The evolution of developmental biology through conceptual and technological revolutions

Cell, Journal Year: 2024, Volume and Issue: 187(14), P. 3461 - 3495

Published: June 20, 2024

Developmental biology-the study of the processes by which cells, tissues, and organisms develop change over time-has entered a new golden age. After molecular genetics revolution in 80s 90s diversification field early 21st century, we have phase when powerful technologies provide approaches open unexplored avenues. Progress has been accelerated advances genomics, imaging, engineering, computational biology emerging model systems ranging from tardigrades to organoids. We summarize how revolutionary led remarkable progress understanding animal development. describe classic questions gene regulation, pattern formation, morphogenesis, organogenesis, stem cell are being revisited. discuss connections development with evolution, self-organization, metabolism, time, ecology. speculate developmental might evolve an era synthetic biology, artificial intelligence, human engineering.

Language: Английский

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Hallmarks of regeneration

Cell stem cell, Journal Year: 2024, Volume and Issue: 31(9), P. 1244 - 1261

Published: Aug. 19, 2024

Language: Английский

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Ets21C sustains a pro-regenerative transcriptional program in blastema cells of Drosophila imaginal discs

Current Biology, Journal Year: 2022, Volume and Issue: 32(15), P. 3350 - 3364.e6

Published: July 11, 2022

An important unanswered question in regenerative biology is to what extent regeneration accomplished by the reactivation of gene regulatory networks used during development versus activation regeneration-specific transcriptional programs. Following damage, Drosophila imaginal discs, larval precursors adult structures, can regenerate missing portions localized proliferation damage-adjacent tissue. Using single-cell transcriptomics regenerating wing we have obtained a comprehensive view transcriptome discs and identified two cell populations within blastema, Blastema1 Blastema2. Collectively, these cells upregulate multiple genes encoding secreted proteins that promote including Pvf1, upd3, asperous, Mmp1, maturation delaying factor Ilp8. Expression transcription Ets21C restricted this secretory zone; it not expressed undamaged discs. expression activated JNK/AP-1 pathway, function type 1 coherent feedforward loop with AP-1 sustain downstream genes. Without function, blastema fail maintain number genes, which leads premature differentiation severely compromised regeneration. As dispensable for normal development, observations indicate orchestrates network. We also resembling both Blastema2 scribble tumorous They express Ets21C-dependent network, eliminating reduces growth. Thus, mechanisms be co-opted tumors aberrant

Language: Английский

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The limb dorsoventral axis: Lmx1b's role in development, pathology, evolution, and regeneration

Developmental Dynamics, Journal Year: 2024, Volume and Issue: 253(9), P. 798 - 814

Published: Jan. 30, 2024

Abstract The limb anatomy displays well‐defined dorsal and ventral compartments, housing extensor, flexor muscles, which play a crucial role in facilitating locomotion manipulation. Despite its importance, the study of dorsoventral patterning has been relatively neglected compared to other two axes leaving many questions about genes developmental processes implicated unanswered. This review offers thorough overview current understanding patterning, synthesizing classical literature with recent research. It covers specification fate mesoderm subsequent translation into morphologies—a process directed by transcription factor Lmx1b. We also discuss potential evolution paired appendages delve involvement LMX1B Nail‐Patella syndrome, discussing molecular genetic aspects underlying this condition. Finally, polarity digit tip regeneration, prominent instance multi‐tissue regeneration mammals is considered. anticipate that will renew interest critical function evolutionary adaptations but nonetheless overlooked.

Language: Английский

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Long-range morphogen gradient formation by cell-to-cell signal propagation

Physical Biology, Journal Year: 2022, Volume and Issue: 19(6), P. 066001 - 066001

Published: Aug. 3, 2022

Morphogen gradients are a central concept in developmental biology. Their formation often involves the secretion of morphogens from local source, that spread by diffusion cell field, where molecules eventually get degraded. This implies limits to both time and length scales over which morphogen can form set coefficients degradation rates. Towards goal identifying plausible mechanisms capable extending gradient range, we here use theory explore properties cell-to-cell signaling relay. Inspired millimeter-scalewnt-expression flatworms, consider morphogen-mediated production field. We show such relay generate stable oriented local, morphogen-independent source at boundary. be related an effective result due If produced response is polarized, it further gives rise drift. find long-range relevant times without relying on extreme choices or rates, thus exceeding physiological A hence attractive principle conceptualize slowly diffusing for patterning adult contexts as regeneration tissue turn-over.

