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1.
Nature ; 613(7942): 153-159, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36517597

RESUMO

Sequential segmentation creates modular body plans of diverse metazoan embryos1-4. Somitogenesis establishes the segmental pattern of the vertebrate body axis. A molecular segmentation clock in the presomitic mesoderm sets the pace of somite formation4. However, how cells are primed to form a segment boundary at a specific location remains unclear. Here we developed precise reporters for the clock and double-phosphorylated Erk (ppErk) gradient in zebrafish. We show that the Her1-Her7 oscillator drives segmental commitment by periodically lowering ppErk, therefore projecting its oscillation onto the ppErk gradient. Pulsatile inhibition of the ppErk gradient can fully substitute for the role of the clock, and kinematic clock waves are dispensable for sequential segmentation. The clock functions upstream of ppErk, which in turn enables neighbouring cells to discretely establish somite boundaries in zebrafish5. Molecularly divergent clocks and morphogen gradients were identified in sequentially segmenting species3,4,6-8. Our findings imply that versatile clocks may establish sequential segmentation in diverse species provided that they inhibit gradients.


Assuntos
Padronização Corporal , MAP Quinases Reguladas por Sinal Extracelular , Periodicidade , Somitos , Proteínas de Peixe-Zebra , Peixe-Zebra , Animais , Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Regulação da Expressão Gênica no Desenvolvimento , Somitos/efeitos dos fármacos , Somitos/embriologia , Somitos/enzimologia , Somitos/metabolismo , Peixe-Zebra/embriologia , Peixe-Zebra/metabolismo , Proteínas de Peixe-Zebra/antagonistas & inibidores , Proteínas de Peixe-Zebra/metabolismo , Relógios Biológicos , MAP Quinases Reguladas por Sinal Extracelular/antagonistas & inibidores , MAP Quinases Reguladas por Sinal Extracelular/metabolismo
2.
Nat Commun ; 13(1): 7934, 2022 12 24.
Artigo em Inglês | MEDLINE | ID: mdl-36566327

RESUMO

Classic microsurgical techniques, such as those used in the early 1900s by Mangold and Spemann, have been instrumental in advancing our understanding of embryonic development. However, these techniques are highly specialized, leading to issues of inter-operator variability. Here we introduce a user-friendly robotic microsurgery platform that allows precise mechanical manipulation of soft tissues in zebrafish embryos. Using our platform, we reproducibly targeted precise regions of tail explants, and quantified the response in real-time by following notochord and presomitic mesoderm (PSM) morphogenesis and segmentation clock dynamics during vertebrate anteroposterior axis elongation. We find an extension force generated through the posterior notochord that is strong enough to buckle the structure. Our data suggest that this force generates a unidirectional notochord extension towards the tailbud because PSM tissue around the posterior notochord does not let it slide anteriorly. These results complement existing biomechanical models of axis elongation, revealing a critical coupling between the posterior notochord, the tailbud, and the PSM, and show that somite patterning is robust against structural perturbations.


Assuntos
Robótica , Peixe-Zebra , Animais , Morfogênese , Somitos , Mesoderma , Notocorda/fisiologia , Micromanipulação , Padronização Corporal/fisiologia
3.
EMBO J ; 41(23): e110928, 2022 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-36245268

RESUMO

Each vertebrate species appears to have a unique timing mechanism for forming somites along the vertebral column, and the process in human remains poorly understood at the molecular level due to technical and ethical limitations. Here, we report the reconstitution of human segmentation clock by direct reprogramming. We first reprogrammed human urine epithelial cells to a presomitic mesoderm (PSM) state capable of long-term self-renewal and formation of somitoids with an anterior-to-posterior axis. By inserting the RNA reporter Pepper into HES7 and MESP2 loci of these iPSM cells, we show that both transcripts oscillate in the resulting somitoids at ~5 h/cycle. GFP-tagged endogenous HES7 protein moves along the anterior-to-posterior axis during somitoid formation. The geo-sequencing analysis further confirmed anterior-to-posterior polarity and revealed the localized expression of WNT, BMP, FGF, and RA signaling molecules and HOXA-D family members. Our study demonstrates the direct reconstitution of human segmentation clock from somatic cells, which may allow future dissection of the mechanism and components of such a clock and aid regenerative medicine.


