Unit responses of the medial group of thalamic nuclei to stimulation of the frontobasal regions of the neocortex

In acute experiments on cats anesthetized with pentobarbital and chloralose, single-unit and focal responses of the medial group of thalamic nuclei (mediodorsal, central lateral, paracentral, central medianum, parafascicular) were studied to stimulation of the frontobasal regions of the cortex (proreal, posterior orbital, basal temporal regions). Depending on the number of neurons responding to cortical stimulation and on the length of the latent period of the responses three functionally heterogeneous subdividions of the medial nuclei were distinguished; the parvocellular and magnocellular portions of the mediodorsal nucleus and the intralaminar nuclei with the parafascicular complex. On the basis of responses of neurons activated antidromically by stimulation of the same cortical region and synaptically by stimulation of another region, the concept of the integrative function of nuclei of the medial group, integrating the frontobasal zones of the neocortex with the aid of neuron circuits in which the medial nuclei are included, is argued.M. Gor'kii Donetsk Medical Institute. Translated from Neirofiziologiya, Vol. 9, No. 1, pp. 11–18, January–February, 1977.     

Field homology: a meaningful definition

Field homology refers to populations of cells that derive from evolutionarily conserved regions of embryos but are distributed across sets of adult morphological structures that cannot be placed in one-to-one correspondance. The concept of field homology has proven especially attractive to comparative neurologists because it allows them to deal with the fact that sets of nuclei or nuclear subdivisions often cannot be compared on a one-to-one basis across phyletic groups. However, the concept of field homology has recently come under criticism. It has been argued that field homology is theoretically impossible because it requires sequences of developmental stages to be both evolutionarily conserved and evolutionarily modified. It has also been argued that field homology allows overly vague comparisons of adult morphological structures, fails to account for homologous structures that derive from non-homologous embryonic sources, and establishes overly rigid links between embryonic and adult morphology. All of these criticisms may be adequately addressed by explaining field homology in terms of differentiation. The present paper explains field homology in terms of differentiation using the amniote dorsal thalamus to illustrate major points. It is concluded that field homology is a meaningful concept when defined in terms of differentiation, applied to appropriate cases, and properly limited in its comparisons of adult structures.     

Effect of Structure on Function in Model Nerve Nets

A theoretical analysis has been made on the effect of the pattern of interneuronal connectivity in model nerve nets on the activity of these nets. Two types of nets have been investigated: one in which the likelihood of a connection between a given neuron and any other element in the net is given by a Poisson probability distribution, and a second type in which the pattern of interconnection follows a Gaussian distribution. An analytical treatment is presented of the equations for noiseless nets in these two conditions. The principal result is that nets with Poisson connectivity law are activated by extraneous firing of a single neuron and continue in spontaneous activity indefinitely. On the other hand, similar nets in which the connections are, however, distributed according to a normal connectivity law, exhibit a definite threshold and produce spontaneous activity only subsequent to extraneous activation of a substantial fraction of the population. Moreover, spontaneous activity in Gaussian nets, but not in Poisson nets, becomes extinguished if the number of active neurons falls below the critical threshold. Some neuroanatomical implications are discussed which suggest that the pyramidal system of the cerebral cortex and other neuronal systems histologically characterized by large numbers of synapses per neuron may incorporate a Gaussian connectivity law, whereas a Poisson law may be characteristic of these cortical layers and nuclei primarily containing granule cells.     

Contemporary concepts of homology in biology (a theoretical review)

A brief review of the contemporary theoretical concepts of homology being developed basically in systematics and phylogenetics as well as in developmental biology is presented. Ontologically, both homology and analogy represent a kind of correspondence considered from the standpoint of nominalism, realism, and conceptualism. According to their nominalistic treatment, both are described by a set-theory approximation which makes them classes (in the logical sense). The realistic treatment provides their holistic view according to which a homologue is an anatomical or evolutionary singular while analogue remains a class. The conceptualistic treatment means that there are real (objective) correspondences existing among real (objective) entities while fixation of any of them is based on certain theoretical presumptions adopted by a researcher; homology as a natural kind (including homeostatic property cluster) seems to be most consistent with such a treatment. Realistic view of homology makes it "absolute", while two others make discrimination of homology and analogy strictly relative. Two basic general homology concepts have been developed in recent literature--taxic and transformational ones; the first considers respective correspondences as structure relations, the second as process relations. The taxic homology is nearly the same as classical typological one (Owen), while transformational homology unites all its phylogenetic, ontogenetic (developmental) and transformation-typological definitions. Process-structuralistic approach seems to unite both taxic and transformational ones. The latter makes it possible to apply general homology concept not only to structures but to processes as well. It is stressed that homology is not identical to the similarity, the latter being just the means for revealing the former. Some closer consideration is given to phylogenetic, ontogenetic and genetic treatments of homology; significant uncertainty is shown to exist between them which causes the "homology problem". Epistemologically, any homology statement has a status of hypothesis which makes such a statement theory-dependent according to the hypothetic-deductive argumentation scheme. This dependence allows to stress once more the relative nature of homology and analogy correspondences. Some questions concerning operational concepts and criteria of homology are considered. A hierarchical concept of homology seems to be the most promising prospect of future development of the "homology problem".     

