Brian K. Hall

All for one and one for all: condensations and the initiation of skeletal development.

Condensation is the pivotal stage in the development of skeletal and other mesenchymal tissues. It occurs when a previously dispersed population of cells gathers together to differentiate into a single cell/tissue type such as cartilage, bone, muscle, tendon, kidney, and lung and is the earliest stage during organ formation when tissue-specific genes are upregulated. We present a synopsis of our current understanding of how condensations are initiated and grown, how their boundaries and sizes are set, how condensation ceases, and how overt differentiation begins. Extracellular matrix molecules, cell surface receptors and cell adhesion molecules, such as fibronectin, tenascin, syndecan, and N-CAM, initiate condensation formation and set condensation boundaries. Hox genes (Hoxd-11-13) and other transcription factors (CFKH-1, MFH-1, osf-2), modulate the proliferation of cells within condensations. Cell adhesion is ensured indirectly through Hox genes (Hoxa-2, Hoxd-13), and directly via cell adhesion molecules (N-CAM and N-cadherin). Subsequent growth of condensations is regulated by BMPs, which activate Pax-2, Hoxa-2 and Hoxd-11 among other genes. Growth of a condensation ceases when Noggin inhibits BMP signalling, setting the stage for transition to the next stage of skeletal development, namely overt cell differentiation. BioEssays 22:138-147, 2000.

Buried alive : How osteoblasts become osteocytes

During osteogenesis, osteoblasts lay down osteoid and transform into osteocytes embedded in mineralized bone matrix. Despite the fact that osteocytes are the most abundant cellular component of bone, little is known about the process of osteoblast‐to‐osteocyte transformation. What is known is that osteoblasts undergo a number of changes during this transformation, yet retain their connections to preosteoblasts and osteocytes. This review explores the osteoblast‐to‐osteocyte transformation during intramembranous ossification from both morphological and molecular perspectives. We investigate how these data support five schemes that describe how an osteoblast could become entrapped in the bone matrix (in mammals) and suggest one of the five scenarios that best fits as a model. Those osteoblasts on the bone surface that are destined for burial and destined to become osteocytes slow down matrix production compared to neighbouring osteoblasts, which continue to produce bone matrix. That is, cells that continue to produce matrix actively bury cells producing less or no new bone matrix (passive burial). We summarize which morphological and molecular changes could be used as characters (or markers) to follow the transformation process. Developmental Dynamics 235:176–190, 2006.

The neural crest in development and evolution

Preface.- Discovery and Origins: Discovery Embryological Origins Evolutionary Origins Agnathans.- Derivatives and Diversity: Amphibians Bony and Cartilaginous Fishes Reptiles and Birds Mammals.- Mechanisms and Malformations: Mechanisms of Migration Mechanisms of Differentiation Neurocristopathies Birth Defects.- References.- Index.

Development and evolutionary origins of vertebrate skeletogenic and odontogenic tissues.

This review deals with the following seven aspects of vertebrate skeletogenic and odontogenic tissues.

The membranous skeleton: the role of cell condensations in vertebrate skeletogenesis

SummaryElements of the vertebrate skeleton are initiated as cell condensations, collectively termed the ‘membranous skeleton’ whether cartilages or bones by Grüneberg (1963). Condensations, which were identified as the basic cellular units in a recent model of morphological change in development and evolution (Atchley and Hall 1991) are reviewed in this paper. Condensations are initiated either by increased mitotic activity or by aggregation of cells towards a centre. Prechondrogenic (limb bud) and preosteogenic (scierai ossicle) condensations are discussed and contrasted. Both types of skeletogenic condensations arise following epithelial-mesenchymal interactions; condensations are identified as the first cellular product of such tissue interactions. Molecular characteristics of condensations are discussed, including peanut agglutinin lectin, which is used to visualize prechondrogenic condensations, and hyaluronan, hyaladherins, heparan sulphate proteoglycan, chondroitin sulphate proteoglycan, versican, tenascin, syndecan, N-CAM, alkaline phosphatase, retinoic acid and homeobox-containing genes. The importance for the initiation of chondrogenesis or osteogenesis of upper and lower limits to condensation size and the numbers of cells in a condensation are discussed, as illustrated by in vitro studies and by mutant embryos, including Talpid3 in the chick and Brachypod, Congenital hydrocephalus and Phocomelia in the mouse. Evidence that genes specific to the skeletal type are selectively activated at condensation is discussed, as is a recent model involving TGF-β and fibronectin in condensation formation. Condensations emerge as a pivotal stage in initiation of the vertebrate skeleton in embryonic development and in the modification of skeletal morphology during evolution.

