate that cell proliferation or secretion within the body of animal must in turn be terminated for development and heredity to avoid endless organogenesis and congenital dysmorphosis. In accordance, requirement for organogenetic termination is a new intrinsic constraint on animal development and heredity.
This intrinsic constraint requiring organogenetic termination would not affect the genetic changes only involving the temporal and spatial reorganization of morphogenesis in animal evolution. Nonetheless, the new intrinsic constraint would place some restrictions on alteration of organogenetic mechanisms themselves in evolution. Addition of new induction mechanism or elimination of termination mechanism in animals would usually cause endless organogenesis and be lethal, so that be restricted by this intrinsic constraint, except the newly added inductive mechanisms happened to be able to make use of the existing mechanisms for termination or the endless organogenesis with termination mechanism eliminated happened to situate on the surface of body without disturbing the overall organization of morphology. It is necessary to point out that change in inductive events for purposes other than organogenesis at earlier developmental stages is irrelevant to the intrinsic requirement of organogenetic termination to stop the latter organogenesis initiated by organogenetic induction, so that would not be restricted by the intrinsic constraint.
In contrast, duplication of existing induction mechanism would certainly be able to make use of the existing termination mechanisms against organogenesis, nor be restricted by this intrinsic constraint, so that occurred more frequently in evolution. Likewise, addition of new termination mechanism would not be restricted by this intrinsic constraint either, nor would the change in accessory termination mechanisms necessarily be restricted by the intrinsic constraint, so that also occurred more frequently in evolution. In this regard, this intrinsic constraint requiring organogenetic termination is identified as the pertaining cause for the frequent occurrence of developmental parallelism and terminal addition in animal evolution as recapitulation. Besides, the intrinsic constraint requiring organogenetic termination in further enriches our knowledge on genetic elimination of organogenetic mechanism as either induction or termination during animal evolution.
In this article, it is provided with some valuable animal models to demonstrate the evolution of organogenetic termination as key developmental control, such as the hair and nail in humans versus in primates, the sexual dimorphism of mammary glands in mammals, the epidermal scale in reptiles, the metamorphosis of tail in amphibians, and the variation in limb digits in vertebrates, making it convenient for genetic and comparative studies at the molecular and cellular level.
The author would like to express his gratitude to Mingxun Cai for his granting to pay for the Open Access charge of this paper.
The author declares that there is no other financial support, nor conflict of interest for this paper. The core thought expressed herein in this theory was initially formed in mind in 1987 without publication when the author was a graduate student at University of Notre Dame in USA.
Zi-Jian Cai, (2015) Termination of Organogenesis as Intrinsic Constraint on Animal Development and Evolution: A Theory. Open Access Library Journal,02,1-9. doi: 10.4236/oalib.1101646