Cells & Development

Animal caps are the original organoid!

Fig. 1. Animal cap assay and sandwich method as in vitro induction systems. In amphibians, a blastocoel cavity clearly forms inside the animal hemisphere during the blastula and early gastrula stages. The cap-like portion lining the roof of the blastocoel cavity is the animal cap. This region consists of a sheet of pluripotent cells, organized into one or several layers. In the animal cap assay, the animal cap was treated with a physiological saline solution containing inducing factors and then cultured. Depending on the type, concentration, and duration of exposure to the inducing factors, animal caps can differentiate into various cell types. In contrast, the sandwich method, involves culturing the inducer source in between two animal caps. In this technique, the sources of induction can include the dorsal lip of the blastopore (organizer), adult tissues, pelletized soluble factors, or animal caps pretreated with soluble factors. In this figure, activin is used as an example of an inducing factor.

Fig. 12. Summary of the in vitro induction system using activin as an inducing factor. This in vitro induction system utilizes activin and retinoic acid as inducing factors to treat animal caps, employing techniques such as animal cap assay, dissociation/reaggregation protocol, and the sandwich method. By applying these methods, various levels of self-organization can be replicated and controlled in vitro, ranging from lower-order cell differentiation to higher-order tissue differentiation, organogenesis, and even the formation of fundamental body plans. Abbreviations: Dorsal [D], ventral [V], and retinoic acid [RA].

Fig. 11. Formation of embryoids by artificial activin concentration gradients. To create embryoids, animal caps were prepared through treatment with low (0.5–1 ng/ml), intermediate (5–10 ng/ml), or high (50–100 ng/ml) concentrations of activin. These three types of activin-treated animal caps were then sequentially arranged and cultured with untreated animal caps. After 3 days of culture, embryoids with distinct head and trunk-tail structures were formed (A). Histological sections revealed differentiation into head tissues, such as the cement gland [cg] and eyes, and trunk-tail tissues including the ear vesicle [ev], brain [br], notochord [not], muscle [mus], and gut (B). When newt embryos are used in similar combination cultures, neural plate structures forming the brain [white arrow] and axial structures forming the trunk-tail regions [black arrow] are sometimes observed (C).

Fig. 7. In vitro heart formation and in vivo transplantation experiment. When treated with a high concentration of activin, the animal caps of Xenopus embryos did not differentiate into heart tissue. However, if the animal cap dissociates into individual cells before activin treatment and then reaggregates, it forms a beating heart [arrow] with 100 % efficiency (A). This heart expresses differentiation marker genes, such as Nkx2.5, GATA-4, Tbx5, MHCα, TnIc (cardiac troponin I), and ANF, none of which are expressed in an animal cap treated with activin alone, without dissociation/reaggregation (B). Electron microscopy reveals the presence of intercalated discs [id] specific to the cardiac muscle, along with visible mitochondria [m] and Z-bands [z] (C). When the reaggregated heart tissue is orthotopically transplanted into the cardiac primordium of a neurula-stage embryo, it integrates without rejection and continues to beat (D), although it does not persist through host metamorphosis. In contrast, when the reaggregated tissue is ectopically transplanted into the ventral region of the neurula, it begins to beat synchronously with the host heart and gradually reddens as it initiates blood circulation (E).

A fascinating review on the role of Activin in organ induction. Isn't it wild that in Xenopus embryos, a piece of the animal cap can be induced with Activin at different concentrations and buffers to form the ❤️, kidney, the pancreas, head, tail, and even a whole embryoid 🤯:
doi.org/10.1016/j.cd...

A whole embryoid is wild. Check out this review by Makoto Asashima et al.

Fig. 1. Animal cap assay and sandwich method as in vitro induction systems. In amphibians, a blastocoel cavity clearly forms inside the animal hemisphere during the blastula and early gastrula stages. The cap-like portion lining the roof of the blastocoel cavity is the animal cap. This region consists of a sheet of pluripotent cells, organized into one or several layers. In the animal cap assay, the animal cap was treated with a physiological saline solution containing inducing factors and then cultured. Depending on the type, concentration, and duration of exposure to the inducing factors, animal caps can differentiate into various cell types. In contrast, the sandwich method, involves culturing the inducer source in between two animal caps. In this technique, the sources of induction can include the dorsal lip of the blastopore (organizer), adult tissues, pelletized soluble factors, or animal caps pretreated with soluble factors. In this figure, activin is used as an example of an inducing factor.

