Developmental Biology

Phenotypic landscape of the velocity of the TS reaction (the rate-limiting step in DNA synthesis) as a function of activity of MTHFR and GNMT. A, wild-type conditions. Yellow sphere indicated wild-type; white spheres are mutations that lower the activity of the enzymes to 70 % and 35 % of wild-type. B, vitamin B12 deficiency (which lowers the activity of MS). A B12 deficiency destabilizes the TS reaction and the effects of mutations that increase TS activity are enhanced. (GNMT, glycine-N-methyltransferase; MTHFR, methylenetetrahydrofolate reductase; TS, thymidylate synthase).

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Cryptic genetic variation can be revealed by mutations or environmental factors that destabilize homeostatic mechanisms, producing phenotypic variants as a substrate for selection

By H. Frederik Nijhout

tinyurl.com/4dww8f3h
#SpecialIssue in research that transformed #DevBio

Elizabeth Hay's groundbreaking observations on amphibian limb regeneration

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How Betty Hay's findings significantly advanced the fields of cell plasticity and regenerative biology

by Alejandra Beltrán-Rivera, José García-Arrarás
tinyurl.com/55nhr4uv

#SpecialIssue on research that transformed #DevBio

Schematic of a developing avian hindlimb, highlighting the interdigital area (orange), digital ray (green), and avascular mesenchyme (AVM, white). Zoom in 1: "In communication to distal and proximal elements", show the tip of the digital ray (PFR)sending unknown signals to the apical ectodermal ridge (AER, yellow), which in turn communicated back with Fgf8 signal. These signals accumulate in the AVM. Zoom in 2: "Progenitor to the digits", the signals from the AER pass through the AVM into the PFR. Zoom in 3: "Joint patterning/specification", the signals induce a new phalanx segment.

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Fate mapping approaches and scRNA-seq uncover how the avascular mesenchyme is critical to the normal outgrowth and patterning of digits

By C Batho-Samblas, J Smith, L Keavey, N Clancy, L McTeir, and MG Davey

tinyurl.com/2t6dau56

#SpecialIssue in #Avian Model Systems

Apc-cIN mutants show failure of apical constriction and altered actin organization at elevation stages.

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Canonical Wnt pathway modulation is required to correctly execute multiple independent cellular dynamic programs during cranial neural tube closure

by Amber Bogart, Eric Brooks
www.sciencedirect.com/science/arti...

Developed pipeline for optogene expression, activation and imaging in chicken embryos

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Application of the Magnet-Cre optogenetic system in the chicken model

by Michael Pfann, Yuval Cinnamon et al

www.sciencedirect.com/science/arti...

Immunohistochemical analysis of the expression of Sox2 in the facial prominences of mouse embryos

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Identification of the dysregulated let-7c-Sox2 network in the facial prominences of mouse embryos with early retinoid acid exposure

by Chao Song, Yi Zou, et al
www.sciencedirect.com/science/arti...

Subdivision of the neural plate border and gene expression. A. At HH5/6 the neural plate border (pink) surrounds the anterior neural plate (grey). B. Overlapping gene expression at the neural plate border at the level of the dotted line in A. Details are described in the text. C. Gene expression along the anterior-posterior axis of the neural plate border at a stage shown in A. Note: all genes except for Pax6 are also expressed in the neural plate at the same rostro-caudal levels. D. At HH8-9 Pax6 (orange) is expressed anteriorly encompassing olfactory and lens precursors, Pax3 labels the ophthalmic portion of the trigeminal placode and Pax2 marks otic-epibranchial progenitors. Neural crest cell markers are concentrated in the neural folds (green). E. Nested gene expression domains in the placode territory at the stage shown in D. F. At HH10, the placode domains are largely distinct, although cells are still recruited into these domains. Epibranchial placodes have not yet separated. Neural crest cells have begun to migrate anteriorly but are mostly still within the neural tube in more posterior regions.

