Development Growth & Differentiation最新文献

{"title":"Xenopus: An in vivo model for studying skin response to ultraviolet B irradiation","authors":"Joudi El Mir,&nbsp;Sandrine Fedou,&nbsp;Nadine Thézé,&nbsp;Fanny Morice-Picard,&nbsp;Muriel Cario,&nbsp;Hussein Fayyad-Kazan,&nbsp;Pierre Thiébaud,&nbsp;Hamid-Reza Rezvani","doi":"10.1111/dgd.12848","DOIUrl":"10.1111/dgd.12848","url":null,"abstract":"<p>Ultraviolet B (UVB) in sunlight cause skin damage, ranging from wrinkles to photoaging and skin cancer. UVB can affect genomic DNA by creating cyclobutane pyrimidine dimers (CPDs) and pyrimidine–pyrimidine (6–4) photoproducts (6–4PPs). These lesions are mainly repaired by the nucleotide excision repair (NER) system and by photolyase enzymes that are activated by blue light. Our main goal was to validate the use of <i>Xenopus laevis</i> as an in vivo model system for investigating the impact of UVB on skin physiology. The mRNA expression levels of <i>xpc</i> and six other genes of the NER system and CPD/6–4PP photolyases were found at all stages of embryonic development and in all adult tissues tested. When examining <i>Xenopus</i> embryos at different time points after UVB irradiation, we observed a gradual decrease in CPD levels and an increased number of apoptotic cells, together with an epidermal thickening and an increased dendricity of melanocytes. We observed a quick removal of CPDs when embryos are exposed to blue light versus in the dark, confirming the efficient activation of photolyases. A decrease in the number of apoptotic cells and an accelerated return to normal proliferation rate was noted in blue light-exposed embryos compared with their control counterparts. Overall, a gradual decrease in CPD levels, detection of apoptotic cells, thickening of epidermis, and increased dendricity of melanocytes, emulate human skin responses to UVB and support <i>Xenopus</i> as an appropriate and alternative model for such studies.</p>","PeriodicalId":50589,"journal":{"name":"Development Growth & Differentiation","volume":"65 4","pages":"194-202"},"PeriodicalIF":2.5,"publicationDate":"2023-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/dgd.12848","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9528196","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ccl19 and ccl21 affect cell movements and differentiation in early Xenopus development","authors":"Toshiyasu Goto,&nbsp;Tatsuo Michiue,&nbsp;Hiroshi Shibuya","doi":"10.1111/dgd.12847","DOIUrl":"10.1111/dgd.12847","url":null,"abstract":"<p>We characterized <i>Xenopus laevis C-C motif chemokine ligand 19.L</i> (<i>ccl19.L</i>) and <i>C-C motif chemokine ligand 21.L</i> (<i>ccl21.L</i>) during early <i>Xenopus</i> embryogenesis. The temporal and spatial expression patterns of <i>ccl19.L</i> and <i>ccl21.L</i> tended to show an inverse correlation, except that the expression level was higher in the dorsal side at the gastrula stage. For example, even at the dorsal sector of the gastrulae, <i>ccl19.L</i> was expressed in the axial region and <i>ccl21.L</i> was expressed in the paraxial region. Dorsal overexpression of <i>ccl19.L</i> and <i>ccl21.L</i> and knockdown of Ccl19.L and Ccl21.L inhibited gastrulation, but their functions were different in cell behaviors during morphogenesis. Observation of Keller sandwich explants revealed that overexpression of both <i>ccl19.L</i> and <i>ccl21.L</i> and knockdown of Ccl21.L inhibited the convergent extension movements, while knockdown of Ccl19.L did not. <i>ccl19.L</i>-overexpressing explants attracted cells at a distance and <i>ccl21.L</i>-overexpressing explants attracted neighboring cells. Ventral overexpression of <i>ccl19.L</i> and <i>ccl21.L</i> induced secondary axis-like structures and <i>chrd.1</i> expression at the ventral side. Upregulation of <i>chrd.1</i> was induced by ligand mRNAs through <i>ccr7.S</i>. Knockdown of Ccl19.L and Ccl21.L inhibited gastrulation and downregulated <i>chrd.1</i> expression at the dorsal side. The collective findings indicate that <i>ccl19.L</i> and <i>ccl21.L</i> might play important roles in morphogenesis and dorsal–ventral patterning during early embryogenesis in <i>Xenopus</i>.