A Yap-dependent mechanoregulatory program sustains cell migration for embryo axis assembly.

The assembly of the embryo's primary axis is a fundamental landmark for the establishment of the vertebrate body plan. Although the morphogenetic movements directing cell convergence towards the midline have been described extensively, little is known on how gastrulating cells interpret mechanical cues. Yap proteins are well-known transcriptional mechanotransducers, yet their role in gastrulation remains elusive.

Regulation of Nodal signaling propagation by receptor interactions and positive feedback.

During vertebrate embryogenesis, the germ layers are patterned by secreted Nodal signals. In the classical model, Nodals elicit signaling by binding to a complex comprising Type I/II Activin receptors (Acvr) and the co-receptor Tdgf1. However, it is currently unclear whether receptor binding can also affect the distribution of Nodals themselves through the embryo, and it is unknown which of the putative Acvr paralogs mediate Nodal signaling in zebrafish.

CTCF knockout in zebrafish induces alterations in regulatory landscapes and developmental gene expression.

Coordinated chromatin interactions between enhancers and promoters are critical for gene regulation. The architectural protein CTCF mediates chromatin looping and is enriched at the boundaries of topologically associating domains (TADs), which are sub-megabase chromatin structures. In vitro CTCF depletion leads to a loss of TADs but has only limited effects over gene expression, challenging the concept that CTCF-mediated chromatin structures are a fundamental requirement for gene regulation.

Analysis of gene network bifurcation during optic cup morphogenesis in zebrafish.

Sight depends on the tight cooperation between photoreceptors and pigmented cells, which derive from common progenitors through the bifurcation of a single gene regulatory network into the neural retina (NR) and retinal-pigmented epithelium (RPE) programs. Although genetic studies have identified upstream nodes controlling these networks, their regulatory logic remains poorly investigated. Here, we characterize transcriptome dynamics and chromatin accessibility in segregating NR/RPE populations in zebrafish.

Patterning the Vertebrate Retina with Morphogenetic Signaling Pathways.

The primordium of the vertebrate eye is composed of a pseudostratified and apparently homogeneous neuroepithelium, which folds inward to generate a bilayered optic cup. During these early morphogenetic events, the optic vesicle is patterned along three different axes-proximo-distal, dorso-ventral, and naso-temporal-and three major domains: the neural retina, the retinal pigment epithelium (RPE), and the optic stalk. These fundamental steps that enable the subsequent development of a functional eye, entail the precise coordination among genetic programs.

, a divergent Yap/Taz family member, cooperates with in survival and morphogenesis via common transcriptional targets.

Yap1/Taz are well-known Hippo effectors triggering complex transcriptional programs controlling growth, survival and cancer progression. Here, we describe , a new Yap1Taz family member with a unique transcriptional activation domain that cannot be phosphorylated by Src/Yes kinases. We show that evolved specifically in euteleosts (i.

Scale-invariant patterning by size-dependent inhibition of Nodal signalling.

Individuals can vary substantially in size, but the proportions of their body plans are often maintained. We generated smaller zebrafish by removing 30% of their cells at the blastula stages and found that these embryos developed into normally patterned individuals. Strikingly, the proportions of all germ layers adjusted to the new embryo size within 2 hours after cell removal.

Immunohistochemistry on Paraffin-Embedded Planarian Tissue Sections.

Planarians are flatworms with almost unlimited regenerative abilities, which make them an excellent model for stem cell-based regeneration. To study the process of regeneration at the cellular level, immunohistochemical staining methods are an important tool, and the availability of such protocols is one of the prerequisites for mechanistic experiments in any animal model. Here, we detail protocols for paraffin embedding and immunostaining of paraffin sections of the model species Schmidtea mediterranea.

JNK controls the onset of mitosis in planarian stem cells and triggers apoptotic cell death required for regeneration and remodeling.

Regeneration of lost tissues depends on the precise interpretation of molecular signals that control and coordinate the onset of proliferation, cellular differentiation and cell death. However, the nature of those molecular signals and the mechanisms that integrate the cellular responses remain largely unknown. The planarian flatworm is a unique model in which regeneration and tissue renewal can be comprehensively studied in vivo.

Wnt signaling in planarians: new answers to old questions.

Wnts are secreted glycoproteins involved in a broad range of essential cell functions, including proliferation, migration and cell-fate determination. Recent years have seen substantial research effort invested in elucidating the role of the Wnt signaling pathway in planarians, flatworms with incredible regenerative capacities. In this review, we summarize current knowledge on the role of canonical (β-catenin-dependent) and non-canonical (β-catenin-independent) Wnt signaling in planarians, not only during regeneration, but also during normal homeostasis.

Early planarian brain regeneration is independent of blastema polarity mediated by the Wnt/β-catenin pathway.

Analysis of anteroposterior (AP) axis specification in regenerating planarian flatworms has shown that Wnt/β-catenin signaling is required for posterior specification and that the FGF-like receptor molecule nou-darake (ndk) may be involved in restricting brain regeneration to anterior regions. The relationship between re-establishment of AP identity and correct morphogenesis of the brain is, however, still poorly understood. Here we report the characterization of two axin paralogs in the planarian Schmidtea mediterranea.

Dishevelled is essential for neural connectivity and planar cell polarity in planarians.

The Wingless/Integrated (Wnt) signaling pathway controls multiple events during development and homeostasis. It comprises multiple branches, mainly classified according to their dependence on β-catenin activation. The Wnt/β-catenin branch is essential for the establishment of the embryonic anteroposterior (AP) body axis throughout the phylogenetic tree.