Developmental Stability Research Articles

Associations Between Developmental Stability, Canalization, and Phenotypic Plasticity in Response to Heterogeneous Experience.

The processes of developmental stability, canalization, and phenotypic plasticity have ecological and evolutionary significance, and been studied extensively, but mostly separately and thus the relationships between them are not straightforward. Our objective was to better integrate these processes in the context of temporally heterogeneous environments. We did this by investigating the effects of early experience with temporal heterogeneity in water availability on associations between developmental stability, canalization, and phenotypic plasticity. We subjected eight plant species to a first round of alternating inundation and drought vs. constantly moderate water treatments (heterogeneous experience) and a second round of water conditions (to test plasticity). We measured fluctuating asymmetry (FA) in leaf size, intra- and inter-individual variation (CVintra and CVinter), and plasticity (PI) in traits and analyzed correlations between these variables across all species. Results showed little correlations between FA, CVintra and PI, several positive correlations between FA and CVinter in more stressful conditions, especially in as well as positive correlations between CVinter and PI initially and negative correlations between them later. These suggested the complexity of these relationships, which can depend on whether plasticity occurs. Greater inter-individual variation will more likely cooperate with plasticity before or during plastic response, whereas higher canalization may reflect phenotypic convergence. Both higher FA and CVintra can reflect faster growth, while CVintra may also reflect plant growth stage, and the two mechanisms should cooperate in response to environmental challenges. The complexity of these relationships suggests plants deal with environmental variation in elaborate and integrative ways which can be affected by many factors.

Developmental noise, entropy, and biological system condition.

Developmental noise is considered as a permissible level of entropy, as a compromise between the cost and needed precision of the realization of genetic information. In terms of entropy, noise is a measure of acceptable level of disorder to ensure a reliable system operation. Developmental noise plays a role in the observed phenotypic diversity and is associated with other indicators of the biological system condition. The thermodynamic characteristic of entropy by the energy metabolism also turns out to be related to the developmental noise. Phenotypic variability is largely determined by developmental homeostasis, including both canalization (an ability to form a similar phenotype under different conditions) and developmental stability (a capability for perfect development measured by noise level). It is shown that the change in the noise level, as an expression of the certain entropy level, unlike other forms of phenotypic variability, is a reflection of a change in the system condition. Although the entropy indices of ontogeny and community under certain conditions can change simultaneously, the entropy index at the level of developmental noise proves to be a more unambiguous and universal measure of the disorder of a biological system, compared to biodiversity indices at the community level.

Modeling X chromosome inactivation using t5iLA naive human pluripotent stem cells

BackgroundX chromosome inactivation (XCI) is a critical epigenetic event for dosage compensation of X-linked genes in female mammals, ensuring developmental stability. A robust in vitro model is required for mimicking XCI during the early stages of embryonic development. This methodology article introduces an advanced framework for the in-depth study of XCI using human pluripotent stem cells (hPSCs). By focusing on the transition between naive and primed pluripotent states, we highlight the role of long non-coding RNA X-inactive specific transcript (XIST) and epigenetic alterations in mediating XCI.ResultsOur methodology enables the distinction between naive and primed hESCs based on XIST expression and the activity of X-linked reporters, facilitating the investigation of XCI initiation and maintenance. Through detailed experimental procedures, we demonstrate the utility of our hESC lines in modeling the process of human XCI, including the establishment of conditions for random XCI induction and the analysis of X chromosome reactivation.MethodsThe study outlines a comprehensive approach for characterizing the X chromosome status in hPSCs, employing dual fluorescent reporter hESC lines. These reporter lines enable real-time tracking of XCI dynamics through differentiation processes. We detailed protocols for the induction of X chromosome reactivation and inactivation, as well as the X status characterization methods including cultivation of hESCs, flow cytometric analysis, RNA fluorescence in situ hybridization (FISH), and transcriptome sequencing, providing a step-by-step guide for researchers to investigate XCI mechanisms in vitro.ConclusionsThis article provides a detailed, reproducible methodology for studying XCI mechanisms in vitro, employing hPSCs as a model system. It presents a significant advance in our ability to investigate XCI, offering potential applications in developmental biology, disease modeling, and regenerative medicine. By facilitating the study of XCI dynamics, this methodological framework paves the way for deeper understanding and manipulation of this fundamental biological process.

Rice BARENTSZ genes are required to maintain floral developmental stability against temperature fluctuations.