Reconstructing serial homology with a special emphasis on the nature of limbs in vertebrates and with references to Cruveilhier,Wyman, Belogolowy,and Balinsky

This analysis was inspired by the recent paper by Siomava et al. (2020) who attempted to deconstruct the serial homology concept, but retain the special homology. The criticism against this attempt is presented based on reconsideration of the original Owen's trinitarian concept of the general, serial, and special homology, and on a number of evidence on the vertebrate limbs serial homologies and on the vertebrate occiput special homologies which are currently missed by the morphologist community. The research of Belogolowy (1911) proved that the concept of special homology can be deconstructed with the same reasoning as suggested by Siomava et al. (2020) against the serial homology concept. It is argued that the deconstruction attempts come from wrong expectations in respect of homology. It is argued, that, due to developmental singularities, such as the zygote, or spore, or bud (in vegetative reproduction), the true homogeny is possible for genes only. The organs do not arise from organs, and therefore their genetic basis, and hence homology, can be changed in the developmental singularities. Thus, the morphological homology is not static. It can be acquired and it can evolve. Genetically, the evolution of morphological homologies can be thought of as a succession of co-options. The evidence for a succession of serial homologies in vertebrate limbs is suggested. It is argued that homology and analogy have a sense only in relation to each other. When two correspondences between two organs exist simultaneously, the older (deeper in time) is homology, and the newer (more superficial) is analogy. In this conceptual framework of evolvable homology, neither of the three Owen's types of homology can be abandoned. Three respective types of analogy should be added—the general analogy, the serial analogy, and the special analogy.     

The multiple facets of homology and their use in comparative genomics to study the evolution of genes, genomes, and species

The incredible development of comparative genomics during the last decade has required a correct use of the concept of homology that was previously utilized only by evolutionary biologists. Unhappily, this concept has been often misunderstood and thus misused when exploited outside its evolutionary context. This review brings back to the correct definition of homology and explains how this definition has been progressively refined in order to adapt it to the various new kinds of analysis of gene properties and of their products that appear with the progress of comparative genomics. Then, we illustrate the power and the proficiency of such a concept when using the available genomics data in order to study the evolution of individual genes, of entire genomes and of species, respectively. After explaining how we detect homologues by an exhaustive comparison of a hundred of complete proteomes, we describe three main lines of research we have developed in the recent years. The first one exploits synteny and gene context data to better understand the mechanisms of genome evolution in prokaryotes. The second one is based on phylogenomics approaches to reconstruct the tree of life. The last one is devoted to reminding that protein homology is often limited to structural segments (SOH=segment of homology or module). Detecting and numbering modules allows tracing back protein history by identifying the events of gene duplication and gene fusion. We insist that one of the main present difficulties in such studies is a lack of a reliable method to identify genuine orthologues. Finally, we show how these homology studies are helpful to annotate genes and genomes and to study the complexity of the relationships between sequence and function of a gene.     