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Recent studies shaped the current view that the neural plate border is a transient region of multipotent progenitors that co-express competing gene modules and remain fate-undecided until early somite stages

By Andrea Streit

tinyurl.com/3h3k8vkv

#SpecialIssue in #Avian Model Systems

Schematic of Drosophila development from embryo (before stage 6 and after stage 14), to larva, to adult, following the germ cells expressing Ovo over time. Maternal Ovo protein in green; piRNA synthesis genes (sub, chi, Boot, tej) and piRNAs in pink; Transposon expression in yellow, inhibited by piRNA.

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Maternal ovo represses the expression of transposable elements in Drosophila adult ovaries, likely via piRNA synthesis.

By Makoto Hayashi, Yuica Koga, Yasuhiro Kozono, Satoru Kobayashi

tinyurl.com/2azdw4z4

A. Schematic of imaging experiment, with drawings of zebrafish larvae at 3dpf and 7dpf underneath a timeline of imaging every 8 hours. B. (Top) Heatmap of Erk activity at single cell resolution; (Bottom) Raw images of Erk-KTR-mCerulean signal. Scale bar: 100 μm.

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A new powerful live imaging platform tracks Erk signalling dynamics in developing zebrafish hepatocytes at single-cell resolution.

By Faraz Ahmed Butt, Alessandro De Simone, Stefano Di Talia, Kenneth Poss

tinyurl.com/ve5vzp6c

HH14-16 chick neural tubes were electroporated in ovo with constructs expressing MYC-tagged vectors: control empty vector (A, A′), ASCL1 (B, B′), ASCL1NR−AQ (C, C′), ASCL1E−G (D, D′), ASCL1N−A (E, E′), ASCL1R−Q (F, F′), or ASCL1E−G/NR−AQ (G, G′), and harvested 24 h later (HH23-24). A cartoon of a chick embryo and a transverse section of the neural tube is shown in the top middle, with the boxed region representing that imaged in A-G’ (+ is the electroporated side). (A-G′) Immunofluorescence with anti-MYC antibody indicating transgene expression in the electroporated cells (red). BrdU incorporation was used to detect proliferating cells (A-G, green), and RBFOX3 identifies differentiating neurons (A′-G′, green). (H–I) The percentage of electroporated cells (red) co-expressing BrdU (H) and RBFOX3 (I) is shown. ASCL1 induces cells to move laterally out of the ventricular zone, express the neuronal marker RBFOX3, and exit the cell cycle. Black asterisks indicate those cases significantly different from wild-type ASCL1 overexpression. Red asterisks highlight the mutants that decrease co-expression with RBFOX3 relative to control (I). Each data point represents a biological replicate, and the error bars are SEM around the mean, unpaired t-test, ∗∗p 0.001, ∗p 0.01, ns = not significant.

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Distinct functional domains of ASCL1 uniquely control neuronal differentiation and subtype identity, revealing the structural code behind neural fate decisions.

By Yuji Nakada, Madison Martinez, and Jane Johnson

tinyurl.com/3b6b325m

Shroom3 is required within the neural retina during optic fissure closure

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Shroom3 facilitates optic fissure closure via tissue alignment and reestablishment of apical-basal polarity during epithelial fusion

by Jessica Herstine, Jordyn Mensh, Timothy Plageman Jr. et al
www.sciencedirect.com/science/arti...

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Teaching developmental biology through a biocultural lens can challenge biological essentialism and build a more equitable science

By Julia Paxson
tinyurl.com/43htbxfx

#SpecialIssue in Teaching #DevBio for Social Change

Diagram centre around central text "Teaching Developmental Biology in a Social Context". Scientific background is in red, ethical considerations in green, societal consideration in blue. From the top right quadrant, clockwise: Red: Drawing of an embryo, DNA molecule, microscope, and book; "Fetal viability". Red: Diagram of early development from fertilisation to early embryo; "Modern and traditional developmental stages". Blue: "Legal stance", "Cultural differences", Religion; drawing of the scales of justice, a world map, and the symbols of three Abrahamic religions. Red: "Assisted reproductive technology: in vitro fertilisation, cryopreservation, pre-implantation genetic testing, gene therapy"; diagram of a uterus and egg during IVF. Green: "Ethics: Deontological, utilitarian". Green: "Inequalities within and among countries; parental decision making; health care services; human rights; morals".