BARENTSZ (BTZ), a core component of the exon junction complex, regulates diverse developmental processes in animals. However, its evolutionary and developmental roles in plants remain elusive. Here, we revealed that three groups of paralogous BTZ genes existed in Poaceae, and Group 2 underwent loss-of-function mutations during evolution. They showed surprisingly low (~33%) sequence identities, implying functional divergence. Two genes retained in rice, OsBTZ1 and OsBTZ3, were edited; however, the resultant osbtz1 and osbtz3 mutants showed similar floral morphological and functional defects at a low frequency. When growing under low-temperature conditions, developmental abnormalities became pronounced, and new floral variations were induced. In particular, stamen and carpel functionality was impaired in these rice btz mutants. The double-gene mutant osbtz1/3 shared these floral defects with an increased frequency, which was further induced under low-temperature conditions. OsBTZs interacted with OsMADS7 and OsMADS8, and the floral expressions of the OsTGA10 and MADS-box genes were correlatively altered in these osbtz mutants and responded to low-temperature treatment. These novel findings demonstrate that two highly diverged OsBTZs are required to maintain floral developmental stability under low-temperature conditions, and play an integral role in male and female fertility, thus providing new insights into the indispensable roles of BTZ genes in plant development and adaptive evolution.

Urban Life Affects Differentiation and Phenotypic Variation but not Asymmetry in a Fully Terrestrial Salamander

AbstractThe environmental transformations associated with cities are expected to affect organisms at the demographic, phenotypic, and evolutionary level, often negatively. The prompt detection of stressed populations before their viability is compromised is essential to understand species’ responses to novel conditions and to integrate urbanization with biodiversity preservation. The presumably stressful conditions of urban environments are expected to affect organisms’ developmental pathways, resulting in a reduction of the efficacy of developmental stability and canalization processes, which can be observed as increased Fluctuating Asymmetry (FA) and Phenotypic Variance (PV), respectively. Here, we investigated whether patterns of phenotypic variation of urban populations of a fully terrestrial salamander, Salamandra salamandra bernardezi, are affected by urban settings compared to surrounding native forest populations. We sampled populations within and around the city of Oviedo (northern Spain) and used geometric morphometrics to compare morphological differentiation, head shape deviance from the allometric slope, PV, and FA. We also compared morphological patterns with neutral genetic and structure patterns. We observed increased levels of differentiation among urban populations and in PV within certain of them, yet no differences in allometric deviance and FA were detected between habitats, and no morphological measures were found to be correlated with genetic traits. Our results do not support a clear negative impact of urban conditions over salamander populations, but rather suggest that other ecological and evolutionary local processes influence morphological variation in this urban system.

Deciphering the origin of developmental stability: The role of intracellular expression variability in evolutionary conservation.

Progress in evolutionary developmental biology (evo-devo) has deepened our understanding of how intrinsic properties of embryogenesis, along with natural selection and population genetics, shape phenotypic diversity. A focal point of recent empirical and theoretical research is the idea that highly developmentally stable phenotypes are more conserved in evolution. Previously, we demonstrated that in Japanese medaka (Oryzias latipes), embryonic stages and genes with high stability, estimated through whole-embryo RNA-seq, are highly conserved in subsequent generations. However, the precise origin of the stability of gene expression levels evaluated at the whole-embryo level remained unclear. Such stability could be attributed to two distinct sources: stable intracellular expression levels or spatially stable expression patterns. Here we demonstrate that stability observed in whole-embryo RNA-seq can be attributed to stability at the cellular level (low variability in gene expression at the cellular levels). We quantified the intercellular variations in expression levels and spatial gene expression patterns for seven key genes involved in patterning dorsoventral and rostrocaudal regions during early development in medaka. We evaluated intracellular variability by counting transcripts and found its significant correlation with variation observed in whole-embryo RNA-seq data. Conversely, variation in spatial gene expression patterns, assessed through intraindividual left-right asymmetry, showed no correlation. Given the previously reported correlation between stability and conservation of expression levels throughout embryogenesis, our findings suggest a potential general trend: the stability or instability of developmental systems-and the consequent evolutionary diversity-may be primarily anchored in intrinsic fundamental elements such as the variability of intracellular states.

