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1.
Nat Rev Mol Cell Biol ; 22(4): 245-265, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33483696

RESUMO

How the shape of embryos and organs emerges during development is a fundamental question that has fascinated scientists for centuries. Tissue dynamics arise from a small set of cell behaviours, including shape changes, cell contact remodelling, cell migration, cell division and cell extrusion. These behaviours require control over cell mechanics, namely active stresses associated with protrusive, contractile and adhesive forces, and hydrostatic pressure, as well as material properties of cells that dictate how cells respond to active stresses. In this Review, we address how cell mechanics and the associated cell behaviours are robustly organized in space and time during tissue morphogenesis. We first outline how not only gene expression and the resulting biochemical cues, but also mechanics and geometry act as sources of morphogenetic information to ultimately define the time and length scales of the cell behaviours driving morphogenesis. Next, we present two idealized modes of how this information flows - how it is read out and translated into a biological effect - during morphogenesis. The first, akin to a programme, follows deterministic rules and is hierarchical. The second follows the principles of self-organization, which rests on statistical rules characterizing the system's composition and configuration, local interactions and feedback. We discuss the contribution of these two modes to the mechanisms of four very general classes of tissue deformation, namely tissue folding and invagination, tissue flow and extension, tissue hollowing and, finally, tissue branching. Overall, we suggest a conceptual framework for understanding morphogenetic information that encapsulates genetics and biochemistry as well as mechanics and geometry as information modules, and the interplay of deterministic and self-organized mechanisms of their deployment, thereby diverging considerably from the traditional notion that shape is fully encoded and determined by genes.


Assuntos
Morfogênese/genética , Animais , Fenômenos Bioquímicos/genética , Fenômenos Biomecânicos/genética , Expressão Gênica/genética , Humanos
2.
Nature ; 634(8035): 919-928, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39415005

RESUMO

The prevailing dogma for morphological patterning in developing organisms argues that the combined inputs of transcription factor networks and signalling morphogens alone generate spatially and temporally distinct expression patterns. However, metabolism has also emerged as a critical developmental regulator1-10, independent of its functions in energy production and growth. The mechanistic role of nutrient utilization in instructing cellular programmes to shape the in vivo developing mammalian embryo remains unknown. Here we reveal two spatially resolved, cell-type- and stage-specific waves of glucose metabolism during mammalian gastrulation by using single-cell-resolution quantitative imaging of developing mouse embryos, stem cell models and embryo-derived tissue explants. We identify that the first spatiotemporal wave of glucose metabolism occurs through the hexosamine biosynthetic pathway to drive fate acquisition in the epiblast, and the second wave uses glycolysis to guide mesoderm migration and lateral expansion. Furthermore, we demonstrate that glucose exerts its influence on these developmental processes through cellular signalling pathways, with distinct mechanisms connecting glucose with the ERK activity in each wave. Our findings underscore that-in synergy with genetic mechanisms and morphogenic gradients-compartmentalized cellular metabolism is integral in guiding cell fate and specialized functions during development. This study challenges the view of the generic and housekeeping nature of cellular metabolism, offering valuable insights into its roles in various developmental contexts.


Assuntos
Embrião de Mamíferos , Gastrulação , Glucose , Análise de Célula Única , Animais , Feminino , Masculino , Camundongos , Linhagem da Célula , Movimento Celular , Embrião de Mamíferos/citologia , Embrião de Mamíferos/embriologia , Embrião de Mamíferos/metabolismo , Gastrulação/genética , Camadas Germinativas/metabolismo , Camadas Germinativas/citologia , Glucose/metabolismo , Glicólise , Hexosaminas/metabolismo , Hexosaminas/biossíntese , Mesoderma/metabolismo , Mesoderma/citologia , Mesoderma/embriologia , Vias Biossintéticas , Transdução de Sinais , Morfogênese/genética , MAP Quinases Reguladas por Sinal Extracelular/metabolismo
3.
Annu Rev Genet ; 55: 209-233, 2021 11 23.
Artigo em Inglês | MEDLINE | ID: mdl-34460295

RESUMO

Multicellular organisms develop complex shapes from much simpler, single-celled zygotes through a process commonly called morphogenesis. Morphogenesis involves an interplay between several factors, ranging from the gene regulatory networks determining cell fate and differentiation to the mechanical processes underlying cell and tissue shape changes. Thus, the study of morphogenesis has historically been based on multidisciplinary approaches at the interface of biology with physics and mathematics. Recent technological advances have further improved our ability to study morphogenesis by bridging the gap between the genetic and biophysical factors through the development of new tools for visualizing, analyzing, and perturbing these factors and their biochemical intermediaries. Here, we review how a combination of genetic, microscopic, biophysical, and biochemical approaches has aided our attempts to understand morphogenesis and discuss potential approaches that may be beneficial to such an inquiry in the future.