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Multidisciplinary educational approach to reproductive technology links developmental biology, ethics, and law to prepare biologists for real-world controversies

By J Azzi, Z Wehbi, P Hussein Kobeissy, R Kerek
tinyurl.com/2xvm64ue

#SpecialIssue in Teaching #DevBio for Social Change

Yellowed and aged book cover: "Für Darwin Von Fritz Müller / Mit 67 Figuren in Holzschnitt / Leipzig, Verlag von Wilhelm Engelmann 1864" Source: Wellcome Collection.

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Fritz Müller’s "Für Darwin" (1864) bridged evolution and development, anticipating evo-devo and warning to the dangers of scientific dogma

By Scott Gilbert and Beatrice Steinert
tinyurl.com/3sccvcr5

#SpecialIssue on Research that transformed #DevBio

Ways in which social structures can impact human life history.

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Developmental life history transitions can be shaped by structural inequities: Insights from the sociology of race

by Sarah McMenamin, Latrica Best

sciencedirect.com/science/arti...

Wholemount images of Zebrafish embryos following treatment with either DMSO (A-P) or Thalidomide (A′-P′) at 6hpf and fixed 24h and stained by in-situ hybridisation for crbn, ddb1, cul4A and ikzf1. No differences between DMSO and thalidomide treated embryos was observed. Arrowheads indicate where expression is present in controls and unchanged in thalidomide treated embryos. Note tail twisting in thalidomide treated embryos in A′, B′, C′, D’. Scale bars: 500 μm.

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Cereblon E3 ligase complex genes are expressed in tissues sensitive to thalidomide in chicken and zebrafish embryos but are unchanged following thalidomide exposure

By LR Fraga, J Reeves, C Mahony, L Erskine, N Vargesson
tinyurl.com/2fx6pbay

#SpecialIssue in Avian Model Systems

Diagram showing he differences between a healthy female bird bone with medullary bone and a pathological bird bone with avian osteoporosis. For each there is a global scan of tibiotarsi whole bone in lateral view, a micro-CT 3D cube reconstruction, and microCT cubes highlighting osteocyte lacunae. In between a box with writing "Differences include: Structural anisotropy, Connectivity density, Trabecular thickness, Osteocyte lacunae orientation".

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Micro-CT 3D structures provide new criteria which can be used to identify medullary bone and female individuals in the avian fossil record.

By Crane AH, Baldry CJ, Rankin KE, Clarkin CE, Williams KA, Gostling NJ.

tinyurl.com/pw5s23js

#SpecialIssue on Avian model systems

A conceptual diagram illustrating tissue patterning during the development and regeneration of a prototypical amniote skin. Complex tissue patterns are established through De novo patterning and multiple steps in adaptive patterning. Regulatory patterning refers to the modifications of appendage phenotypes in adults to adapt to environmental changes. Regenerative patterning describes the reformation of tissue patterns after loss, as observed in wound regeneration or organoid morphogenesis of dissociated progenitor cells.

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This review paper elucidates the organizational principles underlying the integument.

By Chuong, C. M., Wu, P., Yu, Z., Liang, Y. C., & Widelitz, R. B.
doi.org/10.1016/j.yd...

“Scales” in mammals, birds and reptiles: Not all scales are equal.

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Cyclic renewal in three ectodermal appendage follicles: Hairs, feathers and teeth

by Ping Wu et al

www.sciencedirect.com/science/arti...

Novel CREs Int-2C and Ex1up-lacZ show activity in all the Grh-expressing NSCs at the late L3 stage. Scale bars are 50µm.

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Drosophila grh relies on multiple enhancers for robust expression in neural stem cells, with different combinations playing a critical role in regulating its expression in subsets of these cells

By R Sipani, Y Rawal, J Barman, P Abbur, V Kurlawala, & R Joshi
tinyurl.com/2aufrc2w

The posterior ventral aorta domain is expanded in late RA-deficient embryos

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Retinoic acid promotes second heart field addition & regulates ventral aorta patterning in zebrafish.

