Spatial mechanisms of gene regulation in metazoan embryos

The basic characteristics of embryonic process throughout Metazoa are considered with focus on those aspects that provide insight into how cell specification occurs in the initial stages of development. There appear to be three major types of embryogenesis: Type 1, a general form characteristic of most invertebrate taxa of today, in which lineage plays an important role in the spatial organization of the early embryo, and cell specification occurs in situ, by both autonomous and conditional mechanisms; Type 2, the vertebrate form of embryogenesis, which proceeds by mechanisms that are essentially independent of cell lineage, in which diffusible morphogens and extensive early cell migration are particularly important; Type 3, the form exemplified by long germ band insects in which several different regulatory mechanisms are used to generate precise patterns of nuclear gene expression prior to cellularization. Evolutionary implications of the phylogenetic distribution of these types of embryogenesis are considered. Regionally expressed homeodomain regulators are utilized in all three types of embryo, in similar ways in later and postembryonic development, but in different ways in early embryonic development. A specific downstream molecular function for this class of regulator is proposed, based on evidence obtained in vertebrate systems. This provides a route by which to approach the comparative regulatory strategies underlying the three major types of embryogenesis

The last common bilaterian ancestor

Many regulatory genes appear to be utilized in at least superficially similar ways in the development of particular body parts in Drosophila and in chordates. These similarities have been widely interpreted as functional homologies, producing the conventional view of the last common protostome-deuterostome ancestor (PDA) as a complex organism that possessed some of the same body parts as modern bilaterians. Here we discuss an alternative view, in which the last common PDA had a less complex body plan than is frequently conceived. This reconstruction alters expectations for Neoproterozoic fossil remains that could illustrate the pathways of bilaterian evolution

Fin development in a cartilaginous fish and the origin of vertebrate limbs

Recent fossil finds and experimental analysis of chick and mouse embryos highlighted the lateral fin fold theory, which suggests that two pairs of limbs in tetrapods evolved by subdivision of an elongated single fin1. Here we examine fin development in embryos of the primitive cartilaginous fish, Scyliorhinus canicula (dogfish) using scanning electron microscopy and investigate expression of genes known to be involved in limb positioning, identity and patterning in higher vertebrates. Although we did not detect lateral fin folds in dogfish embryos, Engrailed-1 expression suggests that the body is compartmentalized dorso-ventrally. Furthermore, specification of limb identity occurs through the Tbx4 and Tbx5 genes, as in higher vertebrates. In contrast, unlike higher vertebrates, we did not detect Shh transcripts in dogfish fin-buds, although dHand (a gene involved in establishing Shh) is expressed. In S. canicula, the main fin axis seems to lie parallel to the body axis. 'Freeing' fins from the body axis and establishing a separate 'limb' axis has been proposed to be a crucial step in evolution of tetrapod limbs2, 3. We suggest that Shh plays a critical role in this process

Molecular and cellular mechanisms underlying the evolution of form and function in the amniote jaw.

The amniote jaw complex is a remarkable amalgamation of derivatives from distinct embryonic cell lineages. During development, the cells in these lineages experience concerted movements, migrations, and signaling interactions that take them from their initial origins to their final destinations and imbue their derivatives with aspects of form including their axial orientation, anatomical identity, size, and shape. Perturbations along the way can produce defects and disease, but also generate the variation necessary for jaw evolution and adaptation. We focus on molecular and cellular mechanisms that regulate form in the amniote jaw complex, and that enable structural and functional integration. Special emphasis is placed on the role of cranial neural crest mesenchyme (NCM) during the species-specific patterning of bone, cartilage, tendon, muscle, and other jaw tissues. We also address the effects of biomechanical forces during jaw development and discuss ways in which certain molecular and cellular responses add adaptive and evolutionary plasticity to jaw morphology. Overall, we highlight how variation in molecular and cellular programs can promote the phenomenal diversity and functional morphology achieved during amniote jaw evolution or lead to the range of jaw defects and disease that affect the human condition

NASA Developmental Biology Workshop: A summary

The Life Sciences Division of the National Aeronautics and Space Administration (NASA) as part of its continuing assessment of its research program, convened a workshop on Developmental Biology to determine whether there are important scientific studies in this area which warrant continued or expanded NASA support. The workshop consisted of six panels, each of which focused on a single major phylogenetic group. The objectives of each panel were to determine whether gravity plays a role in the ontogeny of their subject group, to determine whether the microgravity of spaceflight can be used to help understand fundamental problems in developmental biology, to develop the rationale and hypotheses for conducting NASA-relevant research in development biology both on the ground and in space, and to identify any unique equipment and facilities that would be required to support both ground-based and spaceflight experiments