Assuntos
Morfogênese , Biofísica , Diferenciação Celular , Morfogênese/genética
4.
Nat Rev Genet ; 24(9): 610-626, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37095271

RESUMO

Major differences in facial morphology distinguish vertebrate species. Variation of facial traits underlies the uniqueness of human individuals, and abnormal craniofacial morphogenesis during development leads to birth defects that significantly affect quality of life. Studies during the past 40 years have advanced our understanding of the molecular mechanisms that establish facial form during development, highlighting the crucial roles in this process of a multipotent cell type known as the cranial neural crest cell. In this Review, we discuss recent advances in multi-omics and single-cell technologies that enable genes, transcriptional regulatory networks and epigenetic landscapes to be closely linked to the establishment of facial patterning and its variation, with an emphasis on normal and abnormal craniofacial morphogenesis. Advancing our knowledge of these processes will support important developments in tissue engineering, as well as the repair and reconstruction of the abnormal craniofacial complex.


Assuntos
Crista Neural , Qualidade de Vida , Humanos , Morfogênese/genética , Crista Neural/metabolismo , Epigênese Genética
5.
Nat Rev Mol Cell Biol ; 18(6): 375-388, 2017 06.
Artigo em Inglês | MEDLINE | ID: mdl-28293032

RESUMO

Planar cell polarity (PCP) is an essential feature of animal tissues, whereby distinct polarity is established within the plane of a cell sheet. Tissue-wide establishment of PCP is driven by multiple global cues, including gradients of gene expression, gradients of secreted WNT ligands and anisotropic tissue strain. These cues guide the dynamic, subcellular enrichment of PCP proteins, which can self-assemble into mutually exclusive complexes at opposite sides of a cell. Endocytosis, endosomal trafficking and degradation dynamics of PCP components further regulate planar tissue patterning. This polarization propagates throughout the whole tissue, providing a polarity axis that governs collective morphogenetic events such as the orientation of subcellular structures and cell rearrangements. Reflecting the necessity of polarized cellular behaviours for proper development and function of diverse organs, defects in PCP have been implicated in human pathologies, most notably in severe birth defects.


Assuntos
Polaridade Celular/fisiologia , Animais , Polaridade Celular/genética , Humanos , Morfogênese/genética , Morfogênese/fisiologia , Transporte Proteico/genética , Transporte Proteico/fisiologia , Transdução de Sinais/genética , Transdução de Sinais/fisiologia
6.
Nat Rev Mol Cell Biol ; 17(2): 97-109, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26726037

RESUMO

Collective cell migration has a key role during morphogenesis and during wound healing and tissue renewal in the adult, and it is involved in cancer spreading. In addition to displaying a coordinated migratory behaviour, collectively migrating cells move more efficiently than if they migrated separately, which indicates that a cellular interplay occurs during collective cell migration. In recent years, evidence has accumulated confirming the importance of such intercellular communication and exploring the molecular mechanisms involved. These mechanisms are based both on direct physical interactions, which coordinate the cellular responses, and on the collective cell behaviour that generates an optimal environment for efficient directed migration. The recent studies have described how leader cells at the front of cell groups drive migration and have highlighted the importance of follower cells and cell-cell communication, both between followers and between follower and leader cells, to improve the efficiency of collective movement.


Assuntos
Comunicação Celular , Movimento Celular , Proteínas da Matriz Extracelular/genética , Morfogênese/genética , Invasividade Neoplásica/genética , Citoesqueleto de Actina/genética , Citoesqueleto de Actina/metabolismo , Junções Aderentes/metabolismo , Junções Aderentes/ultraestrutura , Animais , Polaridade Celular , Proteínas da Matriz Extracelular/metabolismo , Regulação da Expressão Gênica , Humanos , Transdução de Sinais , Cicatrização/genética , Proteínas rac1 de Ligação ao GTP/genética , Proteínas rac1 de Ligação ao GTP/metabolismo
7.
Development ; 151(2)2024 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-38108472

