Developmental biology最新文献

{"title":"WNT4 deficiency impacts heart, diaphragm, and palate development: Insights from human genetics, machine learning, and mouse models","authors":"Andrés Hernández-García ,&nbsp;Bum Jun Kim ,&nbsp;David Chitayat ,&nbsp;Patrick Shannon ,&nbsp;Stephanie Hedges ,&nbsp;Maria Al Bandari ,&nbsp;Maria J. Guillen Sacoto ,&nbsp;Emily Anne Bates ,&nbsp;Yunus H. Ozekin ,&nbsp;Victor Faundes ,&nbsp;Pamela N. Luna ,&nbsp;Chad A. Shaw ,&nbsp;Tara L. Rasmussen ,&nbsp;Chih-Wei Hsu ,&nbsp;Daryl A. Scott","doi":"10.1016/j.ydbio.2025.09.016","DOIUrl":"10.1016/j.ydbio.2025.09.016","url":null,"abstract":"<div><div>WNT4 is a secreted protein that plays a critical role in the regulation of cell fate and embryogenesis. Biallelic variants in <em>WNT4</em> have been linked to SERKAL syndrome, an autosomal recessive disorder characterized by 46,XX sex reversal and dysgenesis of the kidneys, adrenals, and lungs. SERKAL syndrome has only been described in a single consanguineous kindred with four affected fetuses. Additional features seen in a subset of affected fetuses included ventricular septal defect (VSD), congenital diaphragmatic hernia (CDH), and orofacial clefting (OFC). To determine if these additional features were likely to be caused by WNT4 deficiency, we used machine learning to compare <em>WNT4</em> to genes known to cause VSD, CDH, and OFC. When compared to all RefSeq genes, WNT4's rank annotation scores for these congenital anomalies were 94%, 99%, and 98.5%, respectively, indicating a high level of similarity. We subsequently identified a second consanguineous family with SERKAL syndrome in which an affected fetus had CDH and an affected child had OFC. We then demonstrated that a subset of <em>Wnt4</em> null embryos have perimembranous VSDs, anterior and posterior sac CDH, and soft palate clefts. These findings suggest that WNT4 deficiency can cause VSD, CDH, and palatal anomalies in mice and humans with SERKAL syndrome. These studies also suggest that our machine learning approach can be used as a candidate gene prioritization tool, and that targeted mouse phenotyping can serve as a means of confirming the roles of candidate genes in mammalian development.</div></div>","PeriodicalId":11070,"journal":{"name":"Developmental biology","volume":"529 ","pages":"Pages 66-80"},"PeriodicalIF":2.1,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145136991","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Involvement of Tead4, an effector of Hippo signaling, in intestinal remodeling during Xenopus laevis metamorphosis","authors":"Takayuki Iwaki ,&nbsp;Tsuguhide Shimodaira ,&nbsp;Yuki Shibata ,&nbsp;Kenta Fujimoto ,&nbsp;Tomoaki Nakada ,&nbsp;Takashi Hasebe","doi":"10.1016/j.ydbio.2025.10.018","DOIUrl":"10.1016/j.ydbio.2025.10.018","url":null,"abstract":"<div><div>During amphibian metamorphosis, the intestine is remodeled from larval to adult form. In this study, we investigated the expression and localization of <em>Xenopus laevis</em> Tead4 (a key transcription factor in the Hippo pathway) in the metamorphosing intestine, examined its interaction, and analyzed its phylogenetic relationships. Quantitative RT-PCR revealed that both <em>tead4.L</em> and <em>tead4.S</em> (homeologs) transcripts are expressed throughout natural and thyroid hormone (TH)-induced metamorphosis, with modest but stage-specific changes, indicating sensitivity to TH. Triple hybridization chain reaction RNA-FISH showed that <em>tead4</em> expression is broadly distributed in the intestine, with its signal intensity increasing from the metamorphic climax onward, whereas <em>yap1</em> expression is enriched in the connective and muscle layers. There was a partial overlap between <em>tead4</em> and <em>yap1</em> expression, indicating context-dependent co-regulation, and incomplete co-localization of the expressed proteins, suggesting alternative co-factors. Oocyte co-immunoprecipitation assays demonstrated that both Tead4.L and Tead4.S physically associate with Yap1, supporting their role as Hippo pathway effectors. Phylogenetic analysis placed <em>X. laevis</em> Tead4 homeologs within the TEAD2 clade, indicating that the genes annotated as <em>tead4</em> can more accurately be classified as <em>tead2</em>. These findings demonstrate that Tead4 homeologs function as Yap1 partners and contribute to transcriptional control during amphibian intestinal metamorphosis, highlighting their conserved role as effectors of Hippo signaling.