Limb Development

Mathematical Modelling has a long history in developmental biology. Advances in experimental techniques and computational algorithms now permit the development of increasingly more realistic models of organogenesis. In particular, 3D geometries of developing organs have recently become available. In this paper, we show how to use image-based data for simulations of organogenesis in COMSOL Multiphysics. As an example, we use limb bud development, a classical model system in mouse developmental biology. We discuss how embryonic geometries with several subdomains can be read into COMSOL using the Matlab LiveLink, and how these can be used to simulate models on growing embryonic domains. The ALE method is used to solve signaling models even on strongly deforming domains.

Introduction Chronic inflammatory demyelinating polyradiculoneu-ropathy (CIDP) is an uncommon progressive or relapsing paralyzing disease caused by inflammation of the periph-eral nerves, and is a potentially treatable disease with an estimated prevalence of about 0.5 ...

The California Tree Failure Report Program database was established in 1987 to collect data on tree branch, trunk, and root breakage or uprooting. The database for the CTFRP is compiled from failure evaluation reports filled out by statewide cooperating arborists, tree assessors, and other horticultural professionals. Compilation of 186 reports for Monterey pine (Pinus radiata) has permitted development of a

The morphological diversity of the vertebrate limb is the result of finely tuned responses to signals that emanate from organizer centers controlling the three embryonic axes that shape the limb throughout processes such as apoptosis, differential growth and cell differentiated group of cells subjacent to the Apical Ectodermal Ridge (AER) respond to chondrogenic or proapoptotic signals...

The engrailed gene is a transcription factor required in numerous species for major developmental steps (neurogenesis, limb development, boundary establishment), and its evolution is known to be closely related to the evolution of the metazoan body plan. Cephalopods exhibit numerous morphological peculiarities among molluscs, such as a direct development, a complex sensory and nervous system (eyes, brain, giant axons), a reduced shell, a funnel, and a brachial crown. We assessed a potential recruitment of engrailed in the development of these derived traits and examined the expression pattern of engrailed during the organogenesis of the cuttlefish Sepia officinalis, by immunostaining. Engrailed was detected at the margin of the prospective internal shell, which is consistent with studies on molluscs having an external shell and confirms a conserved role of engrailed in delimitating the molluscan shell compartment. Interestingly, unexpected patterns were early detected in the emerging arms, funnel and optic vesicles and latter in tentacles and eye lids. We also identified an engrailed cognate in the squid Loligo, which provides new evidence that engrailed in molluscs is not restricted to a ‘shell function’ and has been recruited in the mollusc lineage for the emergence of morphological novelties in cephalopods.

During the hand plate development, the processes of cell differentiation and control of cell death are relevant to ensure a correct shape of the limb. The progenitor cell pool that later will differentiate into cartilage to form the digits arises from undifferentiated into cartilage to form the digits arises from undifferentiated mesenchymal cells beneath the apical ectodermal ridge (AER). Once these cells abandon the area of influence of signals from AER and ectoderm, some cells are committed to chondrocyte lineage forming the digital rays. However, if the cells are not committed to chondrocyte lineage, they will form the prospective interdigits that in species with free digits will subsequently die...

Modern crocodilians and birds are the only living representatives of the Archosauria, a group that also includes non-avian dinosaurs and pterosaurs. Modern crocodilians originated during the early Cretaceous period and dispersed globally. Examples of physiological similarities between living crocodilians and birds include similar amino acids in β-keratins among crocodiles, turtles and birds; oviduct homologies between crocodilians and birds; similar forelimb structures in crocodiles and other archosaurs and similarities in gene expression in limb development in alligators and chickens. While individual crocodilian species have adapted their behaviours to meet specific strategies for survival in specific habitats, core reproductive behaviours are universal among modern crocodilians and transcend speciation, morphology and geographic distribution. Hard-wired core behaviours include social signals that incorporate chemosensory, auditory and mechanoreception modalities; construction of a temperature-stabilising nest chamber to incubate eggs; and parental care of their young. Parental care may reflect a primitive character for archosaurs, including dinosaurs. Crocodilians use integumentary sense organs (ISOs) during courtship and in parental care, and similar structures may have had similar functions in dinosaurs. The presence of numerous foramina (possible ISOs) in the skulls of saurischians, along with the findings of fossilised nests with adults, may indicate similar complex behaviours, including parental care, in dinosaurs.

The balancer is a larval appendage whose taxonomic distribution is limited to approximately half of the species found in three of the ten families of salamanders. These organs are small projections from the region of the jaw joint that are present before limbs develop; they apparently function in mechanical support and chemical adhesion. Balancers are typically associated with species that are pond breeding, as opposed to stream breeding, and are therefore assumed to be adaptive in still water and non-functional in flowing water. However, many exceptions to this generalization exist. We explain this unusual distribution by combining morphological and natural history data with a phylogenetic analysis. Because the balancer has been little studied, we summarize the literature on morphology, development, variation, function, ontogenetic fate, ecological distribution, and homology. Using immunohistcxhemical methods we find that the balancer is a complex organ. The balancer contains a lay...