RESUMO

Nerves play important roles in organ development and tissue homeostasis. Stem/progenitor cells differentiate into different cell lineages responsible for building the craniofacial organs. The mechanism by which nerves regulate stem/progenitor cell behavior in organ morphogenesis has not yet been comprehensively explored. Here, we use tooth root development in mouse as a model to investigate how sensory nerves regulate organogenesis. We show that sensory nerve fibers are enriched in the dental papilla at the initiation of tooth root development. Through single cell RNA-sequencing analysis of the trigeminal ganglion and developing molar, we reveal several signaling pathways that connect the sensory nerve with the developing molar, of which FGF signaling appears to be one of the important regulators. Fgfr2 is expressed in the progenitor cells during tooth root development. Loss of FGF signaling leads to shortened roots with compromised proliferation and differentiation of progenitor cells. Furthermore, Hh signaling is impaired in Gli1-CreER;Fgfr2fl/fl mice. Modulation of Hh signaling rescues the tooth root defects in these mice. Collectively, our findings elucidate the nerve-progenitor crosstalk and reveal the molecular mechanism of the FGF-SHH signaling cascade during tooth root morphogenesis.


Assuntos
Dente , Animais , Camundongos , Dente Molar , Morfogênese/genética , Odontogênese/genética , Raiz Dentária
8.
Development ; 151(6)2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38533736

RESUMO

How complex organs coordinate cellular morphogenetic events to achieve three-dimensional (3D) form is a central question in development. The question is uniquely tractable in the late Drosophila pupal retina, where cells maintain stereotyped contacts as they elaborate the specialized cytoskeletal structures that pattern the apical, basal and longitudinal planes of the epithelium. In this study, we combined cell type-specific genetic manipulation of the cytoskeletal regulator Abelson (Abl) with 3D imaging to explore how the distinct cellular morphogenetic programs of photoreceptors and interommatidial pigment cells (IOPCs) organize tissue pattern to support retinal integrity. Our experiments show that photoreceptor and IOPC terminal differentiation is unexpectedly interdependent, connected by an intercellular feedback mechanism that coordinates and promotes morphogenetic change across orthogonal tissue planes to ensure correct 3D retinal pattern. We propose that genetic regulation of specialized cellular differentiation programs combined with inter-plane mechanical feedback confers spatial coordination to achieve robust 3D tissue morphogenesis.


Assuntos
Proteínas de Drosophila , Drosophila , Animais , Drosophila melanogaster/genética , Proteínas de Drosophila/genética , Pupa , Retroalimentação , Retina , Morfogênese/genética
9.
Development ; 151(18)2024 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-39253748

RESUMO

Caenorhabditis elegans males undergo sex-specific tail tip morphogenesis (TTM) under the control of the DM-domain transcription factor DMD-3. To find genes regulated by DMD-3, we performed RNA-seq of laser-dissected tail tips. We identified 564 genes differentially expressed (DE) in wild-type males versus dmd-3(-) males and hermaphrodites. The transcription profile of dmd-3(-) tail tips is similar to that in hermaphrodites. For validation, we analyzed transcriptional reporters for 49 genes and found male-specific or male-biased expression for 26 genes. Only 11 DE genes overlapped with genes found in a previous RNAi screen for defective TTM. GO enrichment analysis of DE genes finds upregulation of genes within the unfolded protein response pathway and downregulation of genes involved in cuticle maintenance. Of the DE genes, 40 are transcription factors, indicating that the gene network downstream of DMD-3 is complex and potentially modular. We propose modules of genes that act together in TTM and are co-regulated by DMD-3, among them the chondroitin synthesis pathway and the hypertonic stress response.


Assuntos
Proteínas de Caenorhabditis elegans , Caenorhabditis elegans , Regulação da Expressão Gênica no Desenvolvimento , Morfogênese , RNA-Seq , Cauda , Animais , Caenorhabditis elegans/genética , Morfogênese/genética , Masculino , Proteínas de Caenorhabditis elegans/genética , Proteínas de Caenorhabditis elegans/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Redes Reguladoras de Genes , Especificidade de Órgãos/genética
10.
Development ; 151(8)2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38512712

RESUMO

The formation of complex three-dimensional organs during development requires precise coordination between patterning networks and mechanical forces. In particular, tissue folding is a crucial process that relies on a combination of local and tissue-wide mechanical forces. Here, we investigate the contribution of cell proliferation to epithelial morphogenesis using the Drosophila leg tarsal folds as a model. We reveal that tissue-wide compression forces generated by cell proliferation, in coordination with the Notch signaling pathway, are essential for the formation of epithelial folds in precise locations along the proximo-distal axis of the leg. As cell numbers increase, compressive stresses arise, promoting the folding of the epithelium and reinforcing the apical constriction of invaginating cells. Additionally, the Notch target dysfusion plays a key function specifying the location of the folds, through the apical accumulation of F-actin and the apico-basal shortening of invaginating cells. These findings provide new insights into the intricate mechanisms involved in epithelial morphogenesis, highlighting the crucial role of tissue-wide forces in shaping a three-dimensional organ in a reproducible manner.