Assuntos
Mesoderma , Somitos , Humanos , Somitos/metabolismo , Mesoderma/metabolismo , Transdução de Sinais , Regulação da Expressão Gênica no Desenvolvimento , Padronização Corporal/genética , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo
4.
Elife ; 112022 10 12.
Artigo em Inglês | MEDLINE | ID: mdl-36223168

RESUMO

Living systems exhibit an unmatched complexity, due to countless, entangled interactions across scales. Here, we aim to understand a complex system, that is, segmentation timing in mouse embryos, without a reference to these detailed interactions. To this end, we develop a coarse-grained approach, in which theory guides the experimental identification of the segmentation clock entrainment responses. We demonstrate period- and phase-locking of the segmentation clock across a wide range of entrainment parameters, including higher-order coupling. These quantifications allow to derive the phase response curve (PRC) and Arnold tongues of the segmentation clock, revealing its essential dynamical properties. Our results indicate that the somite segmentation clock has characteristics reminiscent of a highly non-linear oscillator close to an infinite period bifurcation and suggests the presence of long-term feedbacks. Combined, this coarse-grained theoretical-experimental approach reveals how we can derive simple, essential features of a highly complex dynamical system, providing precise experimental control over the pace and rhythm of the somite segmentation clock.


Assuntos
Somitos , Língua , Animais , Camundongos
5.
Biol Open ; 11(8)2022 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-35972050

RESUMO

To address questions of stem cell diversity during skeletal myogenesis, a Brainbow-like genetic cell lineage tracing method, dubbed Musclebow2, was derived by enhancer trapping in zebrafish. It is shown that, after initial formation of the primary myotome, at least 15 muscle precursor cells (mpcs) seed each somite, where they proliferate but contribute little to muscle growth prior to hatching. Thereafter, dermomyotome-derived mpc clones rapidly expand while some progeny undergo terminal differentiation, leading to stochastic clonal drift within the mpc pool. No evidence of cell-lineage-based clonal fate diversity was obtained. Neither fibre nor mpc death was observed in uninjured animals. Individual marked muscle fibres persist across much of the lifespan indicating low rates of nuclear turnover. In adulthood, early-marked mpc clones label stable blocks of tissue comprising a significant fraction of either epaxial or hypaxial somite. Fusion of cells from separate early-marked clones occurs in regions of clone overlap. Wounds are regenerated from several local mpcs; no evidence for specialised stem mpcs was obtained. In conclusion, our data indicate that most mpcs in muscle tissue contribute to local growth and repair and suggest that cellular turnover is low in the absence of trauma.


Assuntos
Longevidade , Peixe-Zebra , Animais , Desenvolvimento Muscular , Músculo Esquelético , Somitos/metabolismo
6.
Nature ; 610(7930): 143-153, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-36007540

RESUMO

Embryonic stem (ES) cells can undergo many aspects of mammalian embryogenesis in vitro1-5, but their developmental potential is substantially extended by interactions with extraembryonic stem cells, including trophoblast stem (TS) cells, extraembryonic endoderm stem (XEN) cells and inducible XEN (iXEN) cells6-11. Here we assembled stem cell-derived embryos in vitro from mouse ES cells, TS cells and iXEN cells and showed that they recapitulate the development of whole natural mouse embryo in utero up to day 8.5 post-fertilization. Our embryo model displays headfolds with defined forebrain and midbrain regions and develops a beating heart-like structure, a trunk comprising a neural tube and somites, a tail bud containing neuromesodermal progenitors, a gut tube, and primordial germ cells. This complete embryo model develops within an extraembryonic yolk sac that initiates blood island development. Notably, we demonstrate that the neurulating embryo model assembled from Pax6-knockout ES cells aggregated with wild-type TS cells and iXEN cells recapitulates the ventral domain expansion of the neural tube that occurs in natural, ubiquitous Pax6-knockout embryos. Thus, these complete embryoids are a powerful in vitro model for dissecting the roles of diverse cell lineages and genes in development. Our results demonstrate the self-organization ability of ES cells and two types of extraembryonic stem cells to reconstitute mammalian development through and beyond gastrulation to neurulation and early organogenesis.