</div></div>","PeriodicalId":11070,"journal":{"name":"Developmental biology","volume":"529 ","pages":"Pages 213-218"},"PeriodicalIF":2.1,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145359649","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molecular basis of variations in facial soft tissues: insights from cichlid fishes","authors":"Ehsan Pashay Ahi ,&nbsp;Christian Sturmbauer ,&nbsp;R. Craig Albertson ,&nbsp;Pooja Singh","doi":"10.1016/j.ydbio.2025.10.014","DOIUrl":"10.1016/j.ydbio.2025.10.014","url":null,"abstract":"<div><div>The human face serves as a crucial component of attractiveness and identity, playing a pivotal role in social interactions. Teleost fish models, particularly zebrafish, have offered valuable insights into the developmental and molecular mechanisms governing craniofacial skeletogenesis, owing to the molecular conservation in these processes. However, knowledge regarding the morphogenic processes shaping facial soft tissues remains surprisingly sparse. On the human side, most causal evidence comes from gene–phenotype associations in clinical genetics; however, these studies rarely provide cellular-resolution analyses of facial soft tissues, leaving tissue- and cell-type–specific mechanisms unresolved. The diverse family of Cichlidae constitute ∼10 % of teleost fish species and represent an exceptional opportunity for evolutionary biology research due to their extensive ecological diversity and rapid speciation rates. Cichlid fishes also exhibit remarkable craniofacial morphological diversity, making them excellent models for studying both craniofacial skeletal and soft tissue morphogenesis. Utilizing the wealth of natural mutants within cichlid populations, this short review pitches cichlid fish models as valuable tools for investigating the genetic regulators and interactions underlying facial soft tissue formation. At present, most cichlid studies rely on comparative transcriptomics between closely related species with and without pronounced traits; these data are associative, and the regulatory hierarchy and primary drivers remain to be established through functional tests (e.g., genome editing). By synthesising developmental and regulatory mechanisms that influence morphological variations in facial soft tissues in cichlids and other model organisms, we create a blueprint for future molecular genetic investigations into facial diversity. Accordingly, we highlight the need for (i) causative functional studies in cichlids and (ii) cellular-resolution analyses of human facial soft tissues to bridge correlative and mechanistic evidence across systems.</div></div>","PeriodicalId":11070,"journal":{"name":"Developmental biology","volume":"529 ","pages":"Pages 200-212"},"PeriodicalIF":2.1,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145318338","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Primitive means first, not worst: Critical roles for primitive endoderm in embryos and embryo models","authors":"Marcelio A. Shammami ,&nbsp;Alyssa Virola-Iarussi ,&nbsp;Ian McCrary ,&nbsp;Amy Ralston","doi":"10.1016/j.ydbio.2025.09.008","DOIUrl":"10.1016/j.ydbio.2025.09.008","url":null,"abstract":"<div><div>In mammals, extraembryonic tissues, such as the placenta and yolk sac, are the first cell types to be specified during development because they enable the embryo to take residence and thrive in the uterine environment. Among extraembryonic tissue types, primitive endoderm (PrE), which will eventually contribute to the yolk sac, is especially fascinating. The PrE itself is named for functioning like the embryo's original gut-like tissue. For many years, our understanding of the PrE was limited by the intrinsically challenging nature of accessing and observing this tissue. However, pioneering studies in mouse have gradually revealed that the PrE is more than just nutritive in function. In fact, the PrE lineage gives rise to signaling centers that oversee developmental processes within the fetus – through processes that are very likely conserved between rodents and primates. Thus, understanding the stages between PrE and yolk sac promises clinically relevant models, including stem cell embryo models, which could lead to enhanced success for <em>in vitro</em> fertilization (IVF). Here, we examine the functions of PrE in the context of embryos, stem cells, and embryo models.