Thoughts on the development, structure and evolution of the mammalian and avian telencephalic pallium

Various lines of evidence suggest that the development and evolution of the mammalian isocortex cannot be easily explained without an understanding of correlative changes in surrounding areas of the telencephalic pallium and subpallium. These are close neighbours in a common morphogenetic field and are postulated as sources of some cortical neuron types (and even of whole cortical areas). There is equal need to explain relevant developmental evolutionary changes in the dorsal thalamus, the major source of afferent inputs to the telencephalon (to both the pallium and subpallium). The mammalian isocortex evolved within an initially small dorsal part of the pallium of vertebrates, surrounded by other pallial parts, including some with a non-cortical, nuclear structure. Nuclear pallial elements are markedly voluminous in reptiles and birds, where they build the dorsal ventricular ridge, or hypopallium, which has been recently divided molecularly and structurally into a lateral pallium and a ventral pallium. Afferent pallial connections are often simplified as consisting of thalamic fibres that project either to focal cell aggregates in the ventral pallium (predominant in reptiles and birds) or to corticoid areas in the dorsal pallium (predominant in mammals). Karten's hypothesis, put forward in 1969, on the formation of some isocortical areas postulates an embryonic translocation into the nascent isocortex of the ventropallial thalamorecipient foci and respective downstream ventropallial target populations, as specific layer IV, layers II- III, or layers V-VI neuron populations. This view is considered critically in the light of various recent data, contrasting with the alternative possibility of a parallel, separate evolution of the different pallial parts. The new scenario reveals as well a separately evolving tiered structure of the dorsal thalamus, some of whose parts receive input from midbrain sensory centres (collothalamic nuclei), whereas other parts receive oligosynaptic 'lemniscal' connections bypassing the midbrain (lemnothalamic nuclei). An ampler look into known hodological patterns from this viewpoint suggests that ancient collothalamic pathways, which target ventropallial foci, are largely conserved in mammals, while some emergent cortical connections can be established by means of new collaterals in some of these pathways. The lemnothalamic pathways, which typically target ancestrally the dorsopallial isocortex, show parallel increments of relative size and structural diversification of both the thalamic cell populations and the cortical recipient areas. The evolving lemnothalamic pathways may interact developmentally with collothalamic corticopetal collaterals in the modality-specific invasion of the emergent new areas of isocortex.     

Agonist-induced PIP(2) hydrolysis inhibits cortical actin dynamics: regulation at a global but not at a micrometer scale

Phosphatidylinositol 4, 5-bisphosphate (PIP(2)) at the inner leaflet of the plasma membrane has been proposed to locally regulate the actin cytoskeleton. Indeed, recent studies that use GFP-tagged pleckstrin homology domains (GFP-PH) as fluorescent PIP(2) sensors suggest that this lipid is enriched in membrane microdomains. Here we report that this concept needs revision. Using three distinct fluorescent GFP-tagged pleckstrin homology domains, we show that highly mobile GFP-PH patches colocalize perfectly with various lipophilic membrane dyes and, hence, represent increased lipid content rather than PIP(2)-enriched microdomains. We show that bright patches are caused by submicroscopical folds and ruffles in the membrane that can be directly visualized at approximately 15 nm axial resolution with a novel numerically enhanced imaging method. F-actin motility is inhibited significantly by agonist-induced PIP(2) breakdown, and it resumes as soon as PIP(2) levels are back to normal. Thus, our data support a role for PIP(2) in the regulation of cortical actin, but they challenge a model in which spatial differences in PIP(2) regulation of the cytoskeleton exist at a micrometer scale.     

Acrolein, a product of lipid peroxidation, inhibits glucose and glutamate uptake in primary neuronal cultures

Oxidative stress has been implicated in the pathogenesis of several neurodegenerative disorders including Alzheimer's disease (AD). Increased lipid peroxidation, decreased levels of polyunsaturated fatty acids, and increased levels of 4-hydroxynonenal (HNE), F(2)-isoprostanes, and F(4)-neuroprostanes are present in the brain in patients with AD. Acrolein, an alpha,beta-unsaturated aldehydic product of lipid peroxidation has been demonstrated to be approximately 100 times more reactive than HNE and is present in neurofibrillary tangles in the brain in AD. We recently demonstrated statistically significant elevated concentrations of extractable acrolein in the hippocampus/parahippocampal gyrus and amygdala in AD compared with age-matched control subjects. Concentrations of acrolein were two to five times those of HNE in the same samples. Treatment of hippocampal cultures with acrolein led to a time- and concentration-dependent decrease in cell survival as well as a concentration-dependent increase in intracellular calcium. In cortical neuron cultures, we now report that acrolein causes a concentration-dependent impairment of glutamate uptake and glucose transport in cortical neuron cultures. Treatment of cortical astrocyte cultures with acrolein led to the same pattern of impairment of glutamate uptake as observed in cortical neuron cultures. Collectively, these data demonstrate neurotoxicity mechanisms of arolein that might be important in the pathogenesis of neuron degeneration in AD.     