The Behavioral and Productive Characteristics of Japanese Quails (Coturnix japonica) Exposed to Different Monochromatic Lighting

The purpose of this study is to examine the impact of monochromatic illuminations at wavelengths of white (400–700 nm), green (560 nm), yellow (580 nm), blue (480 nm), and red (660 nm) on the performance and behavioral traits of Japanese quails throughout their fattening period. A total of 300 quails in five lighting experimental groups were housed in their conventional rearing cages. Weekly live weights of quails were measured individually, developmental stability was determined, and behavior and fear tests were performed. The body weight averages of quails exposed to blue, green, and yellow light were determined to be greater than those exposed to white and red light (p < 0.05). In terms of the mature weight parameter and the weight of the inflection point of the Gompertz growth model, the averages of the quails exposed to green and blue monochromatic lighting were higher (p < 0.05). The most negative findings on aggressive behavior were observed in birds exposed to monochromatic yellow and red light. Although the body weight of quails exposed to yellow monochromatic lighting was similar to that of quails exposed to green and blue monochromatic lighting, green and blue monochromatic lighting produced the best results in terms of growth, behavior, and developmental stability characteristics. Consequently, it is believed that consistently using green or blue monochromatic lighting programs when raising Japanese quails may provide economic advantages to the producers.

Morphological symmetry of Rhipidomys mastacalis (Mammalia, Rodentia, Cricetidae) in fragmented habitats of the Atlantic Forest in Northeastern Brazil: a study on the influence of the environment on an endemic species

Abstract The Brazilian Atlantic Forest has undergone significant transformation, resulting in habitat loss and the endangerment of many species of mammals and other vertebrates. In this study, the presence of fluctuating asymmetry of four anatomical structures of the arboreal rodent Rhipidomys mastacalis was evaluated using geometric morphometrics. The study focused on adult specimens collected in a mosaic of vegetation composed of forested vegetation, occupancy mosaics in forested areas, and cocoa plantations. The results showed significant values of fluctuating asymmetries in all structures and in all areas. The skulls and scapulae showed the highest values of asymmetry in forested vegetation and cocoa plantations, while the mandibles showed the greatest values in forested vegetation, and the pelvis in occupancy mosaics and cocoa plantations. These findings are consistent with previous studies that have evaluated developmental stability in mammals and suggest that high asymmetry values indicate an effect on different phases of ontogeny, which can harm the survival of a species in future generations. Overall, this study provides important insights into the impacts of habitat fragmentation on Rhipidomys mastacalis and highlights the need for conservation efforts to preserve the integrity of the Brazilian Atlantic Forest and its diverse range of wildlife.

Inner ear morphology in wild versus laboratory house mice.

The semicircular canals of the inner ear are involved in balance and velocity control. Being crucial to ensure efficient mobility, their morphology exhibits an evolutionary conservatism attributed to stabilizing selection. Release of selection in slow-moving animals has been argued to lead to morphological divergence and increased inter-individual variation. In its natural habitat, the house mouse Mus musculus moves in a tridimensional space where efficient balance is required. In contrast, laboratory mice in standard cages are severely restricted in their ability to move, which possibly reduces selection on the inner ear morphology. This effect was tested by comparing four groups of mice: several populations of wild mice trapped in commensal habitats in France; their second-generation laboratory offspring, to assess plastic effects related to breeding conditions; a standard laboratory strain (Swiss) that evolved for many generations in a regime of mobility reduction; and hybrids between wild offspring and Swiss mice. The morphology of the semicircular canals was quantified using a set of 3D landmarks and semi-landmarks analyzed using geometric morphometric protocols. Levels of inter-population, inter-individual (disparity) and intra-individual (asymmetry) variation were compared. All wild mice shared a similar inner ear morphology, in contrast to the important divergence of the Swiss strain. The release of selection in the laboratory strain obviously allowed for an important and rapid drift in the otherwise conserved structure. Shared traits between the inner ear of the lab strain and domestic pigs suggested a common response to mobility reduction in captivity. The lab-bred offspring of wild mice also differed from their wild relatives, suggesting plastic response related to maternal locomotory behavior, since inner ear morphology matures before birth in mammals. The signature observed in lab-bred wild mice and the lab strain was however not congruent, suggesting that plasticity did not participate to the divergence of the laboratory strain. However, contrary to the expectation, wild mice displayed slightly higher levels of inter-individual variation than laboratory mice, possibly due to the higher levels of genetic variance within and among wild populations compared to the lab strain. Differences in fluctuating asymmetry levels were detected, with the laboratory strain occasionally displaying higher asymmetry scores than its wild relatives. This suggests that there may indeed be a release of selection and/or a decrease in developmental stability in the laboratory strain.