</div></div>","PeriodicalId":11070,"journal":{"name":"Developmental biology","volume":"528 ","pages":"Pages 255-263"},"PeriodicalIF":2.1,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145124393","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Loss of CMTR1 leads to gastrulation failure and early embryonic lethality","authors":"Janelle M. Welton ,&nbsp;Kimberly D. Tremblay ,&nbsp;Jesse Mager","doi":"10.1016/j.ydbio.2025.08.022","DOIUrl":"10.1016/j.ydbio.2025.08.022","url":null,"abstract":"<div><div>Cap Methyltransferase 1 (CMTR1) facilitates the addition of a 5’ methyl cap on eukaryotic mRNA molecules. Using a knock-out (KO) allele, we demonstrate that CMTR1plays an essential role during gastrulation. In the absence of CMTR1, mutant embryos undergo early lethality, arresting prior to organogenesis with severe developmental delay apparent at E7.5. Multiple molecular approaches indicate significant disruptions in the ability of the CMTR1-KO embryo to form the three primary germ layers – likely driving the observed gastrulation failure. Our analysis of CMTR1 has revealed an unexpected sexually dimorphic phenotype. Female CMTR1 null embryos are more severely delayed and have increased differentially expressed genes compared to male mutants; presumably causing a variety of downstream consequences and a more severe developmental phenotype. Importantly, we do not observe defects in X-inactivation, suggesting that there are unidentified sexually dimorphic mechanisms active during early embryonic stages, prior to the onset of known differences between XX and XY embryos. In sum, we illustrate the necessity of CMTR1 during embryonic development and reveal novel insights into differences in gene regulation pathways between sexes prior to organogenesis.</div></div>","PeriodicalId":11070,"journal":{"name":"Developmental biology","volume":"528 ","pages":"Pages 1-12"},"PeriodicalIF":2.1,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144934086","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The patterning and proliferation roles of Shh are partitioned on distinct exosomes","authors":"Ankita Walvekar ,&nbsp;Shivangi Pandey ,&nbsp;Siddhesh S. Kamat ,&nbsp;Raj K. Ladher ,&nbsp;Neha Vyas","doi":"10.1016/j.ydbio.2025.09.017","DOIUrl":"10.1016/j.ydbio.2025.09.017","url":null,"abstract":"<div><div>Sonic hedgehog (Shh) is a pivotal morphogen in spinal cord development, orchestrating both ventral neural patterning and progenitor proliferation. How these distinct outcomes are specified has remained elusive. Here, we uncover that Shh is secreted via two biochemically and functionally distinct exosomal pools. A dense vesicle fraction, Shh-P150, drives Smoothened–Gli1 signalling to establish ventral progenitor identities, while a lighter pool, Shh-P450, activates a Smoothened–Gαi–dependent pathway that enhances progenitor proliferation without inducing ventral fate. We identify Rab7, a late endosomal regulator, as essential for Shh-P150 biogenesis and for notochord-mediated ventral neural patterning. Loss of Rab7 biases secretion toward the proliferative Shh-P450 pool and disrupts morphogenetic signalling. These findings establish exosomal packaging as a molecular switch that toggles Shh between its mitogenic and morphogenetic roles. By linking exosome biogenesis to developmental outcomes, our work reveals a novel mechanism that safeguards the balance between pattern formation and progenitor expansion during neural tube development, with implications for both developmental disorders and disease contexts where Shh signalling is misregulated.</div></div>","PeriodicalId":11070,"journal":{"name":"Developmental biology","volume":"528 ","pages":"Pages 239-254"},"PeriodicalIF":2.1,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145155730","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Expression and function of new candidate regulators of placodal neurogenesis in Xenopus laevis","authors":"Bertrand Hutlet,&nbsp;Gerhard Schlosser","doi":"10.1016/j.ydbio.2025.08.026","DOIUrl":"10.1016/j.ydbio.2025.08.026","url":null,"abstract":"<div><div>The transcription factor Six1 and its co-activator Eya1 play central and varied roles during the development of sensory neurons derived from the cranial placodes in vertebrates. Previous studies suggested that these proteins promote both the maintenance of proliferative neuronal progenitors and neuronal differentiation. Context-specific interactions of Six1 and/or Eya1 with different cofactors are likely to contribute to the activation of distinct target genes during different stages of placodal