Fiber Pathway Pathology,Synapse Loss and Decline of Cortical Function in Schizophrenia

A quantitative cortical model is developed, based on both computational and simulation approaches, which relates measured changes in cortical activity of gray matter with changes in the integrity of longitudinal fiber pathways. The model consists of modules of up to 5,000 neurons each, 80% excitatory and 20% inhibitory, with these having different degrees of synaptic connectiveness both within a module as well as between modules. It is shown that if the inter-modular synaptic connections are reduced to zero while maintaining the intra-modular synaptic connections constant, then activity in the modules is reduced by about 50%. This agrees with experimental observations in which cortical electrical activity in a region of interest, measured using the rate of oxidative glucose metabolism (CMR_glc(ox)), is reduced by about 50% when the cortical region is isolated, either by surgical means or by transient cold block. There is also a 50% decrease in measured cortical activity following inactivation of the nucleus of Meynert and the intra-laminar nuclei of the thalamus, which arise either following appropriate lesions or in sleep. This occurs in the model if the inter-modular synaptic connections require input from these nuclei in order to function. In schizophrenia there is a 24% decrease in functional anisotropy of longitudinal fasciculi accompanied by a 7% decrease in cortical activity (CMR_glc(ox)).The cortical model predicts this, namely for a 24% decrease in the functioning of the inter-modular connections, either through the complete loss of 24% of axons subserving the connections or due to such a decrease in the efficacy of all the inter-modular connections, there will be about a 7% decrease in the activity of the modules. This work suggests that deterioration of longitudinal fasciculi in schizophrenia explains the loss of activity in the gray matter.     

Multisynaptic activity in a pyramidal neuron model and neural code

The highly irregular firing of mammalian cortical pyramidal neurons is one of the most striking observation of the brain activity. This result affects greatly the discussion on the neural code, i.e. how the brain codes information transmitted along the different cortical stages. In fact it seems to be in favor of one of the two main hypotheses about this issue, named the rate code. But the supporters of the contrasting hypothesis, the temporal code, consider this evidence inconclusive. We discuss here a leaky integrate-and-fire model of a hippocampal pyramidal neuron intended to be biologically sound to investigate the genesis of the irregular pyramidal firing and to give useful information about the coding problem. To this aim, the complete set of excitatory and inhibitory synapses impinging on such a neuron has been taken into account. The firing activity of the neuron model has been studied by computer simulation both in basic conditions and allowing brief periods of over-stimulation in specific regions of its synaptic constellation. Our results show neuronal firing conditions similar to those observed in experimental investigations on pyramidal cortical neurons. In particular, the variation coefficient (CV) computed from the inter-spike intervals (ISIs) in our simulations for basic conditions is close to the unity as that computed from experimental data. Our simulation shows also different behaviors in firing sequences for different frequencies of stimulation.     

Morphometric characteristics of neuron-glial relations in brain edema caused by stimulation of hypothalamic nuclei

Morphologic characteristics and certain changes in cell composition of the cortex and the white substance of the brain have been studied at experimentally produced brain edema by stimulation of the lateral hypothalamic field, the indefinite zone, Forel's fields H1 and H2. It has been stated that diffuse edema of the white substance and perivascular edema dominate in histopathological changes. Morphometrical analysis of the structural changes had demonstrated a certain increase in the cortex thickness, decreased density in the arrangement of the neurons and increased volume of their nuclei at more moderate enlargement of their body volumes, as well as increased volume of the nuclei in the cortical glial cells and the white substance cells. In the cortex cells is observed, that is accompanied with increased glial index and average number of perineuronal gliocytes per one neuron. Simultaneously, in both hemispheres, the character in the arrangement of the perineuronal glia as regards the neuron changes. At the same time, in the white substance, the density of the glial arrangement sharply decreases. The changes have demonstrated that wider perivascular spaces predominate in small vessels. All the changes mentioned are more pronounced in the contralateral hemisphere.     

