Editing Invagination (section)

== Notable examples ==

=== ''Drosophila'' ventral furrow ===
[[File:Ventral_furrow_formation_in_drosophila_embryo.png|thumb|426x426px|Formation of the ventral furrow in a ''Drosophila'' embryo. Cell nuclei (blue), membranes (green), and myosin (red) are stained.]]
One of the most well studied models of invagination is the ventral furrow in ''Drosophila melanogaster''. The formation of this structure is one of the first major cell movements in ''Drosophila'' gastrulation. In this process, the prospective [[mesoderm]]––the region of cells along the [[Anatomical terms of location|ventral]] midline of the embryo––folds inwards to form the ventral furrow. This furrow eventually pinches off and becomes a tube inside the embryo and ultimately flattens to form a layer of tissue underneath the ventral surface.<ref name=":6">{{Cite book |last=Gilbert |first=Scott F. |url=https://www.ncbi.nlm.nih.gov/books/NBK9983/ |title=Developmental Biology |last2=Gilbert |first2=Scott F. |date=2000 |publisher=Sinauer Associates |isbn=978-0-87893-243-6 |edition=6th}}</ref>

Ventral furrow formation is driven by apical constriction of the future mesoderm cells, which first flatten along the apical surface and then contract their apical membranes. The classical models for how apical constriction worked in this context were based on the “purse-string” mechanism where an actin-myosin band around the circumference of the apical cell surface contracts.<ref name=":7">Gheisari, Elham, Mostafa Aakhte, and H. -Arno J. Müller. 2020. “Gastrulation in ''Drosophila Melanogaster'': Genetic Control, Cellular Basis and Biomechanics.” ''Mechanisms of Development'' 163 (September):103629. <nowiki>https://doi.org/10.1016/j.mod.2020.103629</nowiki>.</ref>  However, more recent investigations have revealed that, while there is a circumferential band of actin associated with cell junctions on the side of cells, it is actually an actin-myosin network arranged radially across the apical surface that powers apical constriction.<ref name=":8">Martin, Adam C., Matthias Kaschube, and Eric F. Wieschaus. 2009. “Pulsed Contractions of an Actin–Myosin Network Drive Apical Constriction.” ''Nature'' 457 (7228): 495–99. <nowiki>https://doi.org/10.1038/nature07522</nowiki>.</ref> This structure acts like a radial version of a muscle sarcomere.<ref name=":3" /> Force generated by myosin results in contraction towards the center of the cell. The cells do not contract continuously but rather have pulsed contractions. In between contractions, the actin network around the circumference of the cell helps stabilize the reduced size of the cell, allowing for a progressive decrease in size of the apical surface.<ref name=":8" /> In addition to apical constriction, adhesion between cells through adherens junctions is critical for transforming these individual cell-level contractions into a deformation of a whole tissue.

Genetically, formation of the ventral furrow relies on the activity of the [[Transcription factor|transcription factors]] ''[[Twist-related protein 1|twist]]'' and ''[[SNAI1|snail]]'', which are expressed in the prospective ventral mesoderm before furrow formation.<ref name=":7" /> Downstream of ''twist'' is the Fog signaling pathway, which controls the changes that occur in the apical domain of cells.<ref>Manning, Alyssa J., and Stephen L. Rogers. 2014. “The Fog Signaling Pathway: Insights into Signaling in Morphogenesis.” ''Developmental Biology'' 394 (1): 6–14. <nowiki>https://doi.org/10.1016/j.ydbio.2014.08.003</nowiki>.</ref>