Language: Английский

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“Pattern Regulation in Epimorphic Fields”, aka the Polar Coordinate Model

Developmental Biology, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

Language: Английский

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Advancements in Bone Replacement Techniques–Potential Uses After Maxillary and Mandibular Resections Due to Medication-Related Osteonecrosis of the Jaw (MRONJ)

Cells, Journal Year: 2025, Volume and Issue: 14(2), P. 145 - 145

Published: Jan. 20, 2025

Maxillofacial bone defects can have a profound impact on both facial function and aesthetics. While various biomaterial scaffolds shown promise in addressing these challenges, regenerating this region remains complex due to its irregular shape, intricate structure, differing cellular origins compared other bones the human body. Moreover, significant variable mechanical loads placed maxillofacial add further complexity, especially cases of difficult-to-treat medical conditions. This review provides brief overview medication-related osteonecrosis jaw (MRONJ), highlighting medication-induced adverse reactions associated clinical challenges treating condition. The purpose manuscript is emphasize role biotechnology tissue engineering technologies therapy. By using scaffold materials biofactors combination with autologous cells, innovative solutions are explored for repair damaged bones. ongoing search effective that address improve vitro preparation subsequent regeneration critical. primary spotlight current research trends novel approaches area.

Language: Английский

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Zebrafish Fin: Complex Molecular Interactions and Cellular Mechanisms Guiding Regeneration

Cold Spring Harbor Perspectives in Biology, Journal Year: 2021, Volume and Issue: 14(7), P. a040758 - a040758

Published: Oct. 14, 2021

Ivonne Sehring and Gilbert Weidinger Institute of Biochemistry Molecular Biology, Ulm University, Albert-Einstein-Allee 11, 89081 Ulm, Germany Correspondence: Gilbert.Weidinger{at}uni-ulm.de

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In vivoassessment of mechanical properties during axolotl development and regeneration using confocal Brillouin microscopy

Open Biology, Journal Year: 2022, Volume and Issue: 12(6)

Published: June 1, 2022

In processes such as development and regeneration, where large cellular tissue rearrangements occur, cell fate behaviour are strongly influenced by mechanics. While most well-established tools probing mechanical properties require an invasive sample preparation, confocal Brillouin microscopy captures parameters optically with high resolution in a contact-free label-free fashion. this work, we took advantage of tool the transparency highly regenerative axolotl to probe its vivo for first time. We mapped frequency shift developing limbs regenerating digits, studied structures axolotl. detected gradual increase cartilage shift, suggesting decreasing compressibility during both regeneration. Moreover, were able correlate regeneration stage, which was undetected fluorescence imaging. The present work evidences potential unravel changes occurring axolotls, setting basis apply technique growing field epimorphic

Language: Английский

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The axolotl kidney: a novel model to study kidney regeneration