Assuntos
Embrião de Mamíferos , Gastrulação , Modelos Biológicos , Neurulação , Organogênese , Animais , Linhagem da Célula , Embrião de Mamíferos/citologia , Embrião de Mamíferos/embriologia , Células-Tronco Embrionárias/citologia , Endoderma/citologia , Endoderma/embriologia , Coração/embriologia , Mesencéfalo/embriologia , Camundongos , Tubo Neural/embriologia , Fator de Transcrição PAX6/deficiência , Fator de Transcrição PAX6/genética , Prosencéfalo/embriologia , Somitos/embriologia
7.
Int J Mol Sci ; 23(15)2022 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-35955736

RESUMO

The river lamprey (L. fluviatilis) is a representative of the ancestral jawless vertebrate group. We performed a histological analysis of trunk muscle fiber differentiation during embryonal, larval, and adult musculature development in this previously unstudied species. Investigation using light, transmission electron (TEM), and confocal microscopy revealed that embryonal and larval musculature differs from adult muscle mass. Here, we present the morphological analysis of L. fluviatilis myogenesis, from unsegmented mesoderm through somite formation, and their differentiation into multinucleated muscle lamellae. Our analysis also revealed the presence of myogenic factors LfPax3/7 and Myf5 in the dermomyotome. In the next stages of development, two types of muscle lamellae can be distinguished: central surrounded by parietal. This pattern is maintained until adulthood, when parietal muscle fibers surround the central muscles on both sides. The two types show different morphological characteristics. Although lampreys are phylogenetically distant from jawed vertebrates, somite morphology, especially dermomyotome function, shows similarity. Here we demonstrate that somitogenesis is a conservative process among all vertebrates. We conclude that river lamprey myogenesis shares features with both ancestral and higher vertebrates.


Assuntos
Lampreias , Rios , Animais , Lampreias/fisiologia , Larva , Desenvolvimento Muscular , Somitos , Vertebrados
8.
Differentiation ; 127: 1-11, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36041259

RESUMO

The cervical and anterior thoracic regions of mammals generally exhibit similar vertebral numbers and identities along the anterior-posterior axis. The position of the forelimbs along the axial skeleton is also generally conserved. In contrast, the number of lumbar and sacral vertebrae and pelvic position exhibit more variation, correlating with posture and locomotion. The molecular mechanisms that lead to these conserved and variable axial skeletal patterns between species are not fully understood. Here we use a human HOXB1-9 transgene to complement a HoxB1-9 deficiency in the mouse. In TgHOXB1-9 mice, human HOXB1, B2, B3, and B4 (HOXB1-4) genes were expressed in mouse embryos in patterns similar to mouse Hoxb1-4 genes. Human transgene expression rescued the cervical and anterior thoracic vertebral patterning defects of HoxB1-9Δ/Δ mice. In addition, the posterior shift in forelimb position of HoxB1-9Δ/Δ mice was rescued by the transgene. Interestingly, the position of the lumbar-sacral transition in both TgHOXB1-9; HoxB1-9Δ/Δ and TgHOXB1-9; HoxB1-9+/+ mice was altered from six lumbar and four sacral vertebrae found in wild-type controls to five lumbar and five sacral vertebrae. The change in the position of the lumbar-sacral transition consequently altered the position of the pelvis. In contrast to the conserved expression of human HOXB1-4 genes in TgHOXB1-9 mouse embryos, the anterior border of human HOXB9 expression in the neural tube and paraxial mesoderm was shifted posteriorly by 2-3 somites compared to the anterior boundary of endogenous Hoxb9 expression. These findings suggest that conservation and variation in Hoxb/HOXB expression contributes to conserved and species-specific vertebral pattern and limb position.


