Wilhelm His Research Articles

Friedrich Miesher’s life path and contribution to science

The article discusses the main stages of life and activity of the famous Swiss organic chemist, Friedrich Miescher (August 13, 1844 – August 26, 1895), who was the first to isolate and describe the structure of the DNA molecule. F. Miescher was born in a family of scientists and doctors, studied medicine at the University of Basel (Switzerland), but did not become a practicing doctor. He mostly conducted his scientific research in the biochemical laboratory of Felix Hoppe-Zeyler in Tübingen (Germany). The object of the scientist's research was leukocytes, from the nuclei of which he managed to isolate a precipitate insoluble in most of the solvents known at that time. In 1869, F. Miescher obtained a molecule that he named nuclein (DNA). In the course of research, the scientist established its composition, some properties, and molecular weight, but was unable to describe its functions. Subsequently, F. Miescher discovered the presence of nucleic in the cells of other tissues, in the spermatozoa of many species of animals. At the Institute of Physiology of the University of Leipzig (Germany) in the laboratory of Karl Ludwig Friedrich Miescher studied the nerve pathways that transmit pain signals in the spinal cord. In 1871, the scientist completed his habilitation for the position of a professor at Basel University; he chose physiology of breathing as the topic of his work. F. Mischer continued to study the features of spermatozoa and oocytes; developed a number of theories regarding understanding of the processes of fertilization and transmission of hereditary traits, which, due to the lack of knowledge at the time, were quite speculative. In 1885, the scientist founded and headed the first in Switzerland Institute of Anatomy and Physiology in Vesalian, where he worked for 10 years. Friedrich Miescher died at the age of 52, before the results of his discovery were recognized. Only in 1944 it was proved that the DNA molecule is the carrier of genetic information. Most of the results of F. Miescher's scientific work were published after his death by his uncle, the famous Swiss anatomist Wilhelm His.

What's Old is New Again - The Anatomical Studies of Franklin P. Mall and the Fascial-Interstitial Spaces.

Franklin Mall was one of the foremost scientists of the turn of the 19th century, an exemplary mentor as well as researcher, and his revolutionary contributions are still relevant today. Mall's early training in Leipzig with Wilhelm His and Carl Ludwig provided him with an unusual perspective on the integration of anatomy and physiology, and his interest in the links between structure and function guided the work he carried out after joining the faculty of the new Johns Hopkins University School of Medicine. Mall carried out innovative studies on the one hand using dye injection to trace blood and lymphatic supplies to different organs and on the other hand using "putrefaction" to digest tissues and study the organization of the reticular space, demonstrating that it was the underlying source of support for all the organs. These two studies of Mall's, carried out independently, provide the basis for modern studies integrating the understanding of fascia and interstitial spaces. This article is protected by copyright. All rights reserved.

Molecular mechanisms governing development of the hindbrain choroid plexus and auditory projection: A validation of the seminal observations of Wilhelm His.

Studies by His from 1868 to 1904 delineated the critical role of the dorsal roof plate in the development of the hindbrain choroid plexus, and of the rhombic lips in the development of hindbrain auditory centers. Modern molecular studies have confirmed these observations and placed them in a mechanistic context. Expression of the transcription factor Lmx1a/b is crucial to the development of the hindbrain choroid plexus, and also regulates the expression of Atoh1, a transcription factor that is essential for the formation of the cochlear hair cells and auditory nuclei. By contrast, development of the vestibular hair cells, vestibular ganglion and vestibular nuclei does not depend on Lmx1a/b. These findings demonstrate a common dependence on a specific gene for the hindbrain choroid plexus and the primary auditory projection from hair cells to sensory neurons to hindbrain nuclei. Thus, His’ conclusions regarding the origins of specific hindbrain structures are borne out by molecular genetic experiments conducted more than a hundred years later.

Developmental Twists: The Attic.