Kidney International, Journal Year: 2023, Volume and Issue: 104(3), P. 599 - 604

Published: June 7, 2023

Chronic kidney disease remains a major public health burden worldwide with no ideal treatment besides dialysis or transplantation.1Mehta R.L. Cerda J. Burdmann E.A. et al.International Society of Nephrology's 0by25 initiative for acute injury (zero preventable deaths by 2025): human rights case nephrology.Lancet. 2015; 385: 2616-2643Abstract Full Text PDF PubMed Scopus (654) Google Scholar,2Naved B.A. Bonventre J.V. Hubbell J.A. al.Kidney repair and regeneration: perspectives the NIDDK (Re)Building Kidney consortium.Kidney Int. 2022; 101: 845-853Abstract (10) Scholar Promoting regeneration is promising strategy to treat patients end-stage renal disease. Mammalian can partially damaged nephrons in condition minor progress irreversible fibrosis severe injury.3Humphreys B.D. Valerius M.T. Kobayashi A. al.Intrinsic epithelial cells after injury.Cell Stem Cell. 2008; 2: 284-291Abstract (696) Scholar,4Kumar S. Liu Pang P. al.Sox9 activation highlights cellular pathway acutely injured mammalian kidney.Cell Rep. 12: 1325-1338Abstract (126) By contrast, axolotl (Ambystoma mexicanum) exhibits remarkable ability regrow multiple body parts, including its entire limbs, tail, ocular tissues, liver, heart, even brain.5Gerber T. Murawala Knapp D. al.Single-cell analysis uncovers convergence cell identities during limb regeneration.Science. 2018; 362eaaq068Crossref (187) Scholar, 6Nowoshilow Schloissnig Fei J.F. al.The genome evolution key tissue formation regulators.Nature. 554: 50-55Crossref (289) 7Wei X. Fu Li H. stereo-seq reveals induced progenitor involved brain 377eabp9444Crossref (14) 8Otsuki L. Tanaka E.M. Positional memory vertebrate century's insights from salamander limb.Cold Spring Harb Perspect In Biol. 14: a040899Crossref (6) 9Lust K. Maynard Gomes analyses telencephalon organization, neurogenesis, 377eabp9262Crossref (5) Scholar,S1 However, little known about injury. this study, we showed that shares structural, molecular, functional similarities kidney. We further regenerate also found many genes development are upregulated at early stage tubule regeneration. The has one pair "pear-shaped" kidneys located on dorsal side cavity, as shown Figure 1a b. Hematoxylin eosin staining (see Supplementary Methods) oval-shaped glomeruli (black dotted circle) middle portion kidney, proximal tubules brush borders distal positioned outside (Figure 1c). nephron composed corpuscle containing glomerulus Bowman's capsule, glomerulotubular junction, tubule, Ultrastructural examination using transmission electron microscopy several neatly arranged microvilli, whereas regular lumen few short microvilli 1d). Transmission normal podocyte body, intact primary foot processes podocytes, secondary slit diaphragm structures 1e). Immunofluorescence results podocin, marker mammal, was highly expressed 1f). Megalin, multifunctional endocytic clearance receptor circulating proteins, costained peanut agglutinin (PNA; 1g). Na-K-2Cl cotransporter 2 (NKCC2), thick ascending loop Henle, specifically connecting 1h). Calbindin, Dolichos Biflorus Agglutinin (DBA; 1i). could filtrate reabsorb small (10,000 40,000 molecular weight) but exclude large (70,000 155,000 fluorescent-labeled dextrans, suggesting functions size-based filtration 1j). These data suggested tubular model established i.p. injection gentamicinS2,S3 Methods, S1). As 2a, massive disorganization occurred 7 days (dpi), numerous basophilic aggregates were formed between 14 dpi. possess faint morphology 30 dpi then enlongated into immature 60 Many regenerated border observed 90 2a). Paller's score damage structure 2c). quantification hematoxylin arising these aggregates, which will form lumens elongate mature 2d). Cell death proliferation events process regeneration/repair Terminal deoxynucleotidyl transferase–mediated dUTP nick end-labeling (TUNEL)–positive present 3 dpi, number TUNEL-positive peaked 5 significantly decreased returned basal level (Supplementary S2A D). percentage 5-ethynyl-2′-deoxyuridine (EdU+) increased gradually EdU+ scattered throughout whole EdU incorporation started emerging some structures. EdU-labeling signal much weaker than indicating proliferating frequently time point S2B, C, E). undergoing drastic