-by Austin Griffin, Allison Small, Jennifer Schumacher, et al
www.sciencedirect.com/science/arti...

Wnt3a is required to regulate Wolffian duct cell polarity. a–h. Immunofluorescent staining of apical markers, aPKC and the Golgi apparatus (GM130), in the WT and Wnt3a-knockout mice at E9.5. The WT mice exhibited apical distribution of aPKC and GM130. In Wnt3a-knockout embryos, the Wolffian ducts exhibited heterogeneous distributions of aPKC and GM130; although apical polarity was present, it was disrupted (c, d). Both basolateral and luminal apical polarities were detected (e, f, arrows). Excessive accumulation of aPKC was detected (g, h). aPKC was distributed on both the luminal and lateral sides. Medial, left; Lateral, right. i. Rader chart of aPKC dot distribution. The angles and distances from the apical pole (cyan spots in b, d, and h) were measured in the WT and Wnt3a-knockout mice. Bifurcated ducts (f) were excluded from this analysis. j. Average distance of aPKC from the apical pole. Wnt3a-knockout embryos exhibited a dispersed aPKC distribution. k. aPKC signal intensity in the luminal and lateral area. Total signal intensity was normalized to 100 %. aPKC signal was reduced in the luminal area and elevated in the lateral area in the Wnt3a-knockout embryos. Control (Wnt3a+/+ and Wnt3a+/−), n = 6, Wnt3a−/−, n = 6 in i-k. ∗p < 0.05 (Welch’s t-tests). l-s. Laminin and E-cadherin staining of the Wolffian ducts of control and Wnt3a-knockout embryos. Laminin and E-cadherin were predominantly distributed at the basal and apical poles, respectively. In contrast, the basal laminin structure was disrupted, while apical E-cadherin was absent in the stacked duct region of Wnt3a-knockout embryos. Control (Wnt3a+/+ and Wnt3a+/−), n = 6, Wnt3a−/−, n = 6. Scale bars in a-h and l-s = 20 μm. (For interpretation of the references to colour in this figure legend, the reader is referred to the Web version of this article.)

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Wnt3a plays an important role in Wolffian duct development by regulating apicobasal polarity.

By Hayashi, S., Suzuki, H., Takada, S., & Takemoto, T.
doi.org/10.1016/j.yd...

B. germanica capicua (cic): Expression and localization

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The transcription factor Capicua maintains the oocyte polarity in the panoistic ovary of the German cockroach

"Cic interacts with Notch and EGFR pathways"

by Nashwa Elshaer, Jorge Escudero, Maria-Dolors Piulachs
www.sciencedirect.com/science/arti...

Upper panel: The descending decussating neurons (ddNs) of a Ciona larva at 19.5 h post-fertilization (hpf at 20 ◦C, ~ Hotta stage 29) labeled by expression of elecroporated Dmbx/Defcab >Unc-76::YFP reporter plasmid. Scale bar =10 μm. Right: comparative diagrams of ddNs and their putative vertebrate homologs, the Mauthner cells (species depicted as an example is Danio rerio). Lower panel: A summary diagram of a ddN gene regulatory network. Diagram for a ddN-specific gene regulatory network downstream of Pax3/7. Some branches are shared with different neuron types, such as ACINs, epidermal neurons, or papilla neurons (a sub-type of epidermal neurons). Dashed arrow indicates regulatory connection supported by RNAseq data, but not validated by reporter plasmids or in situ mRNA hybridization. Grey arrow indicates possible role of Lhx1/5 in regulating maintenance, but not initial activation of Dmbx and Defcab.

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Scientists have identified a provisional regulatory circuit downstream of the transcription factor Pax3/7 operating in the descending decussating neurons (ddNs) of the tunicate Ciona robusta.

By Kim, K., Piekarz, K. M., & Stolfi, A.
doi.org/10.1016/j.yd...

Sea star embryo development. Blimp1 mRNA expression localizes at the oocyte's vegetal site, similar to Vasa and Wnt, important genes for germline formation.