The first days with my parents were my happiest. Every morning my mother would plant three kisses on my forehead before taking me in her arms. “She's got your mouth dear,” she'd say to my father as she carried me over to him. “Wait, she's moving!” She'd take my father's hand and place it on her belly to feel the muted kicks of the one who would soon depose me.That was 31 years ago. I live in an attic now, and spend most time researching into my ancestry. So far, I've traced my forebears back to 1852, when the German-born embryologist Adolf Ziegler (1820-1889) carved frogs journeying from fertilised egg to swimming tadpole. Then, as microtomes became all the rage in the 1860s, the Swiss anatomist Wilhelm His, Sr (1831-1904) began slicing his way through embryos. He advocated a mechanical view of development, with tissues bending and folding through differential growth. Based on his drawings, Ziegler sculpted the chick's voyage, with cutaways showing colour-coded vessels and organs as they formed.Things took a slightly ghoulish turn in the 1870s when Wilhelm His fed his microtomes with humans, garnered from abortions, miscarriages, post-mortems and anatomical museums. Adolf Ziegler's health was failing, so it was his son, Friedrich, who carved the colour atlas, marching from a few weeks post-conception towards foetal glory.Then, Gustav Jacob Born (1851-1900) entered the scene. Whereas Wilhelm His had relied on freehand drawings, Born – a German histologist – traced outlines of serial sections and stacked them up to reconstruct the whole. The two methods came head-to-head at the first meeting of German Anatomical Society in Leipzig in 1887. Born won.The heyday of my forebears had arrived. As cubism, relativity, quantum mechanics and genetics stepped onto the world stage, Friedrich Ziegler's studio shaped, replicated and disseminated its creations. The waxen forms permeated embryological research, anatomical institutes, gynaecological clinics, public museums.But as experimental embryology came into fashion, interest in models and mechanics waned. By the 1960s, most of my ancestors had been either been melted down, or relegated to glass cases, exhumed only for the edification of medical students. With the surge in developmental genetics in the 1980s, oblivion seemed assured.Yet the abandoned dust-tracks of one generation can become fashionable avenues for the next. As cells and gene products started to be visualised, first in sections, then in volumes and finally through live imaging, Born's serial reconstruction methods resurfaced to produce movies of rotating fluorescent bodies and 3D prints. Developmental mechanics returned in a computational guise to explain shape changes through the action of physical forces based on cellular dynamics.It was around then that my parents saw the advert: “Get to know your baby ahead of time. Hold her in your hands, see who she looks like. Gold-plating available.” Within two days of the ultrasound scan, I was in my mother's arms.I was as excited as my parents to welcome my template home. As I watched her wriggle, grasp and suckle, she seemed my avatar, expressing through bodily movements what I could only wish for. The next morning, I waited in vain for morning kisses, only to see them being showered on the new arrival. Didn't take long before I was relegated to a box in the attic, like my ancestors dispatched to their glass tombs.Yet, though the cause of my banishment, she is still my nearest relative. What does she look like now? What career did she follow? Will she one day lift the lid to rediscover her earliest snapshot? Hush, I think I hear footsteps. Read other ‘Developmental Twists’ articles by Tsuku MogamiMogami, T. (2021). Developmental Twists: The Scan. Development148, dev200108. doi:10.1242/dev.200108Mogami, T. (2021). Developmental Twists: Only Human. Development148, dev200204. doi:10.1242/dev.200204Mogami, T. (2021). Developmental Twists: Back to Back. Development148, dev200268. doi:10.1242/dev.200268Mogami, T. (2021). Developmental Twists: A Colourful Character. Development148, dev200360. doi:10.1242/dev.200360Mogami, T. (2022). Developmental Twists: A Fateful Tour. Development149, dev200453. doi:10.1242/dev.200453Mogami, T. (2022). Developmental Twists: A Fertile Encounter. Development149, dev200523. doi:10.1242/dev.200523Mogami, T. (2022). Developmental Twists: Winter in Paris. Development149, dev200658. doi:10.1242/dev.200658Mogami, T. (2022). Developmental Twists: Sorgvliet. Development149, dev200847. doi:10.1242/dev.200847

Regulation of early cerebellar development.

The study of cerebellar development has been at the forefront of neuroscience since the pioneering work of Wilhelm His Sr., Santiago Ramón y Cajal and many others since the 19th century. They laid the foundation to identify the circuitry of the cerebellum, already revealing its stereotypic three-layered cortex and discerning several of its neuronal components. Their work was fundamental in the acceptance of the neuron doctrine, which acknowledges the key role of individual neurons in forming the basic units of the nervous system. Increasing evidence shows that the cerebellum performs a variety of homeostatic and higher order neuronal functions beyond the mere control of motor behaviour. Over the last three decades, many studies have revealed the molecular machinery that regulates distinct aspects of cerebellar development, from the establishment of a cerebellar anlage in the posterior brain to the identification of cerebellar neuron diversity at the single cell level. In this review, we focus on summarizing our current knowledge on early cerebellar development with a particular emphasis on the molecular determinants that secure neuron specification and contribute to the diversity of cerebellar neurons.