Fig. 12. Summary of the in vitro induction system using activin as an inducing factor. This in vitro induction system utilizes activin and retinoic acid as inducing factors to treat animal caps, employing techniques such as animal cap assay, dissociation/reaggregation protocol, and the sandwich method. By applying these methods, various levels of self-organization can be replicated and controlled in vitro, ranging from lower-order cell differentiation to higher-order tissue differentiation, organogenesis, and even the formation of fundamental body plans. Abbreviations: Dorsal [D], ventral [V], and retinoic acid [RA].

Fig. 11. Formation of embryoids by artificial activin concentration gradients. To create embryoids, animal caps were prepared through treatment with low (0.5–1 ng/ml), intermediate (5–10 ng/ml), or high (50–100 ng/ml) concentrations of activin. These three types of activin-treated animal caps were then sequentially arranged and cultured with untreated animal caps. After 3 days of culture, embryoids with distinct head and trunk-tail structures were formed (A). Histological sections revealed differentiation into head tissues, such as the cement gland [cg] and eyes, and trunk-tail tissues including the ear vesicle [ev], brain [br], notochord [not], muscle [mus], and gut (B). When newt embryos are used in similar combination cultures, neural plate structures forming the brain [white arrow] and axial structures forming the trunk-tail regions [black arrow] are sometimes observed (C).

Fig. 7. In vitro heart formation and in vivo transplantation experiment. When treated with a high concentration of activin, the animal caps of Xenopus embryos did not differentiate into heart tissue. However, if the animal cap dissociates into individual cells before activin treatment and then reaggregates, it forms a beating heart [arrow] with 100 % efficiency (A). This heart expresses differentiation marker genes, such as Nkx2.5, GATA-4, Tbx5, MHCα, TnIc (cardiac troponin I), and ANF, none of which are expressed in an animal cap treated with activin alone, without dissociation/reaggregation (B). Electron microscopy reveals the presence of intercalated discs [id] specific to the cardiac muscle, along with visible mitochondria [m] and Z-bands [z] (C). When the reaggregated heart tissue is orthotopically transplanted into the cardiac primordium of a neurula-stage embryo, it integrates without rejection and continues to beat (D), although it does not persist through host metamorphosis. In contrast, when the reaggregated tissue is ectopically transplanted into the ventral region of the neurula, it begins to beat synchronously with the host heart and gradually reddens as it initiates blood circulation (E).

A fascinating review on the role of Activin in organ induction. Isn't it wild that in Xenopus embryos, a piece of the animal cap can be induced with Activin at different concentrations and buffers to form the ❤️, kidney, the pancreas, head, tail, and even a whole embryoid 🤯:
doi.org/10.1016/j.cd...

A new paper published in @jcb.org by postdoc Jorge Diaz from the Mayor lab at UCL shows that during collective migration, epithelial-like clusters generate traction force mainly through cryptic protrusions at the centre, while mesenchymal clusters do so at their periphery:
doi.org/10.1083/jcb....

Fig. 1. Embryonic origins of Schwann cell precursors. Transverse cross-section through the neural tube showing three pathways giving rise to Schwann cell precursors (orange) that have been discussed in the literature: 1. Neural crest cells (blue) migrate from the dorsal neural tube and give rise to Schwann cell precursors along the dorsal root along which they migrate into the periphery. 2. Neural crest cells (blue) migrate to the site of the future dorsal root entry zone (DREZ) or future motor exit point (MEP) where they give rise to boundary cap cells (green). These boundary cap cells then give rise to Schwann cell precursors along the dorsal and ventral roots. 3. The neuroepithelium (purple) is a currently contested source of Schwann cell precursors along the ventral and possibly dorsal roots. Arrows show direction of migration. (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.)

Fig. 2. Schwann cell precursor derivatives. Schwann cell precursors (orange) have been shown to give rise to a diverse range of cell types (blue). Grey circles represent axons, viewed in transverse cross-section. Arrows show direction of differentiation. (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.)

Did you know that melanocytes, chondrocytes, and even osteoblasts can be differentiated from Schwann Cell Precursors? These cells don't only give rise to Schwann cells as the name suggests but many other cell types. Check out this interesting review by Marianne Bronner et al: doi.org/10.1016/j.cd...

Congratulations, @rashmi-priya.bsky.social. Rashmi's works focus on the mechanics of heart development using zebrafish as a model system. Fantastic achievement!