Control of dorsoventral patterns in the chick at the prelimb stages resides in the limb mesoderm. Recombination experiments at stage 14, with dorsoventrally reversed ectoderm, result in wings with mesodermal dorsoventral polarity. Similar recombinations at stage 16 show that the ectoderm has acquired dorsoventral information and can impose this polarity on the patterns of mesodermal differentiation in the distal regions of the wing. The dorsoventral information in the ectoderm comes from the mesoderm, which transfers this information to the overlying ectoderm between stages 14 and 16. The initial dorsoventral information in the ectoderm is not stable and can be reprogrammed by stage 14 mesoderm. Subsequently, there is a gradual stabilization of the ectodermal information. At the same time the mesoderm loses its capacity to reprogram dorsoventral information in the ectoderm.

The external morphology of limb development in Orchestia cavimana is examined by scanning electron microscopy and fluorescence staining from the appearance of the first limb buds until hatching. As other amphipods, O. cavimana undergoes direct development and the degree of segmental differentiation shows a more or less continual decrease in anteroposterior direction. Limbs form ventrally as small buds, which elongate and divide into podomeres early in development. This early subdivision largely corresponds with the limb segmentation of the hatchling. When the post-naupliar limbs start to develop, the germ band begins to split into two halves along the midline, so that the trunk limbs transiently occupy a very dorsolateral position. After the germ band has closed again, the differentiation into the characteristic amphipodan tagmata (cephalothorax, pereon, pleon) takes place and the limb podomeres lose their round-shape. The late embryo is covered by a so-called intermediate cuticle, which is formed after an embryonic moult and shed after hatching. The early development of O. cavimana reveals the Anlage of a vestigial seventh pleonic segment that is assumed to belong to the ground pattern of malacostracans, but is retained as a free, limbless segment only in adult Leptostraca. A transient subdivision of the proximal segment of the pleopods suggests the occurrence of a coxa and a basis in these limbs. The mandible attains its upright, adult position via a characteristic bending process that is strikingly similar to that in Archaeognatha (Insecta).

The balancer is a larval appendage whose taxonomic distribution is limited to approximately half of the species found in three of the ten families of salamanders. These organs are small projections from the region of the jaw joint that are present before limbs develop; they apparently function in mechanical support and chemical adhesion. Balancers are typically associated with species that are pond breeding, as opposed to stream breeding, and are therefore assumed to be adaptive in still water and non-functional in flowing water. However, many exceptions to this generalization exist. We explain this unusual distribution by combining morphological and natural history data with a phylogenetic analysis. Because the balancer has been little studied, we summarize the literature on morphology, development, variation, function, ontogenetic fate, ecological distribution, and homology. Using immunohistcxhemical methods we find that the balancer is a complex organ. The balancer contains a lay...

Bats are the only mammals capable of powered flight, but little is known about the genetic determinants that shape their wings. Here, we generated a genome for Miniopterus natalensis and performed RNA-seq and ChIP-seq (H3K27ac, H3K27me3) on its developing forelimb and hindlimb autopods at sequential embryonic stages to decipher the molecular events that underlie bat wing development. Over 7,000 genes and several lncRNAs, including Tbx5-as1 and Hottip, were differentially expressed between forelimb, hindlimb and different stages. ChIP-seq identified thousands of regions that are differentially modified in forelimb versus hindlimb. Comparative genomics found 2,796 bat-accelerated regions within H3K27ac peaks, several of which cluster near limb-associated genes. Pathway analyses revealed multiple ribosomal proteins and known limb patterning signaling pathways as differentially regulated, and implicated increased forelimb mesenchymal condensations with differential growth. Combined, our work outlines multiple genetic components that contribute to bat wing formation, providing a genomic blueprint for this morphological innovation.

The mechanism that controls digit formation has long intrigued developmental and theoretical biologists, and many different models and mechanisms have been proposed. Here we review models of limb development with a specific focus on digit and long bone formation. Decades of experiments have revealed the basic signalling circuits that control limb development, and recent advances in imaging and molecular technologies provide us with unprecedented spatial detail and a broader view on the regulatory networks. Computational approaches are important to integrate the available information into a consistent framework that will allow us to achieve a deeper level of understanding and that will help with the future planning and interpretation of complex experiments, paving the way to in silico genetics. Previous models of development had to be focused on very few, simple regulatory interactions. Algorithmic developments and increasing computing power now enable the generation and validation o...