Descent with modification: the unity underlying homology and homoplasy as seen through an analysis of development and evolution

Homology is at the foundation of comparative studies in biology at all levels from genes to phenotypes. Homology similarity because of common descent and ancestry, homoplasy is similarity arrived at via independent evolution However, given that there is but one tree of life, all organisms, and therefore all features of organisms, share degree of relationship and similarity one to another. That sharing may be similarity or even identity of structure the sharing of a most recent common ancestor–as in the homology of the arms of humans and apes–or it reflect some (often small) degree of similarity, such as that between the wings of insects and the wings of groups whose shared ancestor lies deep within the evolutionary history of the Metazoa. It may reflect sharing entire developmental pathways, partial sharing, or divergent pathways. This review compares features classified homologous with the classes of features normally grouped as homoplastic, the latter being convergence, parallelism, reversals, rudiments, vestiges, and atavisms. On the one hand, developmental mechanisms may be conserved, when a complete structure does not form (rudiments, vestiges), or when a structure appears only in some individuals (atavisms). On the other hand, different developmental mechanisms can produce similar (homologous) features Joint examination of nearness of relationship and degree of shared development reveals a continuum within expanded category of homology, extending from homology → reversals → rudiments → vestiges → atavisms → parallelism, with convergence as the only class of homoplasy, an idea that turns out to be surprisingly old. realignment provides a glimmer of a way to bridge phylogenetic and developmental approaches to homology homoplasy, a bridge that should provide a key pillar for evolutionary developmental biology (evo‐devo). It will and in a practical sense cannot, alter how homoplastic features are identified in phylogenetic analyses. But rudiments, reversals, vestiges, atavisms and parallelism as closer to homology than to homoplasy should guide toward searching for the common elements underlying the formation of the phenotype (what some have called deep homology of genetic and/or cellular mechanisms), rather than discussing features in terms of shared independent evolution.

The neural crest as a fourth germ layer and vertebrates as quadroblastic not triploblastic.

Next to cells, germ layers—the fundamental embryonic celllayers from which tissues and organs form—are the mostlong-standing units of structural organization of the embryosof multicellular animals (metazoans). First identified inchicken embryos by Pander in 1817, the history of germ lay-ers through the nineteenth century was one of increasing ap-preciation of their generality and importance:• layers equivalent to those in the chick were found byRathke (1825) in a decapod crustacean;• von Baer (1828) discovered germ layers in the em-bryos of vertebrates other than the chicken;• Huxley (1849) showed that the outer and inner layersof vertebrate embryos, which George Allman in 1853named “ectoderm” and “endoderm,” were homolo-gous with the two germ layers seen in adult coelenter-ates.Thus, Huxley, who coined the term “mesoderm” for themiddle layer, extended the germ layer concept from embryosto adults and from embryology to evolution, although it tookHuxley some time to appreciate the significance of his dis-covery. For decades, germ layers were the backdrop againstwhich research programs were initiated and the context intowhich new findings were inserted; see Hall (1998a, 1998b)for overviews.E. R. Lankester gave germ layer theory an even more sub-stantial role when in 1877 he divided the animal kingdominto three grades:• the Homoblastica (protozoa) had a uniform single“layer”;• coelenterates with two germ layers (ecto- and endo-derm) comprised the Diploblastica;• all other animals possessed three germ layers (ecto-,endo-, and mesoderm) and comprised the Triploblas-tica. Lankester’s scheme remains to this day: metazoans are re-garded as either diploblastic or triploblastic. My aim is to dem-onstrate that the neural crest, a layer of cells associated withthe developing neural tube and discovered in chick embryos in1868 but present in all vertebrate embryos (Hall 1999), is afourth germ layer, and that vertebrates (or more strictly crani- ates (vertebrates 1 hagfishes) are not triploblastic but quadro-blastic. What is the basis for such an apparent radical changeto a scheme that has stood for almost 125 years? A germ layer is a fundamental embryonic layer from whichtissues and organs arise. Ectoderm and endoderm are primarygerm layers. They are present from the outset of development,having been specified maternally during development of theegg (Gilbert 1997; Hall 1998b). Mesoderm is a secondary germlayer arising after fertilization, often only after inductive inter-actions between future ectoderm and endoderm (Hall 1998a,1998b, 1999). The neural crest, which is the dorsalmost portionof the neural folds in all vertebrate embryos, also arises second-arily, following inductive interactions between two types of ec-toderm—neural and epidermal (Fig. 1). Both mesoderm andneural crest break up into populations of cells that migrate awayfrom the midline to form a diversity of cell types (Hall 1999).Mesoderm is recognized as a germ layer because of thetremendous diversity of cell and tissue types that originatefrom it; mesoderm breaks up into recognized populations ofcells (sclerotome, dermamyotome, lateral plate, somatic, andsplanchnic mesoderm) and forms the same tissues and struc-tures across the animal kingdom. Neural crest breaks up intopopulations of cells that are conserved in all vertebrates andform the same tissues and organs across the vertebrates (Hall1999). Indeed, neural crest produces an even greater array ofcells and tissues than does mesoderm, including neural, pig-ment, skeletal, connective tissue, cardiac, dental, and endo-crine cells. Mesoderm and neural crest both give rise to em-bryonic mesenchyme. On all points, if mesoderm qualifies asa secondary germ layer, so does neural crest (Hall 1998a).