Assuntos
Genes Homeobox , Somitos , Animais , Osso e Ossos , Regulação da Expressão Gênica no Desenvolvimento/genética , Proteínas de Homeodomínio/genética , Humanos , Mamíferos/genética , Mamíferos/metabolismo , Camundongos , Camundongos Transgênicos , Coluna Vertebral/metabolismo , Fatores de Transcrição/genética
9.
Methods Mol Biol ; 2525: 321-332, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35836080

RESUMO

Somites are formed sequentially by the segmentation of the anterior parts of the presomitic mesoderm (PSM), and such periodical somite formation is crucial to ensure the proper vertebrae. In the mouse embryo, Hes7, a segmentation clock gene, controls this periodic event with new somites forming every 2 h. Hes7 oscillations are synchronized between neighboring PSM cells and propagate from the posterior to the anterior PSM in the form of traveling waves. However, the exact mechanisms that generate these oscillatory dynamics and control synchronization are still unclear. Given that the half-life of Hes7 is too short to be monitored with most fluorescent proteins, time-lapse bioluminescence imaging (BLI) is a suitable tool to monitor the chronological Hes7 expression dynamics. In this chapter, we introduce a ubiquitinated luciferase reporter which enables the visualization of Hes7 expression dynamics with high temporal and spatial resolution in living cells and tissues.


Assuntos
Fatores de Transcrição Hélice-Alça-Hélice Básicos , Somitos , Animais , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Embrião de Mamíferos/metabolismo , Regulação da Expressão Gênica no Desenvolvimento , Mesoderma/metabolismo , Camundongos , Somitos/metabolismo , Imagem com Lapso de Tempo
10.
Cells ; 11(13)2022 06 22.
Artigo em Inglês | MEDLINE | ID: mdl-35805087

RESUMO

Fibronectin is essential for somite formation in the vertebrate embryo. Fibronectin matrix assembly starts as cells emerge from the primitive streak and ingress in the unsegmented presomitic mesoderm (PSM). PSM cells undergo cyclic waves of segmentation clock gene expression, followed by Notch-dependent upregulation of meso1 in the rostral PSM which induces somite cleft formation. However, the relevance of the fibronectin matrix for these molecular processes remains unknown. Here, we assessed the role of the PSM fibronectin matrix in the spatio-temporal regulation of chick embryo somitogenesis by perturbing (1) extracellular fibronectin matrix assembly, (2) integrin-fibronectin binding, (3) Rho-associated protein kinase (ROCK) activity and (4) non-muscle myosin II (NM II) function. We found that integrin-fibronectin engagement and NM II activity are required for cell polarization in the nascent somite. All treatments resulted in defective somitic clefts and significantly perturbed meso1 and segmentation clock gene expression in the PSM. Importantly, inhibition of actomyosin-mediated contractility increased the period of hairy1/hes4 oscillations from 90 to 120 min. Together, our work strongly suggests that the fibronectin-integrin-ROCK-NM II axis regulates segmentation clock dynamics and dictates the spatio-temporal localization of somitic clefts.


Assuntos
Actomiosina , Somitos , Actomiosina/metabolismo , Animais , Relógios Biológicos/fisiologia , Embrião de Galinha , Fibronectinas/metabolismo , Integrinas/metabolismo , Somitos/metabolismo
11.
Dev Biol ; 490: 13-21, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-35779606

RESUMO

The head-tail axis in birds and mammals develops from a growth zone in the tail-end, which contains the node. This growth zone then forms the tailbud. Labelling experiments have shown that while many cells leave the node and tailbud to contribute to axial (notochord, floorplate) and paraxial (somite) structures, some cells remain resident in the node and tailbud. Could these cells be resident axial stem cells? If so, do the node and tailbud represent an instructive stem cell niche that specifies and maintains these stem cells? Serial transplantation and single cell labelling studies support the existence of self-renewing stem cells and heterotopic transplantations suggest that the node can instruct such self-renewing behaviour. However, only single cell manipulations can reveal whether self-renewing behaviour occurs at the level of a cell population (asymmetric or symmetric cell divisions) or at the level of single cells (asymmetric divisions only). We combine data on resident cells in the node and tailbud and review it in the context of axial development in chick and mouse, summarising our current understanding of axial stem cells and their niche and highlighting future directions of interest.