</p>","PeriodicalId":50589,"journal":{"name":"Development Growth & Differentiation","volume":"65 3","pages":"175-189"},"PeriodicalIF":2.5,"publicationDate":"2023-03-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9244296","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification and characterization of sperm motility-initiating substance-2 gene in internally fertilizing Cynops species","authors":"Haruka Furukawa,&nbsp;Shinya Mito,&nbsp;Jun Nishio,&nbsp;Nozomi Sato,&nbsp;Yoshihiro Ando,&nbsp;Atsushi Tominaga,&nbsp;Fubito Toyama,&nbsp;Yuni Nakauchi,&nbsp;Eriko Takayama-Watanabe,&nbsp;Akihiko Watanabe","doi":"10.1111/dgd.12846","DOIUrl":"10.1111/dgd.12846","url":null,"abstract":"<p>Sperm motility-initiating substance (SMIS) is an oviductal protein critical for internal fertilization in urodeles. It contributes to the establishment of various reproductive modes in amphibians and is thus a unique research model for the gene evolution of gamete-recognizing ligands that have diversified among animal species. In this study, a paralogous SMIS gene, <i>smis2</i>, was identified via the RNA sequencing of the oviduct of the newt, <i>Cynops pyrrhogaster</i>. The base sequence of the <i>smis2</i> gene was homologous (˃90%) to that of the original <i>smis</i> gene (<i>smis1</i>), and deduced amino acid sequences of both genes conserved six cysteine residues essential for the cysteine knot motif. Furthermore, <i>smis2</i> complementary DNA was identified in the oviduct of <i>Cynops ensicauda</i>, and the base substitution patterns also suggested that the <i>smis</i> gene was duplicated in the Salamandridae. Nonsynonymous/synonymous substitution ratios of <i>smis1</i> and <i>smis2</i> genes were 0.79 and 2.6, respectively, suggesting that <i>smis2</i> gene evolution was independently driven by positive selection. Amino acid substitutions were concentrated in the cysteine knot motif of SMIS2. The <i>smis2</i> gene was expressed in some organs in addition to the oviduct; in contrast, SMIS1 was only expressed in the oviduct. The SMIS2 protein was suggested to be produced and secreted at least in the oviduct and redundantly act in sperm. These results suggest that <i>smis1</i> plays the original role in the oviduct, whereas <i>smis2</i> may undergo neofunctionalization, which rarely occurs in gene evolution.</p>","PeriodicalId":50589,"journal":{"name":"Development Growth & Differentiation","volume":"65 3","pages":"144-152"},"PeriodicalIF":2.5,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9607513","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The origin of life: RNA and protein co-evolution on the ancient Earth","authors":"Shunsuke Tagami,&nbsp;Peiying Li","doi":"10.1111/dgd.12845","DOIUrl":"10.1111/dgd.12845","url":null,"abstract":"<p>How life emerged from simple non-life chemicals on the ancient Earth is one of the greatest mysteries in biology. The gene expression system of extant life is based on the interdependence between multiple molecular species (DNA, RNA, and proteins). While DNA is mainly used as genetic material and proteins as functional molecules in modern biology, RNA serves as both genetic material and enzymes (ribozymes). Thus, the evolution of life may have begun with the birth of a ribozyme that replicated itself (the RNA world hypothesis), and proteins and DNA joined later. However, the complete self-replication of ribozymes from monomeric substrates has not yet been demonstrated experimentally, due to their limited activity and stability. In contrast, peptides are more chemically stable and are considered to have existed on the ancient Earth, leading to the hypothesis of RNA–peptide co-evolution from the very beginning. Our group and collaborators recently demonstrated that (1) peptides with both hydrophobic and cationic moieties (e.g., KKVVVVVV) form β-amyloid aggregates that adsorb RNA and enhance RNA synthesis by an artificial RNA polymerase ribozyme and (2) a simple peptide with only seven amino acid types (especially rich in valine and lysine) can fold into the ancient β-barrel conserved in various enzymes, including the core of cellular RNA polymerases. These findings, together with recent reports from other groups, suggest that simple prebiotic peptides could have supported the ancient RNA-based replication system, gradually folded into RNA-binding proteins, and eventually evolved into complex proteins like RNA polymerase.