Assuntos
Proliferação de Células , Proteínas de Drosophila , Drosophila , Receptores Notch , Animais , Drosophila/metabolismo , Drosophila melanogaster/metabolismo , Proteínas de Drosophila/genética , Proteínas de Drosophila/metabolismo , Epitélio/metabolismo , Morfogênese/genética , Transdução de Sinais , Receptores Notch/metabolismo
11.
Development ; 151(4)2024 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-38372390

RESUMO

Embryogenesis results from the coordinated activities of different signaling pathways controlling cell fate specification and morphogenesis. In vertebrate gastrulation, both Nodal and BMP signaling play key roles in germ layer specification and morphogenesis, yet their interplay to coordinate embryo patterning with morphogenesis is still insufficiently understood. Here, we took a reductionist approach using zebrafish embryonic explants to study the coordination of Nodal and BMP signaling for embryo patterning and morphogenesis. We show that Nodal signaling triggers explant elongation by inducing mesendodermal progenitors but also suppressing BMP signaling activity at the site of mesendoderm induction. Consistent with this, ectopic BMP signaling in the mesendoderm blocks cell alignment and oriented mesendoderm intercalations, key processes during explant elongation. Translating these ex vivo observations to the intact embryo showed that, similar to explants, Nodal signaling suppresses the effect of BMP signaling on cell intercalations in the dorsal domain, thus allowing robust embryonic axis elongation. These findings suggest a dual function of Nodal signaling in embryonic axis elongation by both inducing mesendoderm and suppressing BMP effects in the dorsal portion of the mesendoderm.


Assuntos
Padronização Corporal , Peixe-Zebra , Animais , Padronização Corporal/genética , Proteína Nodal/genética , Proteína Nodal/metabolismo , Morfogênese/genética , Transdução de Sinais , Fator de Crescimento Transformador beta/metabolismo , Proteínas de Peixe-Zebra/genética , Proteínas de Peixe-Zebra/metabolismo , Regulação da Expressão Gênica no Desenvolvimento
12.
Development ; 151(11)2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38752427

RESUMO

Bone morphogenic protein (BMP) signaling plays an essential and highly conserved role in embryo axial patterning in animal species. However, in mammalian embryos, which develop inside the mother, early development includes a preimplantation stage, which does not occur in externally developing embryos. During preimplantation, the epiblast is segregated from extra-embryonic lineages that enable implantation and development in utero. Yet, the requirement for BMP signaling is imprecisely defined in mouse early embryos. Here, we show that, in contrast to previous reports, BMP signaling (SMAD1/5/9 phosphorylation) is not detectable until implantation when it is detected in the primitive endoderm - an extra-embryonic lineage. Moreover, preimplantation development appears to be normal following deletion of maternal and zygotic Smad4, an essential effector of canonical BMP signaling. In fact, mice lacking maternal Smad4 are viable. Finally, we uncover a new requirement for zygotic Smad4 in epiblast scaling and cavitation immediately after implantation, via a mechanism involving FGFR/ERK attenuation. Altogether, our results demonstrate no role for BMP4/SMAD4 in the first lineage decisions during mouse development. Rather, multi-pathway signaling among embryonic and extra-embryonic cell types drives epiblast morphogenesis postimplantation.


Assuntos
Implantação do Embrião , Camadas Germinativas , Morfogênese , Proteína Smad4 , Animais , Feminino , Camundongos , Blastocisto/metabolismo , Blastocisto/citologia , Proteína Morfogenética Óssea 4/metabolismo , Proteína Morfogenética Óssea 4/genética , Implantação do Embrião/genética , Embrião de Mamíferos/metabolismo , Desenvolvimento Embrionário/genética , Endoderma/metabolismo , Endoderma/embriologia , Regulação da Expressão Gênica no Desenvolvimento , Camadas Germinativas/metabolismo , Camundongos Knockout , Morfogênese/genética , Transdução de Sinais , Proteína Smad4/metabolismo , Proteína Smad4/genética
13.
Development ; 151(8)2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38602485