The revolutionary developmental biology of Wilhelm His, Sr.

ABSTRACTSwiss‐born embryologist Wilhelm His, Sr. (1831–1904) was the first scientist to study embryos using paraffin histology, serial sectioning and three‐dimensional modelling. With these techniques, His made many important discoveries in vertebrate embryology and developmental neurobiology, earning him two Nobel Prize nominations. He also developed several theories of mechanical and evolutionary developmental biology. His argued that adult form is determined by the differential growth of developmental primordia. Furthermore, he suggested that changes in the growth parameters of those primordia are responsible for generating new phenotypes during evolution. His developed these theories in his book ‘Our Bodily Form’ (Unsere Körperform). Here, we review His's work with special emphasis on its potential importance to the disciplines of evolutionary developmental biology (evo‐devo) and mechanobiology.

Wilhelm His Sr. and the development of paraffin embedding.

Paraffin histology is one of the most important and commonly-used laboratory techniques in diagnostic histopathology. The discovery of paraffin embedding is often attributed to the pathologist Edwin Klebs. Klebs was following the lead of Stricker, who embedded embryos in a mixture of hot stearin and white beeswax. We show that Klebs experimented with paraffin wax for embedding tumour tissue. But he quickly rejected it as unsuitable because paraffin wax did not infiltrate the tissue. One of Klebs’ correspondents, embryologist Wilhelm His, Sr., learned of Klebs’ experiments and decided to try paraffin embedding. His dehydrated chicken embryos in alcohol, cleared them in lavender oil, and dripped hot paraffin wax onto them. This process allowed His to cut good sections. Here, we have replicated His’s paraffin embedding protocol in order to determine whether His had indeed made the landmark discovery of infiltration embedding with paraffin wax. We followed the protocol that he gives in his 1868 monograph on the early development of the chicken. The protocol described by His failed, in our hands, to yield sections of the quality that he illustrates in his monograph. Typically, the tissue disintegrated when sectioned due to poor infiltration of the wax. Usable sections could only be obtained if His’s protocol was modified by melting the embedded embryos in fresh paraffin wax. One explanation for our findings is that we failed to faithfully replicate His’s protocol. Another is that his protocol was incomplete. We suggest that His is likely to have discovered and perfected infiltration embedding with paraffin wax but did not publish a complete protocol.Supplementary InformationThe online version of this article (10.1007/s00292-021-00947-4) contains supplementary material, which is available to authorized users.

Wilhelm His, Sr., and the development of paraffin embedding. German version

Die paraffinbasierte histologische Untersuchung ist eines der wichtigsten angewendeten Laborverfahren in der diagnostischen Histopathologie. Die Entwicklung der Paraffineinbettung wird oft dem Pathologen Edwin Klebs zugeschrieben. Klebs orientierte sich an den Arbeiten von Stricker, der Embryonen in eine Mischung aus heißem Tristearin und weißem Bienenwachs einbettete, und experimentierte mit Paraffin, um Tumorgewebe einzubetten. Er verwarf den Ansatz aber rasch, da Paraffin das Gewebe nicht infiltrierte. Klebs stand im Briefwechsel mit dem Embryologen Wilhelm His Senior, der von dessen Experimenten erfuhr und beschloss, sich an der Paraffineinbettung zu versuchen. His entwässerte Hühnerembryonen in Alkohol, klärte sie mit Lavendelöl und träufelte heißes Paraffin darüber. Dieses Verfahren ermöglichte ihm die Anfertigung guter Schnitte. In der vorliegenden Arbeit haben wir His’ Protokoll der Paraffineinbettung nachvollzogen, um zu ermitteln, ob His tatsächlich die Infiltrationseinbettung mit Paraffin gelungen ist. Wir befolgten das Protokoll aus seiner 1868 erschienenen Monografie. Anhand der Anweisungen von His gelang es uns nicht, Schnitte mit der von ihm illustrierten Qualität herzustellen. In der Regel zerfiel das Gewebe beim Schneiden wegen schlechter Wachsinfiltration. Brauchbare Schnitte wurden nur bei Abwandlung von His’ Protokoll durch das Wiedereinschmelzen der eingebetteten Embryos in frischem Paraffin erreicht. Möglicherweise ist es uns nicht gelungen ist, das Protokoll von His detailgetreu zu replizieren, oder das Protokoll war unvollständig. Nach unserer Einschätzung hat His wahrscheinlich die Infiltrationseinbettung mit Paraffin erfunden und perfektioniert, aber kein vollständiges Protokoll veröffentlicht.Zusatzmaterial onlineZusätzliche Informationen „Das histologische Verfahren von His“ Originalfassung aus [15] sind in der Online-Version dieses Artikels (10.1007/s00292-021-00943-8) enthalten.