Effects of Species-Specific Auditory Stimulation on Broiler Embryos on Hatchability, Developmental Stability, Behavior, and Performance Characteristics

Effects of Species-Specific Auditory Stimulation on Broiler Embryos on Hatchability, Developmental Stability, Behavior, and Performance Characteristics

Facial asymmetry and midsagittal plane definition in 3D: A bias-free, automated method.

Symmetry is a fundamental biological concept in all living organisms. It is related to a variety of physical and social traits ranging from genetic background integrity and developmental stability to the perception of physical appearance. Within this context, the study of human facial asymmetry carries a unique significance. Here, we validated an efficient method to assess 3D facial surface symmetry by best-fit approximating the original surface to its mirrored one. Following this step, the midsagittal plane of the face was automatically defined at the midpoints of the contralateral corresponding vertices of the superimposed models and colour coded distance maps were constructed. The method was tested by two operators using facial models of different surface size. The results show that the midsagittal plane definition was highly reproducible (maximum error < 0.1 mm or°) and remained robust for different extents of the facial surface model. The symmetry assessments were valid (differences between corresponding bilateral measurement areas < 0.1 mm), highly reproducible (error < 0.01 mm), and were modified by the extent of the initial surface model. The present landmark-free, automated method to assess facial asymmetry and define the midsagittal plane of the face is accurate, objective, easily applicable, comprehensible and cost effective.

Effects of the urban environment on the developmental stability, size and body condition of dice snakes (Natrix tessellata) living in artificial lakeside habitats

The expansion of urban areas leads to a decrease in natural habitats, resulting some species to live in urban environments. Novel environmental factors might influence their size, body condition and development stability. The environmentally induced developmental instability can be indicated by fluctuating symmetry, which means random deviations from perfect symmetry in bilaterally symmetric creatures.Our research aimed to explore the impact of various urbanization factors on snake populations within urban habitats. To achieve this, we examined how dice snake (Natrix tessellata) populations differ in their asymmetry, body condition and size in a lake characterized by highly modified lakeside habitats, intensive urban land use, and severe human disturbance. The average size, body condition and two asymmetry indices were determined for 25 dice snake populations around Lake Balaton in Hungary. The impacts of the urban environment were characterized by land use and local variables, and the risk of road kill was also estimated.Populations living in areas with a more intensive road network or near a main road showed more asymmetric traits. It is conceivable that pollutants from vehicle traffic lead to developmental disorders that manifest themselves in more asymmetric individuals. In addition, the body condition of snakes was negatively correlated with the area of the harbours, possibly due to the intensive boat traffic and human disturbance. Finally, populations living in more urbanized areas had larger body sizes meaning that despite its negative effects through pollution, anthropized areas can provide a suitable habitat for dice snakes.While urban artificial surroundings can function as suitable habitats, our results confirm that urban environmental factors have negative effects on dice snakes. Our findings indicate that the density of road networks and the proximity of roads have adverse effects on the developmental stability of urban snakes. This underscores the need to implement conservation actions to mitigate the negative effects of roads on biodiversity.

MADS8 is indispensable for female reproductive development at high ambient temperatures in cereal crops.

Temperature is a major factor that regulates plant growth and phenotypic diversity. To ensure reproductive success at a range of temperatures, plants must maintain developmental stability of their sexual organs when exposed to temperature fluctuations. However, the mechanisms integrating plant floral organ development and temperature responses are largely unknown. Here, we generated barley and rice loss-of-function mutants in the SEPALLATA-like MADS-box gene MADS8. The mutants in both species form multiple carpels that lack ovules at high ambient temperatures. Tissue-specific markers revealed that HvMADS8 is required to maintain floral meristem determinacy and ovule initiation at high temperatures, and transcriptome analyses confirmed that temperature-dependent differentially expressed genes in Hvmads8 mutants predominantly associate with floral organ and meristem regulation. HvMADS8 temperature-responsive activity relies on increased binding to promoters of downstream targets, as revealed by a cleavage under targets and tagmentation (CUT&Tag) analysis. We also demonstrate that HvMADS8 directly binds to 2 orthologs of D-class floral homeotic genes to activate their expression. Overall, our findings revealed a new, conserved role for MADS8 in maintaining pistil number and ovule initiation in cereal crops, extending the known function of plant MADS-box proteins in floral organ regulation.

