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Signals for death and survival: a two-step mechanism for cavitation in the vertebrate embryo.

Conversion of a solid primordium to a hollow tube of cells is a morphogenetic process used frequently during vertebrate embryogenesis. In the early mouse embryo, this process of cavitation transforms the solid embryonic ectoderm into a columnar epithelium surrounding a cavity. Using both established cell lines and normal embryos, we provide evidence that cavitation in the early mouse embryo is the result of the interplay of two signals, one from an outer layer of endoderm cells that acts over short distances to create a cavity by inducing apoptosis of the inner ectodermal cells, and the other a rescue signal mediated by contact with the basement membrane that is required for the survival of the columnar cells that line the cavity. This simple model provides a paradigm for investigating tube morphogenesis in diverse developmental settings.

Amnion↗

Interaction between the signaling molecules WNT7a and SHH during vertebrate limb development: dorsal signals regulate anteroposterior patterning.

Growth and patterning of the vertebrate limb are controlled by the ridge, posterior mesenchyme, and non-ridge ectoderm. Fibroblast growth factor 4 (FGF4) and Sonic hedgehog (SHH) can mediate signaling from the ridge and posterior mesenchyme, respectively. Here we show that dorsal ectoderm is required together with FGF4 to maintain Shh expression. Removal of dorsal ectoderm results in loss of posterior skeletal elements, which can be rescued by exogenous SHH. Wnt7a, which is expressed in dorsal ectoderm, provides the signal required for Shh expression and formation of posterior structures. These results provide evidence that all three axes (dorsoventral, proximodistal, and anteroposterior) are intimately linked by the respective signals WNT7a, FGF4, and SHH during limb out-growth and patterning.

Animals↗

The T genes in embryogenesis.

Since its identification in 1927, the mouse T (Brachyury) locus has been implicated in mesoderm formation and notochord differentiation. Recent work has demonstrated that this gene encodes a putative transcription factor expressed specifically in nascent mesoderm and in the differentiating notochord. Homologous genes have been cloned from the frog Xenopus laevis, the zebrafish Brachydanio rerio and the ascidian Halocynthia roretzi. The T gene is an important tool for elucidating mesoderman and embryonic pattern formation.

Animals↗

Growth factors as morphogens: do gradients and thresholds establish body plan?

Theories of morphogenesis have centred around gradients of morphogens interpreted by cells according to preset concentration thresholds. Growth factor proteins have been candidates for such morphogens, and experiments in the frog Xenopus, among other organisms, now show that embryonic cells are capable of interpreting growth factor concentrations according to the models. This opens up questions of whether such mechanisms are sufficient, and-if there are growth factor gradients-which factors are actually used and how.

Animals↗

Fibroblast growth factors in mammalian development.

Polypeptide growth factors are secreted signalling molecules that function as intercellular communicators. Detailed analyses of the expression and function of members of the fibroblast growth factor (FGF) family and their recepotors have demonstrated that the FGF signalling pathways play essential roles in regulating cellular proliferation, differentiation and tissue patterning during vertebrate embryogenesis. Recent studies on the molecular basis of human dysmorphic syndromes have revealed that aberrant FGF signalling during limb and skeletal development can lead to pathogenesis.

Achondroplasia↗

Signalling by hedgehog family proteins in Drosophila and vertebrate development.

Members of the hedgehog gene family encode a novel class of secreted proteins and are expressed in embryonic cells known to possess important signalling activities in organisms as diverse as flies and chickens. Proteins of the hedgehog family act in these different developmental contexts as both permissive and instructive signals. How this signalling activity is transduced is (as yet) poorly understood, but recent studies point to the involvement of protein kinase A in both Drosophila and vertebrates.

Animals↗

Context-dependent neuronal differentiation and germ layer induction of Smad4-/- and Cripto-/- embryonic stem cells.

Activation of transforming growth factor-beta (TGF-beta) receptors typically elicits mesodermal development, whereas inhibition of this pathway induces neural fates. In vitro differentiated mouse embryonic stem (ES) cells with deletion of the TGF-beta pathway-related factors Smad4 or Cripto exhibited increased numbers of neurons. Cripto-/- ES cells developed into neuroecto-/epidermal cell types, while Smad4-/- cells also displayed mesodermal differentiation. ES cell differentiation into catecholaminergic neurons showed that these ES cells retained their ability to develop into dopaminergic and serotonergic neurons with typical expression patterns of midbrain and hindbrain genes. In vivo, transplanted ES cells to the mouse striatum became small neuronal grafts, or large grafts with cell types from all germ layers independent of their ES cell genotype. This demonstrates that Smad4-/- and Cripto-/- ES cells favor a neural fate in vitro, but also express the mesodermal phenotype, implying that deletion of either Smad4 or Cripto is not sufficient to block nonneuronal tissue formation.

Animals↗

Growth factor regulation of lens development.