RESUMO

Alveologenesis, the final stage in lung development, substantially remodels the distal lung, expanding the alveolar surface area for efficient gas exchange. Secondary crest myofibroblasts (SCMF) exist transiently in the neonatal distal lung and are crucial for alveologenesis. However, the pathways that regulate SCMF function, proliferation and temporal identity remain poorly understood. To address this, we purified SCMFs from reporter mice, performed bulk RNA-seq and found dynamic changes in Hippo-signaling components during alveologenesis. We deleted the Hippo effectors Yap/Taz from Acta2-expressing cells at the onset of alveologenesis, causing a significant arrest in alveolar development. Using single cell RNA-seq, we identified a distinct cluster of cells in mutant lungs with altered expression of marker genes associated with proximal mesenchymal cell types, airway smooth muscle and alveolar duct myofibroblasts. In vitro studies confirmed that Yap/Taz regulates myofibroblast-associated gene signature and contractility. Together, our findings show that Yap/Taz is essential for maintaining functional myofibroblast identity during postnatal alveologenesis.


Assuntos
Diferenciação Celular , Via de Sinalização Hippo , Morfogênese , Miofibroblastos , Proteínas Serina-Treonina Quinases , Alvéolos Pulmonares , Transdução de Sinais , Proteínas de Sinalização YAP , Animais , Camundongos , Miofibroblastos/metabolismo , Miofibroblastos/citologia , Proteínas de Sinalização YAP/metabolismo , Proteínas de Sinalização YAP/genética , Alvéolos Pulmonares/metabolismo , Alvéolos Pulmonares/citologia , Proteínas Serina-Treonina Quinases/metabolismo , Proteínas Serina-Treonina Quinases/genética , Morfogênese/genética , Mesoderma/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/genética , Pulmão/metabolismo , Organogênese/genética , Regulação da Expressão Gênica no Desenvolvimento
14.
Development ; 151(10)2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38738602

RESUMO

Visual circuit development is characterized by subdivision of neuropils into layers that house distinct sets of synaptic connections. We find that, in the Drosophila medulla, this layered organization depends on the axon guidance regulator Plexin A. In Plexin A null mutants, synaptic layers of the medulla neuropil and arborizations of individual neurons are wider and less distinct than in controls. Analysis of semaphorin function indicates that Semaphorin 1a, acting in a subset of medulla neurons, is the primary partner for Plexin A in medulla lamination. Removal of the cytoplasmic domain of endogenous Plexin A has little effect on the formation of medulla layers; however, both null and cytoplasmic domain deletion mutations of Plexin A result in an altered overall shape of the medulla neuropil. These data suggest that Plexin A acts as a receptor to mediate morphogenesis of the medulla neuropil, and as a ligand for Semaphorin 1a to subdivide it into layers. Its two independent functions illustrate how a few guidance molecules can organize complex brain structures by each playing multiple roles.


Assuntos
Proteínas de Drosophila , Morfogênese , Proteínas do Tecido Nervoso , Neurópilo , Lobo Óptico de Animais não Mamíferos , Receptores de Superfície Celular , Semaforinas , Animais , Proteínas de Drosophila/metabolismo , Proteínas de Drosophila/genética , Semaforinas/metabolismo , Semaforinas/genética , Proteínas do Tecido Nervoso/metabolismo , Proteínas do Tecido Nervoso/genética , Morfogênese/genética , Neurópilo/metabolismo , Lobo Óptico de Animais não Mamíferos/metabolismo , Lobo Óptico de Animais não Mamíferos/embriologia , Receptores de Superfície Celular/metabolismo , Receptores de Superfície Celular/genética , Drosophila melanogaster/metabolismo , Drosophila melanogaster/genética , Drosophila melanogaster/embriologia , Neurônios/metabolismo , Drosophila/metabolismo , Drosophila/embriologia , Mutação/genética
15.
Development ; 151(19)2024 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-39258889

RESUMO

Pharyngeal endoderm cells undergo convergence and extension (C&E), which is essential for endoderm pouch formation and craniofacial development. Our previous work implicates Gα13/RhoA-mediated signaling in regulating this process, but the underlying mechanisms remain unclear. Here, we have used endoderm-specific transgenic and Gα13 mutant zebrafish to demonstrate that Gα13 plays a crucial role in pharyngeal endoderm C&E by regulating RhoA activation and E-cadherin expression. We showed that during C&E, endodermal cells gradually establish stable cell-cell contacts, acquire apical-basal polarity and undergo actomyosin-driven apical constriction, which are processes that require Gα13. Additionally, we found that Gα13-deficient embryos exhibit reduced E-cadherin expression, partially contributing to endoderm C&E defects. Notably, interfering with RhoA function disrupts spatial actomyosin activation without affecting E-cadherin expression. Collectively, our findings identify crucial cellular processes for pharyngeal endoderm C&E and reveal that Gα13 controls this through two independent pathways - modulating RhoA activation and regulating E-cadherin expression - thus unveiling intricate mechanisms governing pharyngeal endoderm morphogenesis.