Assuntos
Somitos , Células-Tronco , Animais , Divisão Celular , Mamíferos , Mesoderma , Camundongos , Notocorda
12.
J Vis Exp ; (184)2022 06 17.
Artigo em Inglês | MEDLINE | ID: mdl-35781468

RESUMO

The body axis of vertebrate embryos is periodically subdivided into 3D multicellular units called somites. While genetic oscillations and molecular prepatterns determine the initial length-scale of somites, mechanical processes have been implicated in setting their final size and shape. To better understand the intrinsic material properties of somites, a method is developed to culture single-somite explant from zebrafish embryos. Single somites are isolated by first removing the skin of embryos, followed by yolk removal and sequential excision of neighboring tissues. Using transgenic embryos, the distribution of various sub-cellular structures can be observed by fluorescent time-lapse microscopy. Dynamics of explanted somites can be followed for several hours, thus providing an experimental framework for studying tissue-scale shape changes at single-cell resolution. This approach enables direct mechanical manipulation of somites, allowing for dissection of the material properties of the tissue. Finally, the technique outlined here can be readily extended for explanting other tissues such as the notochord, neural plate, and lateral plate mesoderm.


Assuntos
Somitos , Peixe-Zebra , Animais , Mesoderma , Notocorda , Somitos/cirurgia
13.
Dev Biol ; 488: 120-130, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35644252

RESUMO

We previously showed the importance of TGFß signaling in development of the mouse axial skeleton. Here, we provide the first direct evidence that TGFß signaling is required for resegmentation of the sclerotome using chick embryos. Lipophilic fluorescent tracers, DiO and DiD, were microinjected into adjacent somites of embryos treated with or without TGFßRI inhibitors, SB431542, SB525334 or SD208, at developmental day E2.5 (HH16). Lineage tracing of labeled cells was observed over the course of 4 days until the completion of resegmentation at E6.5 (HH32). Vertebrae were malformed and intervertebral discs were small and misshapen in inhibitor injected embryos. Hypaxial myofibers were also increased in thickness after treatment with the inhibitor. Inhibition of TGFß signaling resulted in alterations in resegmentation that ranged between full, partial, and slanted shifts in distribution of DiO or DiD labeled cells within vertebrae. Patterning of rostro-caudal markers within sclerotome was disrupted at E3.5 after treatment with TGFßRI inhibitor with rostral domains expressing both rostral and caudal markers. We propose that TGFß signaling regulates rostro-caudal polarity and subsequent resegmentation in sclerotome during spinal column development.


Assuntos
Galinhas , Disco Intervertebral , Animais , Osso e Ossos , Embrião de Galinha , Somitos/fisiologia , Coluna Vertebral/fisiologia , Fator de Crescimento Transformador beta
14.
Development ; 149(13)2022 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-35686648

RESUMO

A fundamental requirement for embryonic development is the coordination of signaling activities in space and time. A notable example in vertebrate embryos is found during somitogenesis, where gene expression oscillations linked to the segmentation clock are synchronized across cells in the presomitic mesoderm (PSM) and result in tissue-level wave patterns. To examine their onset during mouse embryo development, we studied the dynamics of the segmentation clock gene Lfng during gastrulation. To this end, we established an imaging setup using selective plane illumination microscopy (SPIM) that enables culture and simultaneous imaging of up to four embryos ('SPIM- for-4'). Using SPIM-for-4, combined with genetically encoded signaling reporters, we detected the onset of Lfng oscillations within newly formed mesoderm at presomite stages. Functionally, we found that initial synchrony and the first ∼6-8 oscillation cycles occurred even when Notch signaling was impaired, revealing similarities to previous findings made in zebrafish embryos. Finally, we show that a spatial period gradient is present at the onset of oscillatory activity, providing a potential mechanism accounting for our observation that wave patterns build up gradually over the first oscillation cycles.