Lens arises from ectoderm situated next to the optic vesicles. By thickening and invaginating, the ectoderm forms the lens vesicle. Growth factors are key regulators of cell fate and behavior. Current evidence indicates that FGFs and BMPs are required to induce lens differentiation from ectoderm. In the lens vesicle, posterior cells elongate to form the primary fibers whereas anterior cells differentiate into epithelial cells. The divergent fates of these embryonic cells give the lens its distinctive polarity. There is now compelling evidence that, at least in mammals, FGF is required to initiate fiber differentiation and that progression of this complex process depends on the synchronized and integrated action of a number of distinct growth factor-induced signaling pathways. It is also proposed that an antero-posterior gradient of FGF stimulation in the mammalian eye ensures that the lens attains and maintains its polarity and growth patterns. Less is known about differentiation of the lens epithelium; however, recent studies point to a role for Wnt signaling. Multiple Wnts and their receptors are expressed in the lens epithelium, and mice with impaired Wnt signaling have a deficient epithelium. Recent studies also indicate that other families of molecules, that can modulate growth factor signaling, have a role in regulating the ordered growth and differentiation of the lens.

Animals↗

Transforming growth factor-beta superfamily members expressed in rat incisor pulp.

The transforming growth factor (TGF)-beta superfamily comprises more than 35 structurally related genes that have been implicated in embryonic induction and morphogenesis. Different superfamily members may have distinct regulatory roles in tooth development and maintenance. Degenerate primer sets derived from the highly conserved carboxy terminal region of the TGF-beta superfamily were used for reverse transcriptase polymerase with poly(A)+ RNA from the rat incisor pulp as a template. TGF-beta superfamily members expressed in the pulp with known potential to differentiate into odontoblasts and to form dentine were identified. Nucleotide-sequence analysis of the amplified cDNAs identified those encoding activin-betaB; bone morphogenic protein (BMP)-2, -4, -7 and -8; growth/differentiation factor (GDF)-1, -5 and -6; and glial cell line-derived neurotrophic factor. In addition, Northern blot analysis detected TGF-beta1 -beta2 and -beta3; activin-betaA; BMP-6 and GDF-7 mRNA transcripts in the pulp. Coordinated expression of TGF-beta superfamily members in pulp may be critical in tooth development and repair.

Activins↗

A theory for developmental control by a program encoded in the genome.

A new genetic mechanism is proposed to explain the evident order seen in embryonic development. This theory postulates control DNA, a set of genetic elements activated in a specific sequence, one at a time. With each cell division, control of gene expression passes to the next control unit in the series. The complete series of control units would constitute the encoded (and inherited) development program of an organism.

Animals↗

Mechanical aspects of cardiac development.

Heart development depends on a dynamic interaction between genetic and epigenetic factors. This paper discusses some of the biomechanical processes that help shape the heart in the embryo. First, an overview is given of some of the critical events that occur during cardiac development. Next, mechanics and modeling strategies are discussed for the morphogenetic processes of cardiac tube formation, cardiac looping, myocardial trabeculation, septation, valve formation, and muscle-fiber alignment. Finally, some considerations for future work in this area are listed.

Animals↗

Distinct roles of maf genes during Xenopus lens development.

Lens development provides a good model system for studying cellular and molecular mechanisms underlying embryonic induction and morphogenesis. Members of the large Maf family of transcription factors, L-Maf and c-Maf, have been shown to play key roles in chick and mouse lens development. Here we report identification of two Xenopus maf genes, XmafB and XL-maf, which exhibit unique temporal and spatial expression patterns during lens formation. XmafB can first be detected in the presumptive lens-forming ectoderm, when the primary eye vesicle makes contact with the head ectoderm. XL-maf expression appears a little later, just before thickening of the lens placode, and both XmafB and XL-maf can be detected in the lens placode. During lens vesicle formation, the expression domains of XmafB and XL-maf segregated from each other, resulting in restricted expression in lens epithelial and fiber cells, respectively. When the optic cup anlagen was removed, only XmafB expression is detected. Both Mafs can induce the lens fiber cell-specific markers, betaA4- and gamma-crystallins. In animal cap assays, XmafB can induce Pax6, Xlens1 and Sox3 expression, but XL-maf fails to induce Pax6 and Xlens1 expression. These results suggest that these maf genes are involved in the regulation of cell-type specific gene expression and play roles in inductive events during Xenopus lens development.

Animals↗

Axial specification in higher vertebrates.

The specification of the body axis in the embryo is reflected in the structure of the vertebral column. Expression patterns of Hox genes in the prevertebrae suggest their involvement in this specification process and in the maintenance of vertebral identities. A single, ectopically expressed Hox gene can reprogramme the rostral part of the vertebral column and induce phenotypic alterations interpretable as homeotic transformations.

Animals↗

Pattern formation in the vertebrate nervous system.

In recent years, the classical approaches of experimental embryology have been used in combination with more modern techniques to investigate aspects of neurogenesis. This combination has advanced our knowledge of several areas of neuronal development, including the lineages of neuronal precursors, the segmentation of the nervous system, and the patterning of the neural tube.

Animals↗

Development of the neural crest.

Mutations that affect the morphogenetic behaviour and differentiation of neural crest-derived cells in mouse embryos have been shown to alter genes that code for growth factors or growth factor receptors. Identification of these and other gene products provide opportunities to understand when and how developmentally distinct embryonic cell populations arise, and how interactions between localized developmental cues and responsive cell subpopulations can be modulated during development.

Animals↗

Axon guidance in the vertebrate central nervous system.

The development of connections in the central nervous system depends on the ability of the tips of growing axons to find their appropriate, often distant, target field. Factors that regulate axon outgrowth may be distinct from those that influence direction finding. Tissue culture methods have helped to distinguish between possible in vivo mechanisms and, in some cases, have identified candidate molecules.

Animals↗