Analysis of craniofacial defects in Six1/Eya1-associated Branchio-Oto-Renal Syndrome

Poster Session I - Morphogenesis: 205/B10117th ISDB 2013 cum 72nd Annual Meeting of the Society for Developmental Biology, 7th Latin American Society of Developmental Biology Meeting and 11th Congreso de la Sociedad Mexicana de Biologia del Desarrollo.Branchio-Oto-Renal (BOR) syndrome patients exhibit craniofacial and renal anomalies as well as deafness. BOR syndrome is caused by mutations in Six1 or Eya1, both of which regulate cell proliferation and differentiation. The molecular mechanism underlying the craniofacial and branchial arch (BA) defects in BOR syndrome is unclear. We have found that Hoxb3 is up-regulated in the second branchial arch (BA2) of Six1-/- mutants. Moreover, Hoxb3 over-expression in transgenic mice leads to BA abnormalities which are similar to the BA defects in Six1-/- or Eya1-/- mutants, suggesting a regulatory relationship among Six1, Eya1 and Hoxb3 genes. The aim of this study is to investigate the molecular mechanism underlying abnormal BA development in BOR syndrome using Six1 and Eya1 mutant mice. Two potential Six1 binding sites were identified on the Hoxb3 gene. In vitro and in vivo Chromatin IP assays showed that Six1 could directly bind to one of the sites specifically. Furthermore, using a chick in ovo luciferase assay we showed that Six1 could suppress gene expression through one of the specific binding sites. On the other hand, in Six1-/- mutants, we found that the Notch ligand Jag1 was up-regulated in BA2. Similarly, in Hoxb3 transgenic mice, ectopic expression of Jag1 could be also detected in BA2. To investigate the activation of Notch signaling pathway, we found that Notch intracellular domain (NICD), a direct indicator of Notch pathway activation, was up-regulated in BAs of Six1-/-; Eya1-/- double mutants. Our results indicate that Hoxb3 and Notch signaling pathway are involved in mediating the craniofacial defects of Six1/Eya1-associated Branchio-Oto-Renal Syndrome.postprin

Sox10 regulates enteric neural crest cell migration in the developing gut

Concurrent Sessions 1: 1.3 - Organs to organisms: Models of Human Diseases: abstract no. 1417th ISDB 2013 cum 72nd Annual Meeting of the Society for Developmental Biology, VII Latin American Society of Developmental Biology Meeting and XI Congreso de la Sociedad Mexicana de Biologia del Desarrollo. The Conference's web site is located at http://www.inb.unam.mx/isdb/Sox10 is a HMG-domain containing transcription factor which plays important roles in neural crest cell survival and differentiation. Mutations of Sox10 have been identified in patients with Waardenburg-Hirschsprung syndrome, who suffer from deafness, pigmentation defects and intestinal aganglionosis. Enteric neural crest cells (ENCCs) with Sox10 mutation undergo premature differentiation and fail to colonize the distal hindgut. It is unclear, however, whether Sox10 plays a role in the migration of ENCCs. To visualize the migration behaviour of mutant ENCCs, we generated a Sox10NGFP mouse model where EGFP is fused to the N-terminal domain of Sox10. Using time-lapse imaging, we found that ENCCs in Sox10NGFP/+ mutants displays lower migration speed and altered trajectories compared to normal controls. This behaviour was cell-autonomous, as shown by organotypic grafting of Sox10NGFP/+ gut segments onto control guts and vice versa. ENCCs encounter different extracellular matrix (ECM) molecules along the developing gut. We performed gut explant culture on various ECM and found that Sox10NGFP/+ ENCCs tend to form aggregates, particularly on fibronectin. Time-lapse imaging of single cells in gut explant culture indicated that the tightly-packed Sox10 mutant cells failed to exhibit contact inhibition of locomotion. We determined the expression of adhesion molecule families by qPCR analysis, and found integrin expression unaffected while L1-cam and selected cadherins were altered, suggesting that Sox10 mutation affects cell adhesion properties of ENCCs. Our findings identify a de novo role of Sox10 in regulating the migration behaviour of ENCCs, which has important implications for the treatment of Hirschsprung disease.postprin