Homology: a synthetic concept of evolutionary robustness of patterns

The history of the homology concept is a history of attempts to conceive the basis of sameness in biology. Since it was formulated in the middle of the 19th century, the concept has had to fit an ever growing number of scientific fields and purposes. These different demands have resulted in diverging, sometimes, incompatible definitions. The inconsistencies are mostly due to the lack of a clear separation of hypotheses of maintenance from hypotheses of transformation. A synthetic approach to define homology thus has to consider the following pivotal points: (i) hypotheses of evolutionary maintenance should be kept separate from hypotheses of evolutionary transformation; (ii) the definition of homology should provide the foundation for exact specifications of what is hypothesised to be homologous and (iii) restrictions to particular levels of observation or specific scientific purposes, and the exclusion of iterative homology should be avoided. We suggest that patterns should be delineated by characterizing components of traits, and by describing connections and interactions between these components. A shared pattern of compared traits where the characterization shows 1 : 1 correspondence may then be homologised. Homology is equivalent to a hypothesis that the pattern, starting from a single starting point, was transmitted robustly along diverging branches of a genealogical tree, that is, the homologised pattern was never changed by any transformation. The proposed definition of homology is thus, ‘A pattern corresponding in a set of compared traits is homologous, if after a common evolutionary origin, the pattern was maintained along diverging lineages by robust pattern transmission’. After justifying the terminological use in our definition, we discuss the interplay of our definition with the pivotal points mentioned above in comparison to other definitions. Since our homology definition is a concept of pattern maintenance, it is clearly demarcated from transformation hypotheses, which are covered by the character concept. Robustness is understood as evolutionary maintenance of correspondence in objects linked by genealogical relations. The characterization of the pattern suffices to provide the necessary conditional phrase by specifying what is hypothesised to be homologous. Allowing development to be conceptualised as a pattern formation process makes it easier to deal with traits that are transmitted indirectly to the next generation. Patterns can be characterized on all observational levels, but the components and the quality of connections and interactions used for the characterization may differ. The replacement of the reference to an ancestor–descendant relationship by a reference to robust pattern transmission allows for the inclusion of iterative homology into the concept. In the final part of the paper, detailed reformulations of the ‘criteria’ for the corroboration of homology hypotheses as proposed by Remane (1952 ) are given.     

Quantitative study of cellular and volumetric growth of magnocellular and laminar auditory nuclei in developing chick brainstem

Development of the second and third order auditory nuclei—nucleus magnoscellularis (NM) and nucleus laminaris (NL) respectively—was studied using Nissl stained serial sections from brain specimens between 8 day of incubation and posthatch day 1, at every two day interval. Reconstruction of these nuclei from three incubation ages showed progressive growth of both nuclei in a rostrocaudal direction. The volume, total neuron, dead cell and glial cell numbers were estimated using stereological quantitation methods. Both nuclei, while undergoing an overall gradual increase in volume up to 20 days registered a transient drop in volume; earlier for NM at 10 days and later for NL at 18 days. From day 20 the two nuclei showed accelerated growth in volume. The total neuron count rapidly declined up to 12 days with 43% loss of neurons in NM followed by a rise and later stabilization within a certain range. The NL, however, showed a continuous fall in neuron numbers throughout the incubation period with 20% cell loss by day 12 and an overall loss of 52%. Cell death in both nuclei was maximal at 16 days and spanned the entire period of incubation. Glia showed a biphasic increase with peak at 14 days for both NM and NL followed by a subsequent rise at day 20 for both nuclei. These data would help in planning further experimental studies of auditory manipulation.     

Microstructure of the neocortex: Comparative aspects

The appearance of the neocortex, its expansion, and its differentiation in mammals, represents one of the principal episodes in the evolution of the vertebrate brain. One of the fundamental questions in neuroscience is what is special about the neocortex of humans and how does it differ from that of other species? It is clear that distinct cortical areas show important differences within both the same and different species, and this has led to some researchers emphasizing the similarities whereas others focus on the differences. In general, despite of the large number of different elements that contribute to neocortical circuits, it is thought that neocortical neurons are organized into multiple, small repeating microcircuits, based around pyramidal cells and their input-output connections. These inputs originate from extrinsic afferent systems, excitatory glutamatergic spiny cells (which include other pyramidal cells and spiny stellate cells), and inhibitory GABAergic interneurons. The problem is that the neuronal elements that make up the basic microcircuit are differentiated into subtypes, some of which are lacking or highly modified in different cortical areas or species. Furthermore, the number of neurons contained in a discrete vertical cylinder of cortical tissue varies across species. Additionally, it has been shown that the neuropil in different cortical areas of the human, rat and mouse has a characteristic layer specific synaptology. These variations most likely reflect functional differences in the specific cortical circuits. The laminar specific similarities between cortical areas and between species, with respect to the percentage, length and density of excitatory and inhibitory synapses, and to the number of synapses per neuron, might be considered as the basic cortical building bricks. In turn, the differences probably indicate the evolutionary adaptation of excitatory and inhibitory circuits to particular functions.     