Chapter 2 - History of hypothalamic research: “The spring of primitive existence”

The central brain region of interest for neuroendocrinology is the hypothalamus, a name coined by Wilhelm His in 1893. Neuroendocrinology is the discipline that studies hormone production by neurons, the sensitivity of neurons for hormones, as well as the dynamic, bidirectional interactions between neurons and endocrine glands. These interactions do not only occur through hormones, but are also partly accomplished by the autonomic nervous system that is regulated by the hypothalamus and that innervates the endocrine glands. A special characteristic of the hypothalamus is that it contains neuroendocrine neurons projecting either to the neurohypophysis or to the portal vessels of the anterior lobe of the pituitary in the median eminence, where they release their neuropeptides or other neuroactive compounds into the bloodstream, which subsequently act as neurohormones. In the 1970s it was found that vasopressin and oxytocin not only are released as hormones in the circulation but that their neurons project to other neurons within and outside the hypothalamus and function as neurotransmitters or neuromodulators that regulate central functions, including the autonomic innervation of all our body organs. Recently magnocellular oxytocin neurons were shown to send not only an axon to the neurohypophysis, but also axon collaterals of the same neuroendocrine neuron to a multitude of brain areas. In this way, the hypothalamus acts as a central integrator for endocrine, autonomic, and higher brain functions. The history of neuroendocrinology is described in this chapter from the descriptions in De humani corporis fabrica by Vesalius (1537) to the present, with a timeline of the scientists and their findings.

News

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The role of teratogens in neural crest development.

The neural crest (NC), discovered by Wilhelm His 150 years ago, gives rise to a multipotent migratory embryonic cell population that generates a remarkably diverse and important array of cell types during the development of the vertebrate embryo. These cells originate in the neural plate border (NPB), which is the ectoderm between the neural plate and the epidermis. They give rise to the neurons and glia of the peripheral nervous system, melanocytes, chondrocytes, smooth muscle cells, odontoblasts and neuroendocrine cells, among others. Neurocristopathies are a class of congenital diseases resulting from the abnormal induction, specification, migration, differentiation or death of NC cells (NCCs) during embryonic development and have an important medical and societal impact. In general, congenital defects affect an appreciable percentage of newborns worldwide. Some of these defects are caused by teratogens, which are agents that negatively impact the formation of tissues and organs during development. In this review, we will discuss the teratogens linked to the development of many birth defects, with a strong focus on those that specifically affect the development of the NC, thereby producing neurocristopathies. Although increasing attention is being paid to the effect of teratogens on embryonic development in general, there is a strong need to critically evaluate the specific role of these agents in NC development. Therefore, increased understanding of the role of these factors in NC development will contribute to the planning of strategies aimed at the prevention and treatment of human neurocristopathies, whose etiology was previously not considered.

Filling in the phylogenetic gaps: Induction, migration, and differentiation of neural crest cells in a squamate reptile, the veiled chameleon (Chamaeleo calyptratus).