CELLULAR DIFFERENTIATION IN SKELETAL TISSUES

CONTENTS

Human cell type diversity, evolution, development, and classification with special reference to cells derived from the neural crest

Metazoans are composed of a finite number of recognisable cell types. Similar to the relationship between species and ecosystems, knowledge of cell type diversity contributes to studies of complexity and evolution. However, as with other units of evolution, the cell type often resists definition. This review proposes guidelines for characterising cell types and discusses cell homology and the various developmental pathways by which cell types arise, including germ layers, blastemata (secondary development/neurulation), stem cells, and transdifferentiation. An updated list of cell types is presented for a familiar, albeit overlooked model taxon, adult Homo sapiens, with 411 cell types, including 145 types of neurons, recognised. Two methods for organising these cell types are explored. One is the artificial classification technique, clustering cells using commonly accepted criteria of similarity. The second approach, an empirical method modeled after cladistics, resolves the classification in terms of shared features rather than overall similarity. While the results of each scheme differ, both methods address important questions. The artificial classification provides compelling (and independent) support for the neural crest as the fourth germ layer, while the cladistic approach permits the evaluation of cell type evolution. Using the cladistic approach we observe a correlation between the developmental and evolutionary origin of a cell, suggesting that this method is useful for predicting which cell types share common (multipotential) progenitors. Whereas the current effort is restricted by the availability of phenotypic details for most cell types, the present study demonstrates that a comprehensive cladistic classification is practical, attainable, and warranted. The use of cell types and cell type comparative classification schemes has the potential to offer new and alternative models for therapeutic evaluation.

A developmental study of the levels of progesterone, corticosterone, cortisol, and cortisone circulating in plasma of chick embryos

Abstract Blood plasma collected from chick embryos (9–20 days of incubation) and from 2-day-old chicks was deproteinized, extracted, and the steroid hormones separated by column chromatography. Progesterone, corticosterone, cortisol, and cortisone were isolated and their concentrations (ng/ml) determined using the competitive protein-binding globulin method of Murphy (1967). The combined concentration of the four hormones was 21.7 ng/ml plasma at 9 days, increased continuously during the latter half of the incubation period, reached a peak (82.5 ng/ml) near hatching, and declined after hatching. No one hormone predominated throughout the whole of the embryonic period, each hormone accounting for approximately 25% of the total concentration over the period studied. The change in concentration of the hormones with increasing age of the embryo did not follow a common pattern. Corticosterone and cortisol showed a significantly increased rate of accumulation beginning at 15 days of incubation. This was presumed to reflect activation of the pituitary-adrenal axis. Previous studies when only one hormone was assayed or when one hormone was used as a standard for total hormone concentration may require reevaluation in the light of our data.