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mRNA splicing variants of the transcription factor Blimp1 differentially regulate germline genes in echinoderms

"Each Blimp1 isoform has distinct functions within & between species"

by Gerardo Reyes, Nathalie Oulhen, Gary Wessel
www.sciencedirect.com/science/arti...

The author Dave Sherwood with the chicken flock that he and his wife Nina tend to in their yard in North Carolina.

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David Sherwood draws a powerful parallel between morphogenesis and a scientific career, showing how becoming a biologist is a continual process of shaping, adaptation, and growth. Like development, a scientific life unfolds through adaptation and emergence.

tinyurl.com/6yd46wcx

Feather Morphogenesis

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Feather Morphogenesis

Keratinization and cornification of avian skin appendages during development. Insights from immunolabeling and electron microscopic studies

by Lorenzo Alibardi
www.sciencedirect.com/science/arti...

Experiments highlighting importance of the apical ectodermal ridge (AER) and FGF in proximal-distal limb development. A) Histological section through the tip of chick limb bud showing the prominent ridge of ectoderm (AER; from Saunders, 1948). B, C) RNA in situ hybridization of mouse limb buds showing expression of Fgf4 and Fgf8 in the AER (Niswander unpublished). D) Limb truncations due to excision of the entire AER from chick limb buds at successively later stages (from Saunders, 1948). E) Skeletal stainings of chick embryo limbs: normal (left); truncation due to AER removal (middle); and rescue of proximal-distal growth and patterning by FGF microbeads placed at the limb tip following AER removal (right, from Niswander et al., 1993). Note that chick wing digits were conventionally labeled as digits 2, 3 and 4 but now are denoted as digits 1, 2 and 3. F) Skeletal stainings of mouse embryos: wildtype (left) and after genetic knock-out of Fgf4 and Fgf8 in the AER (right, from Sun et al., 2002). Figures reproduced with journal permission.

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Building a genetic map of limb development driven by the apical ectodermal ridge

By Lee Niswander

tinyurl.com/bdzrjsyz

#SpecialIssue on Research that Transformed #DevelopmentalBiology

Summary of key aspects of the ABC model of flower development A. Illustration of the four floral organs arranged in four concentric whorls (left) based on the Arabidopsis flower (right). B. The basic tenets of the ABC model. The A, B, C genes function in three domains colored differently. Each domain consists of two adjacent whorls. The mutual repression between A and C is shown by a horizontal bar. C. An abc triple mutant flower of Arabidopsis, with no visible petals. D. In situ hybridization to show the expression domains of the A, B, and C genes. Number indicates stages; S (sepal), St (Stamen), and C (carpel) indicate primordia of different floral organ type.

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How homeotic mutants shaped the ABC model, transforming our understanding of floral patterning

By Zhongchi Liu

tinyurl.com/2tc58fbs

#SpecialIssue on Research that Transformed #DevelopmentalBiology

A schematic timeline of the major discoveries in evolution, genetics, and development. In order: "Charles Darwin The origin of species'"; drawing of four Galapagos finches. 1860 "Gregor Mendel 'Genetic Principles'"; drawing of yellow and green peas. 1900; "Mendel Rediscovery"; a black and white photograph of Gregor Mendel. "Morgan 'Chromosome theory'"; drawing of a blue chromosome with four highlights genes. 1920 "Gluecksohn-Waelsch 'mouse genetics'"; a photograph of a brown mouse. 1950 "Ed Lewis 'bithorax mutants'"; drawing of a Drosophila with two pairs of wings. "Walther Gehring 'Antennapedia mutants'"; a photograph of a Drosophila head with legs instead of antennae. 1980; "Heidelberg Mutant Screen"; a picture of a Drosophila embryo. "Homeobox"; a 3D prediction model of a DNA double-helix interacting with protein alpha-helixes.

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From peas to animal embryogenesis: how pioneering work in genetics shaped our understanding of development

By Abraham Fainsod and Martin Blum

tinyurl.com/5n8h423x

#SpecialIssue on Research that Transformed #DevelopmentalBiology