Neural crest cells comprise a migratory progenitor cell population that differentiate into cell types such as neurons and glia of the peripheral nervous system, pigment cells, hormone secreting cells in glands, and skeletal and connective tissue in the head, thus making important contributions to most tissues and organs throughout the vertebrate body. The evolutionary appearance of neural crest cells is considered synonymous with the origin of vertebrates and their subsequent diversification and radiation. While the comparative biology of neural crest cells has been studied for a century and a half beginning with their discovery by Wilhelm His in 1868, most of our understanding of their development and function has come from a small number of species. Thus, critical gaps exist in our understanding of how neural crest cells mediate evolution and development. This is particularly true with respect to squamate reptiles (lizards, snakes, amphisbaenians), which account for approximately one-third of all living tetrapods. Here, we present veiled chameleons (Chamaeleo calyptratus) as a model system for studying neural crest cell development in squamates. Chameleons exhibit various morphological specializations associated with an arboreal lifestyle that may have been facilitated through neural crest cells acting as a conduit for evolutionary change.

The Anatomy, Development, and Evolution of the Atrioventricular Conduction Axis.

It is now well over 100 years since Sunao Tawara clarified the location of the axis of the specialised myocardium responsible for producing coordinated ventricular activation. Prior to that stellar publication, controversies had raged as to how many bundles crossed the place of the atrioventricular insulation as found in mammalian hearts, as well as the very existence of the bundle initially described by Wilhelm His Junior. It is, perhaps surprising that controversies continue, despite the multiple investigations that have taken place since the publication of Tawara’s monograph. For example, we are still unsure as to the precise substrates for the so-called slow and fast pathways into the atrioventricular node. Much has been done, nonetheless, to characterise the molecular make-up of the specialised pathways, and to clarify their mechanisms of development. Of this work itself, a significant part has emanated from the laboratory coordinated for a quarter of a century by Antoon FM Moorman. In this review, which joins the others in recognising the value of his contributions and collaborations, we review our current understanding of the anatomy, development, and evolution of the atrioventricular conduction axis.

A chemotactic model of trunk neural crest cell migration.

Trunk neural crest cells follow a common ventral migratory pathway but are distributed into two distinct locations to form discrete sympathetic and dorsal root ganglia along the vertebrate axis. Although fluorescent cell labeling and time-lapse studies have recorded complex trunk neural crest cell migratory behaviors, the signals that underlie this dynamic patterning remain unclear. The absence of molecular information has led to a number of mechanistic hypotheses for trunk neural crest cell migration. Here, we review recent data in support of three distinct mechanisms of trunk neural crest cell migration and develop and simulate a computational model based on chemotactic signaling. We show that by integrating the timing and spatial location of multiple chemotactic signals, trunk neural crest cells may be accurately positioned into two distinct targets that correspond to the sympathetic and dorsal root ganglia. In doing so, we honor the contributions of Wilhelm His to his identification of the neural crest and extend the observations of His and others to better understand a complex question in neural crest cell biology.

Historical perspective on neuroembryology: Wilhelm His and his contemporaries.

This year marks the 150th anniversary of the discovery of the neural crest by Wilhelm His (1831-1904). Beyond this discovery, His made possible the program of comparative anatomy at the cellular level thanks to the introduction in 1866 of the first microtome to have micrometer advance. His studies of the origin, migration, and fate of neural crest cells were foundational in the field of neuroembryology and contributed to the establishment of the neuron doctrine. The article places His' work in the scientific context of 19th century embryology, concerned with reconciling the embryonic layers theory, the cell theory and the evolution theory. From a methodological point of view, the article shows that His appears in this context at the junction of two embryological traditions, the descriptive morphological approach and the new experimental approach. The anatomical and physiological exploration of the neural crest and the controversies that followed highlight the transition between these two traditions that His enabled and of which he was one of the initiators.

Neural crest delamination and migration: Looking forward to the next 150 years

Neural crest (NC) cells were described for the first time in 1868 by Wilhelm His. Since then, this amazing population of migratory stem cells has been intensively studied. It took a century to fully unravel their incredible abilities to contribute to nearly every organ of the body. Yet, our understanding of the cell and molecular mechanisms controlling their migration is far from complete. In this review, we summarize the current knowledge on epithelial-mesenchymal transition and collective behavior of NC cells and propose further stops at which the NC train might be calling in the near future.

Germ layers, the neural crest and emergent organization in development and evolution.

