An official website of the United States government
Markers for the endoderm and mesoderm germ layers are commonly expressed together in the early embryo, potentially reflecting cells’ ability to explore potential fates before fully committing. It remains unclear when commitment to a single-germ layer is reached and how it is impacted by external signals. Here, we address this important question in Drosophila , a convenient model system in which mesodermal and endodermal fates are associated with distinct cellular movements during gastrulation. Systematically applying endoderm-inducing extracellular signal-regulated kinase (ERK) signals to the ventral medial embryo—which normally only receives a mesoderm-inducing cue—reveals a critical time window during which mesodermal cell movements and gene expression are suppressed by proendoderm signaling. We identify the ERK target gene huckebein ( hkb ) as the main cause of the ventral furrow suppression and use computational modeling to show that Hkb repression of the mesoderm-associated gene snail is sufficient to account for a broad range of transcriptional and morphogenetic effects. Our approach, pairing precise signaling perturbations with observation of transcriptional dynamics and cell movements, provides a general framework for dissecting the complexities of combinatorial tissue patterning.
more »
« less
Putting in the Erk: Growth factor signaling and mesoderm morphogenesis
It has long been known that FGF signaling contributes to mesoderm formation, a germ layer found in triploblasts that is composed of highly migratory cells that give rise to muscles and to the skeletal structures of vertebrates. FGF signaling activates several pathways in the developing mesoderm, including transient activation of the Erk pathway, which triggers mesodermal fate specification through the induction of the gene brachyury and activates morphogenetic programs that allow mesodermal cells to position themselves in the embryo. In this review, we discuss what is known about the generation and interpretation of transient Erk signaling in mesodermal tissues across species. We focus specifically on mechanisms that translate the level and duration of Erk signaling into cell fate and cell movement instructions and discuss strategies for further interrogating the role that Erk signaling dynamics play in mesodermal gastrulation and morphogenesis.
more »
« less
- Award ID(s):
- 1750663
- PAR ID:
- 10436461
- Editor(s):
- Soriano, Phillippe M.
- Date Published:
- Journal Name:
- Current Topics in Developmental Biology
- Volume:
- 149
- ISSN:
- 0070-2153
- Page Range / eLocation ID:
- 263-310
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
More Like this
-
-
Abstract A fundamental goal in the organogenesis field is to understand how cells organize into tubular shapes. Toward this aim, we have established the hydro-vascular organ in the sea starPatiria miniataas a model for tubulogenesis. In this animal, bilateral tubes grow out from the tip of the developing gut, and precisely extend to specific sites in the larva. This growth involves cell migration coupled with mitosis in distinct zones. Cell proliferation requires FGF signaling, whereas the three-dimensional orientation of the organ depends on Wnt signaling. Specification and maintenance of tube cell fate requires Delta/Notch signaling. Moreover, we identify target genes of the FGF pathway that contribute to tube morphology, revealing molecular mechanisms for tube outgrowth. Finally, we report that FGF activates the Six1/2 transcription factor, which serves as an evolutionarily ancient regulator of branching morphogenesis. This study uncovers distinct mechanisms of tubulogenesis in vivo and we propose that cellular dynamics in the sea star hydro-vascular organ represents a key comparison for understanding the evolution of vertebrate organs.more » « less
-
Crosstalk between ERK and MRTF‐A signaling regulates TGFβ1‐induced epithelial‐mesenchymal transitionAbstract Epithelial‐mesenchymal transition (EMT) is a physiological process that is essential during embryogenesis and wound healing and also contributes to pathologies including fibrosis and cancer. EMT is characterized by marked gene expression changes, loss of cell–cell contacts, remodeling of the cytoskeleton, and acquisition of enhanced motility. In the late stages of EMT, cells can exhibit myofibroblast‐like properties with enhanced expression of the mesenchymal protein marker α‐smooth muscle actin and contractile activity. Transforming growth factor (TGF)‐β1 is a well‐known inducer of EMT and it activates a plethora of signaling cascades including extracellular signal‐regulated kinase (ERK). Previous reports have demonstrated a role for ERK signaling in the early stages of EMT, but the molecular impacts of ERK signaling on the late stages of EMT are still unknown. Here, we found that inhibition of the phosphorylation of ERK enhances focal adhesions, stress fiber formation, cell contractility, and gene expression changes associated with TGFβ1‐induced EMT in mammary epithelial cells. These effects are mediated in part by the phosphorylation state and subcellular localization of myocardin‐related transcription factor‐A. These findings indicate that the intricate crosstalk between signaling cascades plays an important role in regulating the progression of EMT and suggests new approaches to control EMT processes.more » « less
-
ABSTRACT Many developmental processes rely on the localized activation of receptor tyrosine kinases and their canonical downstream effectors Erk and Akt, yet the specific roles played by each of these signals is still poorly understood. Gastruloids, 3D cell culture models of mammalian gastrulation and axial elongation, enable quantitative dissection of signaling patterns and cell responses in a simplified, experimentally accessible context. We find that mouse gastruloids contain posterior-to-anterior gradients of Erk and Akt phosphorylation induced by distinct receptor tyrosine kinases, with features of the Erk pattern and expression of its downstream target Snail exhibiting hallmarks of size-invariant scaling. Both Erk and Akt signaling contribute to cell proliferation, whereas Erk activation is also sufficient to induce Snail expression and precipitate profound tissue shape changes. We further uncover that Erk signaling is sufficient to convert the entire gastruloid to one of two mesodermal fates depending on position along the anteroposterior axis. In all, these data demonstrate functional roles for two core signaling gradients in mammalian development and suggest how these modules might be harnessed to engineer user-defined tissues with predictable shapes and cell fates.more » « less
-
For decades it has been established that head muscle development differs from trunk muscle development. Similarly known, even though not in such detail, is that different subgroups of head muscles develop dependent on different underlying gene regulatory networks. Even less well studied are the tissue interactions during the developmental processes. Muscles derived from pharyngeal arch mesoderm depend on interactions with endoderm and neural crest cells, and, to a minor extent, ectodermal cues. Extraocular eye muscles respond to a mix of signals from surrounding mesoderm, but also neural crest cells; however, they are independent of endodermal cues. Head muscles derived from occipital paraxial mesoderm depend on tissue interactions similar to pharyngeal arch muscles but have a different migration trajectory. While the pharyngeal arch mesodermal cells and neural crest cells largely migrate from dorsal to ventral, the occipital paraxial mesodermal cells migrate from dorsal to ventral and from posterior to anterior. During the migration these cells proliferate and even start to differentiate, while pharyngeal mesodermal cells begin the differentiation process after reaching their respective pharyngeal arches. Here we present an overview of tissue interactions during the development of different head muscle populations, highlighting general concepts and main differences. Topic Category: Neural Crest, Placodes and Craniofacial Development Keywords: Craniofacial muscles, Myogenesis Funding or Support Information: NSF #2000005 to JMZCmore » « less
- Free Publicly Accessible Full Text
-
Accepted Manuscript1.0
- Journal Article:
- https://doi.org/10.1016/bs.ctdb.2022.02.007