</p>","PeriodicalId":50589,"journal":{"name":"Development Growth & Differentiation","volume":"65 3","pages":"167-174"},"PeriodicalIF":2.5,"publicationDate":"2023-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9243793","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Osteological and histological comparison of the development of the interphalangeal intercalary skeletal element between hyloid and ranoid anurans","authors":"Kensuke Nakanishi,&nbsp;Nao Hasegawa,&nbsp;Koichi Takeo,&nbsp;Keisuke Nakajima,&nbsp;Nobuaki Furuno,&nbsp;Ichiro Tazawa","doi":"10.1111/dgd.12844","DOIUrl":"10.1111/dgd.12844","url":null,"abstract":"<p>Some frog species have a unique skeletal element, referred to as the intercalary element (IE), in the joints between the terminal and subterminal phalanges of all digits. IEs are composed of cartilage or connective tissue and have a markedly differ shape than the phalanges. IEs are highly related to the arboreal lifestyle and toe pads. The IE is found only in neobatrachian frogs among anurans, suggesting that it is a novelty of Neobatrachia. IEs are widely distributed among multiple neobatrachian lineages and are found in the suborders Hyloides and Ranoides (the two major clades in Neobatrachia). However, it is unclear whether the IEs found in multiple linages resulted from convergent evolution. Therefore, in this study, we aimed to examine how similar or different the developmental trajectories of the IEs are between Hyloides and Ranoides. To that end, we compared the osteological and histological developmental processes of the IEs of the hyloid frog <i>Dryophytes japonicus</i> and the ranoid frog <i>Zhangixalus schlegelii</i>. Both species shared the same IE-initiation site and level of tissue differentiation around the IE when it began to form in tadpoles, although the IE developments initiated at different stages which were determined by external criteria. These results suggest that similar mechanisms drive IE formation in the digits of both species, supporting the hypothesis that the IEs did not evolve convergently.</p>","PeriodicalId":50589,"journal":{"name":"Development Growth & Differentiation","volume":"65 2","pages":"100-108"},"PeriodicalIF":2.5,"publicationDate":"2023-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10790792","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Versatile utilities of amphibians (part 4)","authors":"Haruki Ochi,&nbsp;Tatsuo Michiue,&nbsp;Takashi Kato,&nbsp;Aaron Zorn,&nbsp;Toshinori Hayashi,&nbsp;Takeshi Inoue,&nbsp;Mariko Kondo,&nbsp;Masanori Taira","doi":"10.1111/dgd.12838","DOIUrl":"10.1111/dgd.12838","url":null,"abstract":"We have published the special issue “Versatile utilities of amphibians” in Part 1 (8 articles, Issue 6, 2022), Part 2 (3 articles, Issue 7, 2022), and Part 3 (5 articles, Issue 8, 2022) (see Michiue, Zorn, et al., 2022a, 2022b; Michiue, Kato, et al., 2022 for the previous Prefaces). Here, Part 4 is released with one research article and three short research articles. Konno (2023) focused on the metabolic transformation from ammonotelism to ureotelism during development in Xenopus laevis and found that simultaneous increase of urea cycle and gluconeogenetic enzymes' gene expression coincides with a corticoid surge occurring prior to metamorphosis. This finding may lead to understanding of the metabolic changes preceding metamorphosis, which may be closely related to the onset of the feeding and nutrient accumulation required for metamorphosis. Kondo et al. (2023) applied micro-CT (computed tomography) to analyze frog cortical bones and found that three Ceratophryidae species have porous cortical bones that is observed in reptiles, avians, and mammals. These data suggest that the process of fibrolamellar bone formation arose evolutionarily in amphibians. Further studies of the molecular mechanism of porous or non-porous bone formation in frogs may provide an evolutionary understanding of tetrapod bone structures. The molecular mechanism of amphibian metamorphosis is a longstanding question. Tanizaki et al. (2023) made a thyroid hormone receptor α (TRα) knockout (KO) frog using Xenopus tropicalis with the CRISPR/Cas9 genome editing technology. They performed chromatin immunoprecipitation-sequencing (ChIP-seq) to identify genes bound by TR in the tail of premetamorphic wild type or TRα KO tadpoles with or without T3 treatment, in comparison with the intestine and hindlimb. These ChIPseq datasets clearly showed tissue-specific roles in regulating T3-dependent metamorphosis by directly targeting the genes for metamorphosis, in which TRα is less important in tail regression duringmetamorphosis. Axis formation is a crucial step in establishing the body plan and amphibians have long been used as a model organism