Developmental Instability and Gene Dysregulation in an Extracted Tetraploid from Hexaploid Wheat.

The BBAA subgenomes of hexaploid common wheat can be 'extracted' to constitute a viable and self-reproducing novel tetraploid wheat, termed extracted tetraploid wheat (ETW). Prior studies have shown ETW manifesting phenotypic abnormalities and alteration in gene expression and epigenetic modifications. No population level investigation has been conducted, leaving the issue unclear regarding whether developmental stability, an essential property evolved in all natural organisms, might have been undermined in ETW. Here, we measured variations in five morphological traits and somatic chromosomal stability in populations of ETW and of its hexaploid donor, a resynthesized hexaploid and a natural tetraploid wheat. We observed phenotypic defects in ETW. Meanwhile, we documented much greater within-population variations in ETW than in the other wheat genotypes, most probably due to disrupted developmental stability in ETW. Also, somatic structural chromosome variations were detected only in ETW. Comparative transcriptome analyses indicated that the disrupted developmental stability of ETW is likely linked to massive dysregulation of genome-wide gene expression rather than to genetic mutations. Population network analysis of gene expression implicated intrinsic connectivity among the variable traits, while gene set enrichment analysis provided possible links between dysregulated gene expression and interlaced trait variation.

Interacting Networks in Social Landscapes: A Devo-Evo Approach to Socialcultural Dynamics

Can the study of epigenetics, physiology, and cognitive science contribute to the investigation and understanding of social-cultural systems while respecting the autonomy of social research? I present a developmental system theory (DST) approach, which takes the unit of analysis to be the system of self-sustaining interactions among multiple biological, psychological, and social resources. On this view, the cybernetic architecture of the networks that constitute the system channels development so that different trajectories lead to convergent end states, accounting for the system’s developmental stability as well as shedding light on the conditions that lead to departures from typical outcomes. Based on previous work, which is extended here, I suggest that Waddington’s epigenetic landscape metaphor, which was built to illustrate the relationship between genetic networks and embryological development, is a useful tool for thinking about the temporal dynamics of social systems, capturing some important features of social stability and change at different scales and levels of social organization. I discuss five social systems using the landscape metaphor and explore the implications of this DST approach for investigating the relations between sociocultural development and evolution.

Fluctuating asymmetry of the Acer negundo L. leaf: an indicator of its state and the quality of the urban environment

The purpose of this study was to analyze the protective function of Acer negundo L. by assessing the indicators of developmental stability by fluctuating leave asymmetry depending on the value of the influence of anthropogenic factors. The materials were obtained from 25 test sites on areas that differed in the degree of road transport impact in 2018–2021 in Irkutsk. The values of the indicators of the developmental stability of each test site were determined as the average of the coefficients of fluctuating asymmetry, considering the eight characteristics of the leaves collected from them. These values indicate that A. negundo is sufficiently resistant to anthropogenic impacts, particularly the effects of emissions from road transport, compared with other types of phanerophytes involved in the landscaping of urbanized areas. The coefficient of weighted average of this indicator between sites in recreational areas and along highways was 1.33. The correlation coefficient between the values of development stability and the distance of growth of A. negundo from highways was r = –0.64±0.18, which confirms the average connection between these characteristics. Analysis of variance was used to assess the stability of tree development in four classes of traffic intensity (high, medium, low, and absent), determined through a correlation ratio, the level of which n = 0.70 demonstrates a high level of connection. To limit the implementation of A. negundo in the local flora, it is recommended that measures be gradually implemented to remove it from parks, squares, gardens, and adjacent territories, with the replacement of woody vegetation species that are well adapted to grow in these habitats.