neurogenesis. However, while some protein binding partners of Six1 have recently been identified, little is known about Eya1 interaction partners. To uncover additional Eya1 interaction partners with potential roles in placodal neurogenesis, we here conduct a yeast two-hybrid screen in <em>Xenopus laevis</em>. Apart from confirming Six1 (Six1.L) and Six4 (Six4.L and Six4.S) as known protein interaction partners of Eya1, this screen identified 25 additional candidate binding partners including several transcription factors, chromatin modifiers and enzymes involved in posttranslational modifications. Analysis of the expression of genes encoding five of these candidates (<em>garre1, msh6, zmym3, pias4, smarce1</em>) during <em>X. laevis</em> embryogenesis by in situ hybridization, revealed extensive co-expression of each of these with <em>eya1</em> during placodal development. This suggests potential roles of these candidates in the regulation of placodal neurogenesis possibly in conjunction with Eya1. In gain and loss of function studies of the E3 SUMO-ligase Pias4 and the chromatin modifier Smarce1, we confirm essential roles of both of these proteins for placodal neurogenesis but their mode of interaction with Eya1 remains to be further clarified.</div></div>","PeriodicalId":11070,"journal":{"name":"Developmental biology","volume":"528 ","pages":"Pages 128-142"},"PeriodicalIF":2.1,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145032922","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Rbm8a deficiency causes hematopoietic defects by modulating Wnt/PCP signaling","authors":"Agnese Kocere ,&nbsp;Elena Chiavacci ,&nbsp;Charlotte Soneson ,&nbsp;Seth T. Jacobson ,&nbsp;Emma N. Harrison ,&nbsp;Kevin Manuel Méndez-Acevedo ,&nbsp;Jacalyn S. MacGowan ,&nbsp;Harrison H. Wells ,&nbsp;Max S. Hiltabidle ,&nbsp;Azhwar Raghunath ,&nbsp;Jordan A. Shavit ,&nbsp;Daniela Panáková ,&nbsp;Margot L.K. Williams ,&nbsp;Mark D. Robinson ,&nbsp;Christian Mosimann ,&nbsp;Alexa Burger","doi":"10.1016/j.ydbio.2025.08.021","DOIUrl":"10.1016/j.ydbio.2025.08.021","url":null,"abstract":"<div><div>Thrombocytopenia-Absent Radius (TAR) syndrome is a rare congenital condition with reduced platelets, forelimb anomalies, and variable heart and kidney defects. TAR syndrome is caused by mutations in <em>RBM8A/Y14</em>, a component of the exon junction complex. How perturbing a general mRNA-processing factor causes the selective TAR Syndrome phenotypes remains unknown. Here, we connect zebrafish <em>rbm8a</em> perturbation to early hematopoietic defects via attenuated non-canonical Wnt/Planar Cell Polarity (PCP) signaling. In hypomorphic <em>rbm8a</em> zebrafish, we observe a reduction of <em>cd41</em>-positive thrombocytes. <em>rbm8a</em>-mutant zebrafish accumulate mRNAs with retained introns, including non-canonical Wnt/PCP pathway components resulting in convergent extension defects. We found that reduced <em>rbm8a</em> function interacts with perturbations in non-canonical Wnt/PCP pathway genes w<em>nt5b</em>, <em>wnt11f2</em>, <em>fzd7a</em>, and <em>vangl2</em>, impairing the architecture of the lateral plate mesoderm (LPM) that forms hematopoietic, cardiovascular, kidney, and forelimb skeleton progenitors. Both mutants for <em>rbm8a</em> and for the PCP gene <em>vangl2</em> feature impaired expression of early hematopoietic/endothelial genes <em>runx1</em> and <em>gfi1aa</em>. Together, our data propose aberrant LPM patterning and hematopoietic defects as consequence of attenuated non-canonical Wnt/PCP signaling upon reduced <em>rbm8a</em> function.</div></div>","PeriodicalId":11070,"journal":{"name":"Developmental biology","volume":"528 ","pages":"Pages 34-56"},"PeriodicalIF":2.1,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144999905","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genetic knockout suggests Isl1 enhancer redundancy in mouse hindlimb development","authors":"Seth Olson ,&nbsp;Hiroko Kawakami ,&nbsp;Alexandra Maria Nichitean ,&nbsp;Corinne Boerner ,&nbsp;Amel Awad ,&nbsp;Dylan Corcoran ,&nbsp;Cailin McMahon ,&nbsp;Ryuichi Nishinakamura ,&nbsp;Maureen Cetera ,&nbsp;Yasuhiko Kawakami","doi":"10.1016/j.ydbio.2025.09.014","DOIUrl":"10.1016/j.ydbio.2025.09.014","url":null,"abstract":"<div><div><em>Isl1</em> encodes a LIM homeodomain transcription factor, which is expressed in hindlimb progenitor cells in the lateral plate mesoderm and is required for initiating hindlimb development. Previous studies by lacZ transgenesis