Fig. 1. Embryonic origins of Schwann cell precursors. Transverse cross-section through the neural tube showing three pathways giving rise to Schwann cell precursors (orange) that have been discussed in the literature: 1. Neural crest cells (blue) migrate from the dorsal neural tube and give rise to Schwann cell precursors along the dorsal root along which they migrate into the periphery. 2. Neural crest cells (blue) migrate to the site of the future dorsal root entry zone (DREZ) or future motor exit point (MEP) where they give rise to boundary cap cells (green). These boundary cap cells then give rise to Schwann cell precursors along the dorsal and ventral roots. 3. The neuroepithelium (purple) is a currently contested source of Schwann cell precursors along the ventral and possibly dorsal roots. Arrows show direction of migration. (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.)

Fig. 2. Schwann cell precursor derivatives. Schwann cell precursors (orange) have been shown to give rise to a diverse range of cell types (blue). Grey circles represent axons, viewed in transverse cross-section. Arrows show direction of differentiation. (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.)

Did you know that melanocytes, chondrocytes, and even osteoblasts can be differentiated from Schwann Cell Precursors? These cells don't only give rise to Schwann cells as the name suggests but many other cell types. Check out this interesting review by Marianne Bronner et al: doi.org/10.1016/j.cd...

Happy #FluorescenceFriday. Here are some labelled myeloid cells from frog 🐸 embryos migrating inside tissue.
📹: @anhhle2702.bsky.social, postdoc fellow at @ucl-cdb.bsky.social

Fig. 1. IGF2 and Cerberus mRNAs cooperate in ectopic head induction in Xenopus embryos. Embryos were microinjected into the ventral marginal zone of a single blastomere at the 4- to 8-cell stage. (A) Uninjected control sibling at early tailbud stage (n = 81). (B) A single ventral injection of IGF2 mRNA caused a small ectopic head protrusion with a pigmented cement gland on the belly (n = 86, 68 % with ectopic structures). (C) Cerberus mRNA induced a secondary head-like structure (n = 78, 94 % with ectopic heads). (D) Co-injection of IGF2 and Cerberus mRNAs induced a large ectopic head with an expanded cement gland (n = 90, 98 % with ectopic heads). (E–H) Panoramic views of control and injected embryos. Injected mRNA doses per embryo were: Cerberus, 100 pg; IGF2, 2 ng. Results from two experiments. Scale bars are 500 μm (A-D) and 2 mm (E-H).

Fig. 6. Dominant-negative IGF receptor 1 blocked ectopic head formation by Cerberus mRNA in single ventral injections. (A) Control embryo at stage 24 injected with LacZ (100 pg) mRNA but not stained for β-galactosidase (n = 50). (B) DN-IGFR (600 pg) and LacZ injected embryos (n = 20, all normal). (C) Cerberus (100 pg) injected embryos with ectopic heads (n = 56, 96 % ectopic heads). (D) DN-IGFR blocked Cerberus ectopic heads (n = 33, 88 % with no ectopic structures, 12 % with small cement glands). (E–F) LacZ staining for (A–D). Scale bar, 500 μm.

A very curious paper from the De Robertis lab shows how Cerberus - a growth factor that inhibits Wnt signalling, and IGF - a growth factor that activates MAPK signalling, can synergistically induce a new head (aka ectopic archencephalic differentiation) in Xenopus embryos.
doi.org/10.1016/j.cd...

2-head frogs? 😲

Fig. 1. IGF2 and Cerberus mRNAs cooperate in ectopic head induction in Xenopus embryos. Embryos were microinjected into the ventral marginal zone of a single blastomere at the 4- to 8-cell stage. (A) Uninjected control sibling at early tailbud stage (n = 81). (B) A single ventral injection of IGF2 mRNA caused a small ectopic head protrusion with a pigmented cement gland on the belly (n = 86, 68 % with ectopic structures). (C) Cerberus mRNA induced a secondary head-like structure (n = 78, 94 % with ectopic heads). (D) Co-injection of IGF2 and Cerberus mRNAs induced a large ectopic head with an expanded cement gland (n = 90, 98 % with ectopic heads). (E–H) Panoramic views of control and injected embryos. Injected mRNA doses per embryo were: Cerberus, 100 pg; IGF2, 2 ng. Results from two experiments. Scale bars are 500 μm (A-D) and 2 mm (E-H).