To provide comprehensive profile regulatory network transcriptional level, performed total mRNA sequencing (bulk RNA sequencing) both gentamicin group control group. transcriptome expression profiles 2444 2668 downregulated comparing samples S3A). transcriptomic deposited available National Center Biotechnology Information Gene Expression Omnibus accession GSE228583. genes, such Lrp2 Slc12a3, exclusively related function S3B). Ontology enrichment assembled metabolic processes, oxidation-reduction process, fatty acid adenosine triphosphate extracellular matrix organization S3C addition, enriched terms associated cycle, DNA replication, cycle S3E). Several nephrogenesis-related (such Ccnd1, Top2a, Sox9, Bmp7, Wnt4) S3B), confirmed quantitative real-time polymerase chain reaction, Western blot, immunostaining, situ hybridization S4). suggest may contribute glomerular tail i.v. doxorubicin.S4 2e, compared periodic acid–Schiff separated Bowmen's capsules there protein cast accumulated 1 week interstitium thicker weeks injection, more severe. smaller those 4 size similar 8 2f). podocin recovered 2g). 2h i). doxorubicin-induced Our reabsorption S5). systemically characterized it Structurally, basic unit nephron, system. podocyte, types glomeruli, Its barrier epithelium converted greatly increases luminal surface area, increasing efficiency reabsorption. Molecularly, expresses markers (megalin [NKCC2]) proteins (podocin), indicative similarity Functionally, ultrafiltration tubule. Given our findings be an study physiology, pathology, vivo. demonstrated First, gentamicin-induced nephrotoxicity model, months bulk RNA-sequencing upregulation proliferation, remodeling, nephrogenesis.4Kumar Scholar,S3,S5–S11 coordinated gene suppress promote regeneration, ultimately determine whether finale perfect fibrosis. Sox9 Wnt4, suggests evolutionarily conserved.4Kumar Scholar,S7,S12–S14 Later, model. So far, only distinguish undamaged ones based because do not have transgenic lines used trace glomeruli. summary, regenerates first show serve novel organism studying Studies invaluable information understanding mechanism underlying All authors declared competing interests. This work supported Key Research Plan (2017YFA0104602 FZ); Natural Science Foundation China Program (82030022 FFH); Introducing Talents Discipline Universities, 111 (D18005 Guangdong Precision Medicine (2022 Provincial Clinical Disease (2020B1111170013 Development (2019YFE0106700 2021YFA0805000 J-FF); (31970782 92268114 High-Level Hospital Construction Project People's (DFJHBF202103 KJ012021012 J-FF). thank Fang Yang Miaomiao Zhou their assistance microscopy. Professor Youhua Haining Zhu discussions project. FZ FFH conceptualized paper. LC, JL, MK, YO, JD, XH, SG experiments validated study. FZ, formal analysis. investigated. J-FF provided resources. curated data. LC wrote original draft visualized reviewed edited. J-FF, supervised. project administration acquired funding. Download .docx (18.23 MB) Help docx files File (Word) Methods. S1. Establishment (AKI) injecting different doses gentamicin. (A) Experimental scheme optimization concentration. (B) (HE) slightly dilated 200 μg/g. 500 μg/g (one black asterisk). Cellular debris (2 asterisks) mg/g. Bars = 100 μm. (C) Detection injected 10-kDa dextran any S2. apoptosis (TUNEL) points counterstained PNA (green). peak detected (dpi). apoptotic 50 rhodamine B isothiocyanate (RITC)–dextran before label all tubules. tubular-like (white circles) 21 (D) Quantification TUNEL+ (E) EdUpositive Data presented mean ± SD. ∗P < 0.05, ∗∗P 0.01, ∗∗∗P 0.001. individual replicates, 6 replicates. NS, significance. S3. regulation Volcano plot differentially Heat map showing versus (C–E) (GO) biological processes. GO (ATP) process. S4. Validation Wnt components SOX9 regenerating kidneys. Quantitative relative CCND1, TOP2A, BMP7 levels reaction (RT-qPCR). Representative blot images WNT4 micrographs double immunostaining (red) active β-catenin Higher-magnification rectangles (bottom). 25 (F) (G) (H) S5. Schematic diagram function. Functional white circles indicated glomerulus, arrowheads 150-kDa fluorescein (FITC)–dextran accumulation. Nuclei stained 4′,6-diamidino-2-phenylindole (DAPI) (blue). shown. References.

Language: Английский

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