Developmental Stability, Population Dynamics, and Climate Change, with Particular Reference to the Common Shrew (Sorex areneus L. 1758) in Central Siberia

Developmental Stability, Population Dynamics, and Climate Change, with Particular Reference to the Common Shrew (Sorex areneus L. 1758) in Central Siberia

Relationship between flight muscle dimorphism and wing morphometry in Triatoma infestans (Klug, 1834) (Hemiptera, Reduviidae, Triatominae)

Triatoma infestans, the primary vector of Chagas disease in southern South America, is reported as a dimorphic species for flight muscle development and presents a marked phenotypic plasticity in traits related to flight. In triatomines, studying the relationship between flight muscle development and wing variation is important, since it involves flight capacity and dispersion. Therefore, we examined the association between flight muscle dimorphism and morphological wing variation in T. infestans individuals. We hypothesized that if the underdeveloped flight muscle were associated with a decrease in wing developmental stability, canalization and morphological aspect of wings, and with a loss of wing modularity, then wing variation would be associated with flight muscle dimorphism. Wing size and shape were characterized using geometric morphometrics. Patterns of canalization, developmental instability, and modularity were inferred from fluctuating asymmetry analysis of wing shape. Morphological aspects of wings were estimated using maximum wing length and wing area. The results showed that there are differences in wing shape but not in wing size among groups. Canalization and developmental stability were positively associated in individuals with muscle development and negatively associated in individuals with underdeveloped flight muscles. The covariance structure of variation among individuals was different between groups but not for fluctuating asymmetry, both for females and males. Modularity hypothesis related to the wing subdivision into two parts, a stiff part and a membranous one, showed significant association for the variation among individuals and fluctuating asymmetry variation in females with flight muscles. Wing aspect showed that females with flight muscles exhibited more elongated and thinner wings than those without flight muscles. The results obtained in this study reveal an association between flight muscle development and forewing variation in T. infestans. Females with flight muscles have certain differential characteristics in their wings that would be related to an enhanced flight performance.

Effect of four plant extracts on the mortality, population growth, and fluctuating asymmetry of Sitophilus oryzae

AbstractManagement of storage pest insects relies heavily on chemical control, and there is a need to develop more sustainable management practices. Here, we evaluated the impact of 2% ethanol plant extracts of Ajuga reptans L., Ajuga pyramidalis L. (both Lamiaceae), Urtica dioica L. (Urticaceae), and Cannabis sativa L. (Cannabaceae) plants on mortality, population growth, and developmental stability [measuring fluctuating asymmetry (FA)] of the rice weevil, Sitophilus oryzae (L.) (Coleoptera: Curculionidae), a worldwide stored product pest. FA refers to small, random deviations occurring between the left and right sides of bilaterally symmetrical organisms; these deviations increase in response to environmental stress, making FA a reliable method to measure the impact of stress. FA was measured by means of geometric morphometrics, a method that allows for analyzing the whole landmark configuration of the insect, rather than taking single measurements. Extracts of the mentioned plants were used to treat maize (Zea mays L., Poaceae) kernels on which experimental populations of the rice weevil were grown, and we assessed mortality after 24–72 h, population growth after 30–90 days, and developmental stability after 90 days. Screening bioassays showed that S. oryzae adults were most affected by Ajuga extracts; Ajuga spp., especially A. reptans, significantly reduced population growth. In concordance, Ajuga extracts increased FA. The effects of U. dioica and C. sativa extract were less pronounced. None of the extracts significantly affected insect mortality. Overall, it can be concluded that A. reptans and A. pyramidalis are potential sources of bioactive compounds that may be further used for S. oryzae control. The results obtained confirm that variation in body shape asymmetry can be used as an indicator of population disturbance when insects are exposed to different types of stressors.

Self-Organization and Genomic Causality in Models of Morphogenesis.

The debate about what causes the generation of form and structure in embryological development goes back to antiquity. Most recently, it has focused on the divergent views as to whether the generation of patterns and form in development is a largely self-organized process or is mainly determined by the genome, in particular, complex developmental gene regulatory processes. This paper presents and analyzes pertinent models of pattern formation and form generation in a developing organism in the past and the present, with a special emphasis on Alan Turing's 1952 reaction-diffusion model. I first draw attention to the fact that Turing's paper remained, at first, without a noticeable impact on the community of biologists because purely physical-chemical models were unable to explain embryological development and often also simple repetitive patterns. I then show that from the year 2000 and onwards, Turing's 1952 paper was increasingly cited also by biologists. The model was updated to include gene products and now seemed able to account for the generation of biological patterns, though discrepancies between models and biological reality remained. I then point out Eric Davidson's successful theory of early embryogenesis based on gene-regulatory network analysis and its mathematical modeling that not only was able to provide a mechanistic and causal explanation for gene regulatory events controlling developmental cell fate specification but, unlike reaction-diffusion models, also addressed the effects of evolution and organisms' longstanding developmental and species stability. The paper concludes with an outlook on further developments of the gene regulatory network model.