Assuntos
Caderinas , Endoderma , Subunidades alfa G12-G13 de Proteínas de Ligação ao GTP , Regulação da Expressão Gênica no Desenvolvimento , Faringe , Proteínas de Peixe-Zebra , Peixe-Zebra , Proteína rhoA de Ligação ao GTP , Animais , Endoderma/metabolismo , Endoderma/embriologia , Endoderma/citologia , Caderinas/metabolismo , Caderinas/genética , Peixe-Zebra/embriologia , Peixe-Zebra/metabolismo , Peixe-Zebra/genética , Proteína rhoA de Ligação ao GTP/metabolismo , Proteína rhoA de Ligação ao GTP/genética , Proteínas de Peixe-Zebra/metabolismo , Proteínas de Peixe-Zebra/genética , Subunidades alfa G12-G13 de Proteínas de Ligação ao GTP/metabolismo , Subunidades alfa G12-G13 de Proteínas de Ligação ao GTP/genética , Faringe/embriologia , Faringe/metabolismo , Actomiosina/metabolismo , Transdução de Sinais , Morfogênese/genética , Polaridade Celular , Animais Geneticamente Modificados , Embrião não Mamífero/metabolismo
16.
Plant Cell ; 36(2): 324-345, 2024 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-37804091

RESUMO

Floral homeotic MADS-box transcription factors ensure the correct morphogenesis of floral organs, which are organized in different cell layers deriving from distinct meristematic layers. How cells from these distinct layers acquire their respective identities and coordinate their growth to ensure normal floral organ morphogenesis is unresolved. Here, we studied petunia (Petunia × hybrida) petals that form a limb and tube through congenital fusion. We identified petunia mutants (periclinal chimeras) expressing the B-class MADS-box gene DEFICIENS in the petal epidermis or in the petal mesophyll, called wico and star, respectively. Strikingly, wico flowers form a strongly reduced tube while their limbs are almost normal, while star flowers form a normal tube but greatly reduced and unpigmented limbs, showing that petunia petal morphogenesis is highly modular. These mutants highlight the layer-specific roles of PhDEF during petal development. We explored the link between PhDEF and petal pigmentation, a well-characterized limb epidermal trait. The anthocyanin biosynthesis pathway was strongly downregulated in star petals, including its major regulator ANTHOCYANIN2 (AN2). We established that PhDEF directly binds to the AN2 terminator in vitro and in vivo, suggesting that PhDEF might regulate AN2 expression and therefore petal epidermis pigmentation. Altogether, we show that cell layer-specific homeotic activity in petunia petals differently impacts tube and limb development, revealing the relative importance of the different cell layers in the modular architecture of petunia petals.


Assuntos
Petunia , Fatores de Transcrição , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Petunia/genética , Petunia/metabolismo , Proteínas de Plantas/metabolismo , Regulação da Expressão Gênica , Flores/fisiologia , Morfogênese/genética , Regulação da Expressão Gênica de Plantas/genética
17.
Plant Cell ; 36(5): 1755-1776, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38318972

RESUMO

The milestone of compound leaf development is the generation of separate leaflet primordia during the early stages, which involves two linked but distinct morphogenetic events: leaflet initiation and boundary establishment for leaflet separation. Although some progress in understanding the regulatory pathways for each event have been made, it is unclear how they are intrinsically coordinated. Here, we identify the PINNATE-LIKE PENTAFOLIATA2 (PINNA2) gene encoding a newly identified GRAS transcription factor in Medicago truncatula. PINNA2 transcripts are preferentially detected at organ boundaries. Its loss-of-function mutations convert trifoliate leaves into a pinnate pentafoliate pattern. PINNA2 directly binds to the promoter region of the LEAFY orthologue SINGLE LEAFLET1 (SGL1), which encodes a key positive regulator of leaflet initiation, and downregulates its expression. Further analysis revealed that PINNA2 synergizes with two other repressors of SGL1 expression, the BEL1-like homeodomain protein PINNA1 and the C2H2 zinc finger protein PALMATE-LIKE PENTAFOLIATA1 (PALM1), to precisely define the spatiotemporal expression of SGL1 in compound leaf primordia, thereby maintaining a proper pattern of leaflet initiation. Moreover, we showed that the enriched expression of PINNA2 at the leaflet-to-leaflet boundaries is positively regulated by the boundary-specific gene MtNAM, which is essential for leaflet boundary formation. Together, these results unveil a pivotal role of the boundary-expressed transcription factor PINNA2 in regulating leaflet initiation, providing molecular insights into the coordination of intricate developmental processes underlying compound leaf pattern formation.