to study this. β-catenin protein stability is essential for axis formation and is regulated via canonical Wnt signaling. Goto and Shibuya (2023) analyzed the function and developmental role of the E3 ubiquitin ligase Maea (Macrophage erythroblast attacher) during early Xenopus laevis development. They found that Maea ubiquitinates β-catenin which leads to beta-catenin degradation through ubiquitination of yet identified sites, because β-catenin mutated in all four known ubiquitination Lys sites was still ubiquitinated and degraded by Maea. In addition, using lossand gain-of-function analyses, the data suggest that maea.L and maea.S homeologous genes contribute to head formation. Thus, they identified an additional new player for Xenopus head formation through ß-catenin degradation. Above are examples of the versatility of amphibian researches, com","PeriodicalId":50589,"journal":{"name":"Development Growth & Differentiation","volume":"65 1","pages":"4-5"},"PeriodicalIF":2.5,"publicationDate":"2023-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9154634","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ndst1, a heparan sulfate modification enzyme, regulates neuroectodermal patterning by enhancing Wnt signaling in Xenopus","authors":"Takayoshi Yamamoto,&nbsp;Yuta Kambayashi,&nbsp;Kohei Tsukano,&nbsp;Tatsuo Michiue","doi":"10.1111/dgd.12843","DOIUrl":"10.1111/dgd.12843","url":null,"abstract":"<p>Neural tissue is derived from three precursor regions: neural plate, neural crest, and preplacodal ectoderm. These regions are determined by morphogen-mediated signaling. Morphogen distribution is generally regulated by binding to an extracellular matrix component, heparan sulfate (HS) proteoglycan. HS is modified by many enzymes, such as N-deacetyl sulfotransferase 1 (Ndst1), which is highly expressed in early development. However, functions of HS modifications in ectodermal patterning are largely unknown. In this study, we analyzed the role of Ndst1 using <i>Xenopus</i> embryos. We found that <i>ndst1</i> was expressed in anterior neural plate and the trigeminal region at the neurula stage. <i>ndst1</i> overexpression expanded the neural crest (NC) region, whereas translational inhibition reduced not only the trigeminal region, but also the adjacent NC region, especially the anterior part. At a later stage, <i>ndst1</i> knocked-down embryos showed defects in cranial ganglion formation. We also found that Ndst1 activates Wnt signaling pathway at the neurula stage. Taken together, our results suggest that N-sulfonated HS accumulates Wnt ligand and activates Wnt signaling in <i>ndst1</i>-expressing cells, but that it inhibits signaling in non-<i>ndst1</i>-expressing cells, leading to proper neuroectodermal patterning.</p>","PeriodicalId":50589,"journal":{"name":"Development Growth & Differentiation","volume":"65 3","pages":"153-160"},"PeriodicalIF":2.5,"publicationDate":"2023-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/dgd.12843","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9264775","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Theoretical approaches for understanding the self-organized formation of the Golgi apparatus","authors":"Masashi Tachikawa","doi":"10.1111/dgd.12842","DOIUrl":"10.1111/dgd.12842","url":null,"abstract":"<p>Eukaryotic cells fold their membranes into highly organized structures called membrane-bound organelles. Organelles display characteristic structures and perform specialized functions related to their structures. Focusing on the Golgi apparatus, we provide an overview of recent theoretical studies to explain the mechanism of the architecture of the Golgi apparatus. These studies are classified into two categories: those that use equilibrium models to describe the robust Golgi morphology and those that use non-equilibrium models to explain the stationarity of the Golgi structures and the constant streaming of membrane traffic. A combinational model of both categories was used for computational reconstruction of the de novo Golgi formation process, which might provide an insight into the integrated understanding of the Golgi structure.