Independent parcellation of the embryonic visual cortex and thalamus revealed by combinatorial Eph/ephrin gene expression

The visual cortex in primates is parcellated into cytoarchitectonically, physiologically, and connectionally distinct areas: the striate cortex (V1) and the extrastriate cortex, consisting of V2 and numerous higher association areas [1]. The innervation of distinct visual cortical areas by the thalamus is especially segregated in primates, such that the lateral geniculate (LG) nucleus specifically innervates striate cortex, whereas pulvinar projections are confined to extrastriate cortex [2--8]. The molecular bases for the parcellation of the visual cortex and thalamus, as well as the establishment of reciprocal connections between distinct compartments within these two structures, are largely unknown. Here, we show that prospective visual cortical areas and corresponding thalamic nuclei in the embryonic rhesus monkey (Macaca mulatta) can be defined by combinatorial expression of genes encoding Eph receptor tyrosine kinases and their ligands, the ephrins, prior to obvious cytoarchitectonic differentiation within the cortical plate and before the establishment of reciprocal connections between the cortical plate and thalamus. These results indicate that molecular patterns of presumptive visual compartments in both the cortex and thalamus can form independently of one another and suggest a role for EphA family members in both compartment formation and axon guidance within the visual thalamocortical system.     

Nup93, a Vertebrate Homologue of Yeast Nic96p, Forms a Complex with a Novel 205-kDa Protein and Is Required for Correct Nuclear Pore Assembly

Yeast and vertebrate nuclear pores display significant morphological similarity by electron microscopy, but sequence similarity between the respective proteins has been more difficult to observe. Herein we have identified a vertebrate nucleoporin, Nup93, in both human and Xenopus that has proved to be an evolutionarily related homologue of the yeast nucleoporin Nic96p. Polyclonal antiserum to human Nup93 detects corresponding proteins in human, rat, and Xenopus cells. Immunofluorescence and immunoelectron microscopy localize vertebrate Nup93 at the nuclear basket and at or near the nuclear entry to the gated channel of the pore. Immunoprecipitation from both mammalian and Xenopus cell extracts indicates that a small fraction of Nup93 physically interacts with the nucleoporin p62, just as yeast Nic96p interacts with the yeast p62 homologue. However, a large fraction of vertebrate Nup93 is extracted from pores and is also present in Xenopus egg extracts in complex with a newly discovered 205-kDa protein. Mass spectrometric sequencing of the human 205-kDa protein reveals that this protein is encoded by an open reading frame, KIAAO225, present in the human database. The putative human nucleoporin of 205 kDa has related sequence homologues in Caenorhabditis elegans and Saccharomyces cerevisiae. To analyze the role of the Nup93 complex in the pore, nuclei were assembled that lack the Nup93 complex after immunodepletion of a Xenopus nuclear reconstitution extract. The Nup93-complex–depleted nuclei are clearly defective for correct nuclear pore assembly. From these experiments, we conclude that the vertebrate and yeast pore have significant homology in their functionally important cores and that, with the identification of Nup93 and the 205-kDa protein, we have extended the knowledge of the nearest-neighbor interactions of this core in both yeast and vertebrates.     

Phylogeny and evo-devo: characters, homology, and the historical analysis of the evolution of development

The concept of homology continues to attract more and more commentary. In systematic and evolutionary biology the meaning of homology as synapomorphic similarity inherited from a common ancestor has gained wide acceptance over the last three or four decades. In recent years, however, developmental biologists, in particular, have argued for a new approach to, and new definition for, homology that revolves around the desire to make it more process-oriented and more mechanistic. These efforts raise questions about the relationship between developmental and evolutionary biology as well as how the evolution of development is to be studied. It is argued in this paper that this new approach to homology seemingly decouples developmental biology from the study of the evolution of development rather than to facilitate that study. In contrast, applying the notion of historical, phylogenetic homology to developmental data is inherently comparative and therefore evolutionary.