Discovered in chick embryos by Wilhelm His in 1868 and named the neural crest by Arthur Milnes Marshall in 1879, the neural crest cells that arise from the neural folds have since been shown to differentiate into almost two dozen vertebrate cell types and to have played major roles in the evolution of such vertebrate features as bone, jaws, teeth, visceral (pharyngeal) arches, and sense organs. I discuss the discovery that ectodermal neural crest gave rise to mesenchyme and the controversy generated by that finding; the germ layer theory maintained that only mesoderm could give rise to mesenchyme. A second topic of discussion is germ layers (including the neural crest) as emergent levels of organization in animal development and evolution that facilitated major developmental and evolutionary change. The third topic is gene networks, gene co-option, and the evolution of gene-signaling pathways as key to developmental and evolutionary transitions associated with the origin and evolution of the neural crest and neural crest cells.

The 125th anniversary of the His bundle discovery.

In 1893, Wilhelm His Jr. was the first to describe the AV (atrioventricular) bundle of the vertebrate heart, which now bears his name. Moreover, prior to the turn of the century, W.His Jr. had proved the function of the AV bundle by transection experiments in animals, and had interpreted Adams Stokes disease as heart block due to pathological changes within the bundle. In this way, he was ahead of his time. While clinical interest was limited to the bundle as the location of an AV block in the first half of the 125years, it has gained attractiveness since then as atarget of diagnostic and therapeutic procedures. The introduction of His bundle electrography relaunched the interest in cardiac arrhythmias. Once the AV bundle could be localized clinically, its ablation, and in recent times its permanent stimulation, became options in the therapy of well-defined arrhythmia and conduction problems.

Wilhelm His and mechanistic approaches to development at the time of Entwicklungsmechanik.

At the end of the nineteenth century, approaches from experimental physiology made inroads into embryological research. A new generation of embryologists felt urged to study the mechanisms of organ formation. This new program, most prominently defended by Wilhelm Roux (1850-1924), was called Entwicklungsmechanik. Named variously as "causal embryology", "physiological embryology" or "developmental mechanics", it catalyzed the movement of embryology from a descriptive science to one exploring causal mechanisms. This article examines the specific scientific and epistemological meaning of the mechanistic approaches of embryological development by focusing on Wilhelm His' (1831-1904) histogenetic work. Roux was neither the first, nor the only one to argue for an experimental exploration of causes in embryology. At the time of Roux, physiological explanations of the genesis of the anatomical forms were developing in parallel, not only in German-speaking countries, but in France, Switzerland and English-speaking countries as well. The experimental approach and the cellular descriptions of embryogenesis were already omni-present when Roux proposed his Entwicklungsmechanik. However, these approaches remained disjointed. It appears that it was Wilhelm His who first succeeded in combining the question of the causal factors determining epigenesis, which was closely connected with experimentation on, and cellular descriptions of, development, in a coherent and concrete synthesis, making him one of the true initiators of the developmental mechanics.

Annals of morphology fields and prepatterns. Editorial Festschrift for John C. Carey, MD, MPH.

The investigation of mammalian malformations began to approach human needs in the 19th century with, for example, Meckel's dissection of sibs with the "Meckel" syndrome, his intimation of Heredität as cause of the condition, his conclusion as to the common causal origin of this specific combination of congenital anomalies, the clear enunciation of the concept of primary malformations, the recognition that many human malformations are normal developmental states in other animals, and that some were normal anatomical states in remote ancestors and now still normal in collateral descendants (atavisms, Darwin's "reversions"; for example, four wings in dipterans, normal in dragonflies and their common ancestor). Later in the century, Wilhelm His Sr. had proposed a schematic map of "organ-forming districts" for prospective chick development, a concept that did not sit well with early workers in developmental biology (e.g., Boveri) until methods became available for a direct experimental "attack" on the embryo. This approach was pioneered by Spemann and Mangold through interspecies transplantation of embryonic rudiments with the spectacular result that set the research stage in developmental biology for the next many years. But it was not until mid-century that the late, great geneticist, Curt Stern, made the His model of chick development more intellectually and experimentally approachable with his meticulous analysis of cuticular appendages of Drosophila, one bristle and one bristle group (field) at a time, in mosaics or gynandromorphs, leading to the ingenious concept of prepatterns. As a basic scientist, Stern did not broaden prepatterns into medicine or to human malformations where it has now found a most gratifying application. This contribution to the Carey Festschrift is to summarize, briefly, field and prepattern theory. © 2016 Wiley Periodicals, Inc.