</p>","PeriodicalId":50589,"journal":{"name":"Development Growth & Differentiation","volume":"65 3","pages":"161-166"},"PeriodicalIF":2.5,"publicationDate":"2023-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/dgd.12842","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9606965","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Appendage-restricted gene induction using a heated agarose gel for studying regeneration in metamorphosed Xenopus laevis and Pleurodeles waltl","authors":"Haruka Matsubara,&nbsp;Aiko Kawasumi-Kita,&nbsp;Saki Nara,&nbsp;Hibiki Yokoyama,&nbsp;Toshinori Hayashi,&nbsp;Takashi Takeuchi,&nbsp;Hitoshi Yokoyama","doi":"10.1111/dgd.12841","DOIUrl":"10.1111/dgd.12841","url":null,"abstract":"<p>Amphibians and fish often regenerate lost parts of their appendages (tail, limb, and fin) after amputation. Limb regeneration in adult amphibians provides an excellent model for appendage (limb) regeneration through 3D morphogenesis along the proximodistal, dorsoventral, and anteroposterior axes in mammals, because the limb is a homologous organ among amphibians and mammals. However, manipulating gene expression in specific appendages of adult amphibians remains difficult; this in turn hinders elucidation of the molecular mechanisms underlying appendage regeneration. To address this problem, we devised a system for appendage-specific gene induction using a simplified protocol named the “agarose-embedded heat shock (AeHS) method” involving the combination of a heat-shock-inducible system and insertion of an appendage in a temperature-controlled agarose gel. Gene expression was then induced specifically and ubiquitously in the regenerating limbs of metamorphosed amphibians, including a frog (<i>Xenopus laevis</i>) and newt (<i>Pleurodeles waltl</i>). We also induced gene expression in the regenerating tail of a metamorphosed <i>P. waltl</i> newt using the same method. This method can be applied to adult amphibians with large body sizes. Furthermore, this method enables simultaneous induction of gene expression in multiple individuals; further, the data are obtained in a reproducible manner, enabling the analysis of gene functions in limb and tail regeneration. Therefore, this method will facilitate elucidation of the molecular mechanisms underlying appendage regeneration in amphibians, which can support the development of regenerative therapies for organs, such as the limbs and spinal cord.</p>","PeriodicalId":50589,"journal":{"name":"Development Growth & Differentiation","volume":"65 2","pages":"86-93"},"PeriodicalIF":2.5,"publicationDate":"2023-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10780870","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The role of p63 in embryonic external genitalia outgrowth in mice","authors":"Kosei Tanaka,&nbsp;Daisuke Matsumaru,&nbsp;Kentaro Suzuki,&nbsp;Gen Yamada,&nbsp;Shinichi Miyagawa","doi":"10.1111/dgd.12840","DOIUrl":"10.1111/dgd.12840","url":null,"abstract":"<p>Embryonic external genitalia (genital tubercle [GT]) protrude from the cloaca and outgrow as cloacal development progresses. Individual gene functions and knockout phenotypes in GT development have been extensively analyzed; however, the interactions between these genes are not fully understood. In this study, we investigated the role of p63, focusing on its interaction with the Shh–Wnt/Ctnnb1–Fgf8 pathway, a signaling network that is known to play a role in GT outgrowth. p63 was expressed in the epithelial tissues of the GT at E11.5, and the distal tip of the GT predominantly expressed the ΔNp63α isoform. The GTs in <i>p63</i> knockout embryos had normal <i>Shh</i> expression, but CTNNB1 protein and <i>Fgf8</i> gene expression in the distal urethral epithelium was decreased or lost. Constitutive expression of CTNNB1 in <i>p63</i>-null embryos restored <i>Fgf8</i> expression, accompanied by small bud structure development; however, such bud structures could not be maintained by E13.5, at which point mutant GTs exhibited severe abnormalities showing a split shape with a hemorrhagic cloaca. Therefore, p63 is a key component of the signaling pathway that triggers <i>Fgf8</i> expression in the distal urethral epithelium and contributes to GT outgrowth by ensuring the structural integrity of the cloacal epithelia. Altogether, we propose that p63 plays an essential role in the signaling network for the development of external genitalia.</p>","PeriodicalId":50589,"journal":{"name":"Development Growth & Differentiation","volume":"65 2","pages":"132-140"},"PeriodicalIF":2.5,"publicationDate":"2023-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/dgd.12840","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10795649","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}