Assuntos
Gastrulação , Somitos , Animais , Regulação da Expressão Gênica no Desenvolvimento , Glicosiltransferases/genética , Glicosiltransferases/metabolismo , Mesoderma/metabolismo , Camundongos , Receptores Notch/genética , Receptores Notch/metabolismo , Somitos/metabolismo , Peixe-Zebra/genética
15.
J Anat ; 241(3): 831-845, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35751554

RESUMO

In the thorax of higher vertebrates, ribs and intercostal muscles play a decisive role in stability and respiratory movements of the body wall. They are derivatives of the somites, the ribs originating in the sclerotome and the intercostal muscles originating in the myotome. During thorax development, ribs and intercostal muscles extend into the lateral plate mesoderm and eventually contact the sternum during ventral closure. Here, we give a detailed description of the morphogenesis of ribs and thoracic muscles in the chicken embryo (Gallus gallus). Using Alcian blue staining as well as Sox9 and Desmin whole-mount immunohistochemistry, we monitor synchronously the development of rib cartilage and intercostal muscle anlagen. We show that the muscle anlagen precede the rib anlagen during ventrolateral extension, which is in line with the inductive role of the myotome in rib differentiation. Our studies furthermore reveal the temporary formation of a previously unknown eighth rib in the chicken embryonic thorax.


Assuntos
Galinhas , Músculos Intercostais , Animais , Embrião de Galinha , Músculos Intercostais/fisiologia , Músculo Esquelético , Costelas , Somitos
16.
Curr Top Dev Biol ; 149: 341-372, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35606060

RESUMO

Tight spatiotemporal control of cellular behavior and cell fate decisions is paramount to the formation of multicellular organisms during embryonic development. Intercellular communication via signaling pathways mediates this control. Interestingly, these signaling pathways are not static, but dynamic and change in activity over time. Signaling oscillations as a specific type of dynamics are found in various signaling pathways and model systems. Functions of oscillations include the regulation of periodic events or the transmission of information by encoding signals in the dynamic properties of a signaling pathway. For instance, signaling oscillations in neural or pancreatic progenitor cells modulate their proliferation and differentiation. Oscillations between neighboring cells can also be synchronized, leading to the emergence of waves traveling through the tissue. Such population-wide signaling oscillations regulate for example the consecutive segmentation of vertebrate embryos, a process called somitogenesis. Here, we outline our current understanding of signaling oscillations in embryonic development, how signaling oscillations are generated, how they are studied and how they contribute to the regulation of embryonic development.


Assuntos
Receptores Notch , Somitos , Comunicação Celular , Desenvolvimento Embrionário/fisiologia , Receptores Notch/metabolismo , Transdução de Sinais/fisiologia
17.
Development ; 149(10)2022 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-35575387

RESUMO

The fibroblast growth factor (FGF) signalling pathway plays various roles during vertebrate embryogenesis, from mesoderm formation to brain patterning. This diversity of functions relies on the fact that vertebrates possess the largest FGF gene complement among metazoans. In the cephalochordate amphioxus, which belongs to the chordate clade together with vertebrates and tunicates, we have previously shown that the main role of FGF during early development is the control of rostral somite formation. Inhibition of this signalling pathway induces the loss of these structures, resulting in an embryo without anterior segmented mesoderm, as in the vertebrate head. Here, by combining several approaches, we show that the anterior presumptive paraxial mesoderm cells acquire an anterior axial fate when FGF signal is inhibited and that they are later incorporated in the anterior notochord. Our analysis of notochord formation in wild type and in embryos in which FGF signalling is inhibited also reveals that amphioxus anterior notochord presents transient prechordal plate features. Altogether, our results give insight into how changes in FGF functions during chordate evolution might have participated to the emergence of the complex vertebrate head.


Assuntos
Anfioxos , Somitos , Animais , Fatores de Crescimento de Fibroblastos/genética , Fatores de Crescimento de Fibroblastos/metabolismo , Regulação da Expressão Gênica no Desenvolvimento , Anfioxos/genética , Anfioxos/metabolismo , Mesoderma/metabolismo , Notocorda/metabolismo , Somitos/metabolismo , Vertebrados/metabolismo
18.
Dev Dyn ; 251(10): 1698-1710, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-35618666