Assuntos
Regulação da Expressão Gênica de Plantas , Medicago truncatula , Folhas de Planta , Medicago truncatula/genética , Medicago truncatula/crescimento & desenvolvimento , Medicago truncatula/metabolismo , Morfogênese/genética , Folhas de Planta/genética , Folhas de Planta/crescimento & desenvolvimento , Folhas de Planta/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Plantas Geneticamente Modificadas , Regiões Promotoras Genéticas/genética , Fatores de Transcrição/metabolismo , Fatores de Transcrição/genética
18.
Plant Cell ; 36(6): 2375-2392, 2024 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-38470570

RESUMO

Homeodomain (HD) proteins regulate embryogenesis in animals such as the fruit fly (Drosophila melanogaster), often in a concentration-dependent manner. HD-leucine zipper (Zip) IV family genes are unique to plants and often function in the L1 epidermal cell layer. However, our understanding of the roles of HD-Zip IV family genes in plant morphogenesis is limited. In this study, we investigated the morphogenesis of tomato (Solanum lycopersicum) multicellular trichomes, a type of micro-organ in plants. We found that a gradient of the HD-Zip IV regulator Woolly (Wo) coordinates spatially polarized cell division and cell expansion in multicellular trichomes. Moreover, we identified a TEOSINTE BRANCHED1, CYCLOIDEA, and PROLIFERATING CELL NUCLEAR ANTIGEN BINDING FACTOR (TCP) transcription factor-encoding gene, SlBRANCHED2a (SlBRC2a), as a key downstream target of Wo that regulates the transition from cell division to cell expansion. High levels of Wo promote cell division in apical trichome cells, whereas in basal trichome cells, Wo mediates a negative feedback loop with SlBRC2a that forces basal cells to enter endoreduplication. The restricted high and low activities of Wo pattern the morphogenesis of tomato multicellular trichomes. These findings provide insights into the functions of HD-Zip IV genes during plant morphogenesis.


Assuntos
Regulação da Expressão Gênica de Plantas , Morfogênese , Proteínas de Plantas , Solanum lycopersicum , Tricomas , Solanum lycopersicum/genética , Solanum lycopersicum/crescimento & desenvolvimento , Solanum lycopersicum/metabolismo , Solanum lycopersicum/citologia , Tricomas/crescimento & desenvolvimento , Tricomas/genética , Tricomas/metabolismo , Proteínas de Plantas/metabolismo , Proteínas de Plantas/genética , Morfogênese/genética , Proteínas de Homeodomínio/metabolismo , Proteínas de Homeodomínio/genética , Fatores de Transcrição/metabolismo , Fatores de Transcrição/genética , Divisão Celular
19.
PLoS Biol ; 22(8): e3002762, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39173068