Fig. 6. Dominant-negative IGF receptor 1 blocked ectopic head formation by Cerberus mRNA in single ventral injections. (A) Control embryo at stage 24 injected with LacZ (100 pg) mRNA but not stained for β-galactosidase (n = 50). (B) DN-IGFR (600 pg) and LacZ injected embryos (n = 20, all normal). (C) Cerberus (100 pg) injected embryos with ectopic heads (n = 56, 96 % ectopic heads). (D) DN-IGFR blocked Cerberus ectopic heads (n = 33, 88 % with no ectopic structures, 12 % with small cement glands). (E–F) LacZ staining for (A–D). Scale bar, 500 μm.

A very curious paper from the De Robertis lab shows how Cerberus - a growth factor that inhibits Wnt signalling, and IGF - a growth factor that activates MAPK signalling, can synergistically induce a new head (aka ectopic archencephalic differentiation) in Xenopus embryos.
doi.org/10.1016/j.cd...

Looks like a fantastic meeting. Register now.

Ist2 is a #phospholipid scramblase that links #lipid transport at the ER to organelle homeostasis, say Heitor Gobbi Sebinelli, Camille Syska, Hafez Razmazma, Luca Monticelli, Guillaume Lenoir, Alenka Čopič @umontpellier.bsky.social et al: rupress.org/jcb/article/...

#Biophysics #ER_literature

We are looking for a Bioinformatician (both graduate and postdoctoral levels) to join our lab. Please help us spread the word about this opportunity!

Applicants should submit their motivation letter, full CV and academic record to Juan R. Martínez-Morales: jrmarmor@upo.es

Fig. 1. Timeline of organoids development. The history of organoids was initiated by Ross Harrison's origin of nerve fiber experiments and continues to evolve to the present day.

Fig. 2. Timeline of MSCs development. In 1970, Friedenstein first divided “fibroblast colonies” from guinea-pig bone marrow and spleen. In 1976, “clonogenic fibroblast precursor cells” were discovered in mouse bone marrow. In 1995, the first-in-human trial of MSCs was conducted. In 1999, it was first discovered that MSCs can differentiate in vitro into osteoblasts, adipocytes, and chondrocytes. During the period from 2000 to 2010, key functions of MSCs, including homing and migration, were discovered. In 2018, MSCs entered clinical trials for heart failure and Crohn's disease. From 2021 to 2025, clinical trials for MSCs expanded to include cirrhosis, osteoarthritis, and diabetic foot.

Fig. 3. Schematic illustration of MSC-mediated optimization of organoids: from challenges to future perspectives. Current organoid systems face limitations such as lack of vasculature, central necrosis, and absence of functional immune components. MSCs address these challenges through two main strategies: acting as structural components in co-culture systems (direct relations) and serving as microenvironmental regulators via paracrine signaling and EVs (indirect relations). The integration of MSCs leads to improved organoid outcomes, including promoted angiogenesis, enhanced maturation, and immunomodulation. Future directions involve combining MSC-organoid systems with 3D bioprinting and organ-on-a-chip technologies to facilitate disease modeling, drug screening, and clinical translation.

Organoid technology is one of the most significant advancements deriving from developmental biology. Yet, many aspects of the biology of organoid itself remain elusive, one of which is the role of mesenchymal stem cells.
This review:
doi.org/10.1016/j.cd...
by Wang et al discusses this in detail.

Fig. 1. Timeline of organoids development. The history of organoids was initiated by Ross Harrison's origin of nerve fiber experiments and continues to evolve to the present day.

Fig. 2. Timeline of MSCs development. In 1970, Friedenstein first divided “fibroblast colonies” from guinea-pig bone marrow and spleen. In 1976, “clonogenic fibroblast precursor cells” were discovered in mouse bone marrow. In 1995, the first-in-human trial of MSCs was conducted. In 1999, it was first discovered that MSCs can differentiate in vitro into osteoblasts, adipocytes, and chondrocytes. During the period from 2000 to 2010, key functions of MSCs, including homing and migration, were discovered. In 2018, MSCs entered clinical trials for heart failure and Crohn's disease. From 2021 to 2025, clinical trials for MSCs expanded to include cirrhosis, osteoarthritis, and diabetic foot.