RESUMO

BACKGROUND: The turtle carapace is an evolutionary novelty resulting from changes in the processes that build ribs and their associated muscles in most tetrapod species. Turtle embryos have several unique features that might play a role in this process, including the carapacial ridge, a Myf5 gene with shorter coding region that generates an alternative splice variant lacking exon 2, and unusual expression patterns of Lbx1 and HGF. RESULTS: We investigated these turtle-specific expression differences using genetic approaches in mouse embryos. At mid-gestation, mouse embryos producing Myf5 transcripts lacking exon 2 replicated some early properties of turtle somites, but still developed into viable and fertile mice. Extending Lbx1 expression into the hypaxial dermomyotomal lip of trunk somites to mimic the turtle Lbx1 expression pattern, produced fusions in the distal part of the ribs. CONCLUSIONS: Turtle-like Myf5 activity might generate a plastic state in developing trunk somites under which they can either enter carapace morphogenetic routes, possibly triggered by signals from the carapacial ridge, or still engage in the development of a standard tetrapod ribcage in the absence of those signals. In addition, trunk Lbx1 expression might play a later role in the formation of the lateral border of the carapace.


Assuntos
Tartarugas , Exoesqueleto , Animais , Evolução Biológica , Camundongos , Fator Regulador Miogênico 5/genética , Fator Regulador Miogênico 5/metabolismo , Plásticos/metabolismo , Somitos , Tartarugas/genética
19.
Elife ; 112022 05 06.
Artigo em Inglês | MEDLINE | ID: mdl-35522214

RESUMO

The dorsal axial muscles, or epaxial muscles, are a fundamental structure covering the spinal cord and vertebrae, as well as mobilizing the vertebrate trunk. To date, mechanisms underlying the morphogenetic process shaping the epaxial myotome are largely unknown. To address this, we used the medaka zic1/zic4-enhancer mutant Double anal fin (Da), which exhibits ventralized dorsal trunk structures resulting in impaired epaxial myotome morphology and incomplete coverage over the neural tube. In wild type, dorsal dermomyotome (DM) cells reduce their proliferative activity after somitogenesis. Subsequently, a subset of DM cells, which does not differentiate into the myotome population, begins to form unique large protrusions extending dorsally to guide the epaxial myotome dorsally. In Da, by contrast, DM cells maintain the high proliferative activity and mainly form small protrusions. By combining RNA- and ChIP-sequencing analyses, we revealed direct targets of Zic1, which are specifically expressed in dorsal somites and involved in various aspects of development, such as cell migration, extracellular matrix organization, and cell-cell communication. Among these, we identified wnt11 as a crucial factor regulating both cell proliferation and protrusive activity of DM cells. We propose that dorsal extension of the epaxial myotome is guided by a non-myogenic subpopulation of DM cells and that wnt11 empowers the DM cells to drive the coverage of the neural tube by the epaxial myotome.


Assuntos
Oryzias , Somitos , Proteínas Wnt/metabolismo , Animais , Desenvolvimento Embrionário , Regulação da Expressão Gênica no Desenvolvimento , Morfogênese
20.
Nature ; 605(7910): 516-521, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35477753

RESUMO

The body axis of vertebrate embryos is periodically segmented into bilaterally symmetric pairs of somites1,2. The anteroposterior length of somites, their position and left-right symmetry are thought to be molecularly determined before somite morphogenesis3,4. Here we show that, in zebrafish embryos, initial somite anteroposterior lengths and positions are imprecise and, consequently, many somite pairs form left-right asymmetrically. Notably, these imprecisions are not left unchecked and we find that anteroposterior lengths adjust within an hour after somite formation, thereby increasing morphological symmetry. We find that anteroposterior length adjustments result entirely from changes in somite shape without change in somite volume, with changes in anteroposterior length being compensated by corresponding changes in mediolateral length. The anteroposterior adjustment mechanism is facilitated by somite surface tension, which we show by comparing in vivo experiments and in vitro single-somite explant cultures using a mechanical model. Length adjustment is inhibited by perturbation of molecules involved in surface tension, such as integrin and fibronectin. By contrast, the adjustment mechanism is unaffected by perturbations to the segmentation clock, therefore revealing a distinct process that influences morphological segment lengths. We propose that tissue surface tension provides a general mechanism to adjust shapes and ensure precision and symmetry of tissues in developing embryos.


Assuntos
Somitos , Peixe-Zebra , Animais , Padronização Corporal , Desenvolvimento Embrionário , Morfogênese , Tensão Superficial , Proteínas de Peixe-Zebra/genética
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