in mouse embryos identified a cis-element located 3’ to the <em>Isl1</em> gene, which could drive lacZ reporter expression in hindlimb progenitor cells and the branchial arch ectoderm. We refer to this cis-element as the <em>Isl1</em> hindlimb progenitor enhancer (HLPE). Our previous study also showed that SALL4, a transcription factor, is enriched at the <em>Isl1</em> HLPE, suggesting that SALL4 may regulate <em>Isl1</em> expression through <em>Isl1</em> HLPE. We sought to determine whether <em>Isl1</em> HLPE regulates <em>Isl1</em> expression and created mutant mice that lack the <em>Isl1</em> HLPE sequence by CRISPR/Cas9. The <em>Isl1</em> HLPE^−/− mouse lines, established after breeding with wild-type mice, did not exhibit gross morphological defects, except that their long bones are shorter than those of wild type. The shorter long bone phenotype was observed in the mid-gestation stage and was associated with misregulation of the expression of several chondrogenic genes, suggesting that the deletion of HLPE affects chondrogenesis. Although <em>Sall4</em> regulation of <em>Isl1</em> through <em>Isl1</em> HLPE was suspected, skeletal analysis did not exhibit any synergy between <em>Isl1</em> HLPE^−/− and conditional <em>Sall4</em> mutation. In situ hybridization showed seemingly normal expression of <em>Isl1</em> and its downstream gene <em>Tbx4</em> in <em>Isl1</em> HLPE^−/−, <em>TCre; Sall4</em>^fl/fl mutants, and <em>Isl1</em> HLPE^−/−; <em>TCre; Sall4</em>^fl/fl mutants. Finally, by quantitative gene expression analysis, <em>Isl1</em> expression is reduced but not abolished in <em>Isl1</em> HLPE^−/− and <em>Isl1</em>^+/−; <em>Isl1</em> HLPE ^± embryos, compared to wild-type embryos. Similarly, quantitative imaging analysis after immunostaining showed reduced ISL1 signals in the branchial arch ectoderm in <em>Isl1</em> HLPE^−/− embryos. These results support our notion that the <em>Isl1</em> HLPE sequence functions as an enhancer for <em>Isl1</em> expression in hindlimb progenitor cells and branchial arch ectoderm cells and suggest that multiple redundant enhancers co-regulate <em>Isl1</em> expression.</div></div>","PeriodicalId":11070,"journal":{"name":"Developmental biology","volume":"528 ","pages":"Pages 217-227"},"PeriodicalIF":2.1,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145091246","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Controllable targeted protein degradation as a promising tool for discovery of novel cellular and developmental mechanisms","authors":"De-Li Shi ,&nbsp;Xuan Zhao ,&nbsp;Chengtian Zhao ,&nbsp;Ming Shao","doi":"10.1016/j.ydbio.2025.09.006","DOIUrl":"10.1016/j.ydbio.2025.09.006","url":null,"abstract":"<div><div>Studying the spatial and temporal roles of essential proteins remains technically challenging. The effectiveness of perturbing gene functions using well established approaches upstream of the protein level, such as conditional knockout and RNA interference or morpholino-mediated knockdown, are often dependent upon the turnover rate of pre-existing proteins. Acute targeted protein degradation technologies can circumvent this limitation, and has emerged as powerful tools for discoveries of previously unrecognized protein functions in highly dynamic cellular and developmental processes. Auxin-inducible degron, degrade green fluorescent protein, degradation tag and proteolysis-targeting chimera are efficient for rapid knockdown of degron-tagged or untagged endogenous proteins in a controllable manner. All these approaches harness the evolutionarily conserved multi-protein E3 ubiquitin ligase complex in targeting proteins for degradation by the proteasome, offering versatile applications for protein functional studies in yeasts, plants, invertebrates, and vertebrates. This review presents the understanding of spatial and temporal protein functions advanced by commonly used auxin-inducible degron, degrade green fluorescent protein and degradation tag technologies. It also mentions the promising therapeutic potentials offered by the proteolysis-targeting chimera. With constant improvements, targeted protein degradation will open up new avenues for unprecedented findings of the dynamic features in a living system.</div></div>","PeriodicalId":11070,"journal":{"name":"Developmental biology","volume":"528 ","pages":"Pages 163-173"},"PeriodicalIF":2.1,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145052162","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}