Fig. 3. Schematic illustration of MSC-mediated optimization of organoids: from challenges to future perspectives. Current organoid systems face limitations such as lack of vasculature, central necrosis, and absence of functional immune components. MSCs address these challenges through two main strategies: acting as structural components in co-culture systems (direct relations) and serving as microenvironmental regulators via paracrine signaling and EVs (indirect relations). The integration of MSCs leads to improved organoid outcomes, including promoted angiogenesis, enhanced maturation, and immunomodulation. Future directions involve combining MSC-organoid systems with 3D bioprinting and organ-on-a-chip technologies to facilitate disease modeling, drug screening, and clinical translation.

Organoid technology is one of the most significant advancements deriving from developmental biology. Yet, many aspects of the biology of organoid itself remain elusive, one of which is the role of mesenchymal stem cells.
This review:
doi.org/10.1016/j.cd...
by Wang et al discusses this in detail.

An amazing course!
You'll learn: genetic manipulation including CRISPR-Cas9, oragnoid generation, explant systems, biomechanics, high-resolution imaging and analysis, bioinformatics, and more!

Register now!
Deadline: January 16, 2026

Cell & Developmental Biology of Xenopus: Gene Discovery & Disease Cold Spring Harbor Laboratory Meetings & Courses -- a private, non-profit institution with research programs in cancer, neuroscience, plant biology, genomics, bioinformatics.

Modern Xenopus research uses this system to study #devbio, genetic diseases, biomechanics, and cell biology. If you want hands-on experience, register now to the CSHL Cell & Developmental Biology of Xenopus:
Gene Discovery & Disease
meetings.cshl.edu/courses.aspx...
Deadline: January 16, 2026

Thank you for all the engagements. Have a wonderful holiday. We will see you again next year 👋

Thank you for all the engagements. Have a wonderful holiday. We will see you again next year 👋

This is our last post of the year. Hope you have a wonderful holidays. Remember, good science only comes from a well-rested mind. We will see you again next year! #MicroscopyMonday #Christmas
Image: 3D Christmas spheroids
Staining: Phalloidin
Photo credit: Postdoc Hoang Anh Le, @ucl-cdb.bsky.social

✨ Blinking #nanobodies that work for single-molecule localization 🔬
Our new preprint shows that the self-blinking dye JF635b restores robust, buffer-free blinking in #nanobodies, enabling reliable #dSTORM, #MINFLUX, and more, without chemical-switching buffers. Opening new possibilities for #ExM!

Fig. 1. Doble immunodetection of CD68 and F4/80 during ear hole regeneration in early postnatal mice.

Fig. 6. Clodronate liposomes treated ears in re-differentiation show acceleration of cartilage maturation.

Fig. 4. Modifications in the regenerative response by the treatment with clodronate liposomes during wound healing phase of early postnatal mice ear hole regeneration.

Tissue-resident macrophages are doing more than just protecting from infection. In this interesting paper, René Fernando Abarca-Buis et al shows that they can promote reepithelialization and blastema formation and regulate the maturation of chondrocytes. Check it out here:
doi.org/10.1016/j.cd...

Check out the summary written by our Editor in Chief, Professor Roberto Mayor:
www.sciencedirect.com/science/arti...

And if you missed it, here is the link to Part I of the collection:
www.sciencedirect.com/special-issu...

Many small photos taken from the symposium organised to reveal Spemann and Mangold in the background.

We're in love with this cover image! 🧡
Part II of our Special Collection celebrating the Centennial of the Discovery of The Organiser is here. This issue focuses on the work presented at the Centennial Symposium at the University of Freiburg in September 2024:
www.sciencedirect.com/journal/cell...

Check out Part II of our special collection celebrating the centennial of the discovery of the organiser. From classical developmental biology, to tissue mechanics, and organoid and plant development, we've got it all!

❗PREPRINT ALERT❗
doi.org/10.64898/202...
The lab of M. Lisa Manning at @syracuseu.bsky.social in collaboration with Ale Mongera at @ucl-cdb.bsky.social show that in the avian presomitic mesoderm, Contact Inhibition of Locomotion has a tissue-wide effect, making tissue act like a fluid under tension.

Check out the summary written by our Editor in Chief, Professor Roberto Mayor:
www.sciencedirect.com/science/arti...

And if you missed it, here is the link to Part I of the collection:
www.sciencedirect.com/special-issu...

Many small photos taken from the symposium organised to reveal Spemann and Mangold in the background.

We're in love with this cover image! 🧡
Part II of our Special Collection celebrating the Centennial of the Discovery of The Organiser is here. This issue focuses on the work presented at the Centennial Symposium at the University of Freiburg in September 2024:
www.sciencedirect.com/journal/cell...