RESUMO

During embryonic development, tissues and organs are gradually shaped into their functional morphologies through a series of spatiotemporally tightly orchestrated cell behaviors. A highly conserved organ shape across metazoans is the epithelial tube. Tube morphogenesis is a complex multistep process of carefully choreographed cell behaviors such as convergent extension, cell elongation, and lumen formation. The identity of the signaling molecules that coordinate these intricate morphogenetic steps remains elusive. The notochord is an essential tubular organ present in the embryonic midline region of all members of the chordate phylum. Here, using genome editing, pharmacology and quantitative imaging in the early chordate Ciona intestinalis we show that Ano10/Tmem16k, a member of the evolutionarily ancient family of transmembrane proteins called Anoctamin/TMEM16 is essential for convergent extension, lumen expansion, and connection during notochord morphogenesis. We find that Ano10/Tmem16k works in concert with the plasma membrane (PM) localized Na+/Ca2+ exchanger (NCX) and the endoplasmic reticulum (ER) residing SERCA, RyR, and IP3R proteins to establish developmental stage specific Ca2+ signaling molecular modules that regulate notochord morphogenesis and Ca2+ dynamics. In addition, we find that the highly conserved Ca2+ sensors calmodulin (CaM) and Ca2+/calmodulin-dependent protein kinase (CaMK) show an Ano10/Tmem16k-dependent subcellular localization. Their pharmacological inhibition leads to convergent extension, tubulogenesis defects, and deranged Ca2+ dynamics, suggesting that Ano10/Tmem16k is involved in both the "encoding" and "decoding" of developmental Ca2+ signals. Furthermore, Ano10/Tmem16k mediates cytoskeletal reorganization during notochord morphogenesis, likely by altering the localization of 2 important cytoskeletal regulators, the small GTPase Ras homolog family member A (RhoA) and the actin binding protein Cofilin. Finally, we use electrophysiological recordings and a scramblase assay in tissue culture to demonstrate that Ano10/Tmem16k likely acts as an ion channel but not as a phospholipid scramblase. Our results establish Ano10/Tmem16k as a novel player in the prevertebrate molecular toolkit that controls organ morphogenesis across scales.


Assuntos
Anoctaminas , Ciona intestinalis , Morfogênese , Notocorda , Animais , Notocorda/metabolismo , Notocorda/embriologia , Anoctaminas/metabolismo , Anoctaminas/genética , Ciona intestinalis/metabolismo , Ciona intestinalis/embriologia , Ciona intestinalis/genética , Morfogênese/genética , Sinalização do Cálcio , Regulação da Expressão Gênica no Desenvolvimento , Retículo Endoplasmático/metabolismo , Cálcio/metabolismo
20.
PLoS Genet ; 20(7): e1011330, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-39083711

RESUMO

Coordinated activation and inhibition of F-actin supports the movements of morphogenesis. Understanding the proteins that regulate F-actin is important, since these proteins are mis-regulated in diseases like cancer. Our studies of C. elegans embryonic epidermal morphogenesis identified the GTPase CED-10/Rac1 as an essential activator of F-actin. However, we need to identify the GEF, or Guanine-nucleotide Exchange Factor, that activates CED-10/Rac1 during embryonic cell migrations. The two-component GEF, CED-5/CED-12, is known to activate CED-10/Rac1 to promote cell movements that result in the engulfment of dying cells during embryogenesis, and a later cell migration of the larval Distal Tip Cell. It is believed that CED-5/CED-12 powers cellular movements of corpse engulfment and DTC migration by promoting F-actin formation. Therefore, we tested if CED-5/CED-12 was involved in embryonic migrations, and got a contradictory result. CED-5/CED-12 definitely support embryonic migrations, since their loss led to embryos that died due to failed epidermal cell migrations. However, CED-5/CED-12 inhibited F-actin in the migrating epidermis, the opposite of what was expected for a CED-10 GEF. To address how CED-12/CED-5 could have two opposing effects on F-actin, during corpse engulfment and cell migration, we investigated if CED-12 harbors GAP (GTPase Activating Protein) functions. A candidate GAP region in CED-12 faces away from the CED-5 GEF catalytic region. Mutating a candidate catalytic Arginine in the CED-12 GAP region (R537A) altered the epidermal cell migration function, and not the corpse engulfment function. We interfered with GEF function by interfering with CED-5's ability to bind Rac1/CED-10. Mutating Serine-Arginine in CED-5/DOCK predicted to bind and stabilize Rac1 for catalysis, resulted in loss of both ventral enclosure and corpse engulfment. Genetic and expression studies strongly support that the GAP function likely acts on different GTPases. Thus, we propose CED-5/CED-12 support the cycling of multiple GTPases, by using distinct domains, to both promote and inhibit F-actin nucleation.


Assuntos
Actinas , Proteínas de Caenorhabditis elegans , Caenorhabditis elegans , Movimento Celular , Animais , Actinas/metabolismo , Motivos de Aminoácidos , Caenorhabditis elegans/genética , Caenorhabditis elegans/metabolismo , Proteínas de Caenorhabditis elegans/metabolismo , Proteínas de Caenorhabditis elegans/genética , Epiderme/metabolismo , Fatores de Troca do Nucleotídeo Guanina/metabolismo , Fatores de Troca do Nucleotídeo Guanina/genética , Morfogênese/genética , Proteínas rac1 de Ligação ao GTP/metabolismo , Proteínas rac1 de Ligação ao GTP/genética
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