=== Neural tube formation ===
{{main|Neurulation}}
[[File:Neural_tube_formation_in_mouse.jpg|thumb|462x462px|Cartoon of neural tube formation in a mouse embryo, showing the median hinge point and points of tissue buckling along the sides]]
Scientists have studied the process of neural tube formation in vertebrate embryos since the late 1800s.<ref name=":0" /> Across vertebrate groups including [[Amphibian|amphibians]], [[Reptile|reptiles]], [[Bird|birds]], and [[Mammal|mammals]], the neural tube (the embryonic precursor of the [[spinal cord]]) forms through the invagination of the neural plate into a tube, known as primary neurulation. In [[fish]] (and in some contexts in other vertebrates), the neural tube can also be formed by a non-invagination-mediated process known as secondary neurulation.<ref name=":6" /> While some differences exist in the mechanism of primary neurulation between vertebrate species, the general process is similar. Neurulation involves the formation of a medial hinge point at the middle of the neural plate, which is where tissue bending is initiated. The cells at the medial hinge point become wedge shaped. In some contexts, such as in ''[[Xenopus]]'' frog embryos, this cell shape change appears to be due to apical constriction.<ref>Nikolopoulou, Evanthia, Gabriel L. Galea, Ana Rolo, Nicholas D. E. Greene, and Andrew J. Copp. 2017. “Neural Tube Closure: Cellular, Molecular and Biomechanical Mechanisms.” ''Development'' 144 (4): 552–66. <nowiki>https://doi.org/10.1242/dev.145904</nowiki>.</ref><ref>Christodoulou, Neophytos, and Paris A. Skourides. 2015. “Cell-Autonomous Ca2+ Flashes Elicit Pulsed Contractions of an Apical Actin Network to Drive Apical Constriction during Neural Tube Closure.” ''Cell Reports'' 13 (10): 2189–2202. <nowiki>https://doi.org/10.1016/j.celrep.2015.11.017</nowiki>.</ref> However, in chickens and mice, bending at this hinge point is mediated by a process called basal wedging, rather than apical constriction.<ref name=":4" /><ref>Ybot-Gonzalez, Patricia, and Andrew J. Copp. 1999. “Bending of the Neural Plate during Mouse Spinal Neurulation Is Independent of Actin Microfilaments.” ''Developmental Dynamics'' 215 (3): 273–83. <nowiki>https://doi.org/10.1002/(SICI)1097-0177(199907)215:3</nowiki><273::AID-AJA9>3.0.CO;2-H.</ref><ref>Schoenwolf, Gary C., David Folsom, and Ardis Moe. 1988. “A Reexamination of the Role of Microfilaments in Neurulation in the Chick Embryo.” ''The Anatomical Record'' 220 (1): 87–102. <nowiki>https://doi.org/10.1002/ar.1092200111</nowiki>.</ref> In this case, the cells are so thin that the movement of the [[Cell nucleus|nucleus]] to the basal side of the cell causes a bulge in the basal part of the cell. This process may be regulated by how the cell divisions take place. Contractions of actin-myosin cables are also important for the invagination of the neural plate. Supracellular actin cables stretching across the neural plate help pull the tissue together (see {{Section link|2=Supracellular cables|nopage=yes}}). Furthermore, forces pushing into the neural plate from the adjacent tissue also may play a role in the folding of the neural plate.<ref>Suzuki, Makoto, Hitoshi Morita, and Naoto Ueno. 2012. “Molecular Mechanisms of Cell Shape Changes That Contribute to Vertebrate Neural Tube Closure.” ''DGD'' 54 (3): 266–76. <nowiki>https://doi.org/10.1111/j.1440-169X.2012.01346.x</nowiki>.</ref><ref>Morita, Hitoshi, Hiroko Kajiura-Kobayashi, Chiyo Takagi, Takamasa S. Yamamoto, Shigenori Nonaka, and Naoto Ueno. 2012. “Cell Movements of the Deep Layer of Non-Neural Ectoderm Underlie Complete Neural Tube Closure in Xenopus.” ''Development'' 139 (8): 1417–26. <nowiki>https://doi.org/10.1242/dev.073239</nowiki>.</ref><ref>Hackett, Deborah A., Jodi L. Smith, and Gary C. Schoenwolf. 1997. “Epidermal Ectoderm Is Required for Full Elevation and for Convergence during Bending of the Avian Neural Plate.” ''Developmental Dynamics'' 210 (4): 397–406. <nowiki>https://doi.org/10.1002/(SICI)1097-0177(199712)210:4</nowiki><397::AID-AJA4>3.0.CO;2-B.</ref>

=== Sea urchin gastrulation ===
[[File:Sea_urchin_gastrulation.png|left|thumb|175x175px|Invagination of the archenteron during sea urchin gastrulation]]
[[Sea urchin]] gastrulation is another classic model for invagination in embryology. One of the early gastrulation movements in sea urchins is the invagination of a region of cells at the [[Polarity in embryogenesis|vegetal]] side of the embryo (vegetal plate) to become the [[archenteron]], or future gut tube. There are multiple stages of archenteron invagination: a first stage where the initial folding in of tissue occurs, a second stage where the archenteron elongates, and in some species a third stage where the archenteron contacts the other side of the cell cavity and finishes its elongation.<ref name=":6" />

Apical constriction occurs in archenteron invagination, with a ring of cells called “bottle cells” in the center of the vegetal plate becoming wedge-shaped.<ref name=":9">Kimberly, Elizabeth Laxson, and Jeff Hardin. 1998. “Bottle Cells Are Required for the Initiation of Primary Invagination in the Sea Urchin Embryo.” ''Developmental Biology'' 204 (1): 235–50. <nowiki>https://doi.org/10.1006/dbio.1998.9075</nowiki>.</ref> However, invagination does not seem to be solely driven by the apical constriction of bottle cells, as inhibiting actin polymerization<ref name=":10">Lane, Mary Constance, M.A.R. Koehl, Fred Wilt, and Ray Keller. 1993. “A Role for Regulated Secretion of Apical Extracellular Matrix during Epithelial Invagination in the Sea Urchin.” ''Development'' 117 (3): 1049–60. <nowiki>https://doi.org/10.1242/dev.117.3.1049</nowiki>.</ref> or removing bottle cells does not fully block invagination.<ref name=":9" /> Several other mechanisms have been proposed to be involved in the process, including a role for extraembryonic [[extracellular matrix]].<ref>McClay, David R., Jacob Warner, Megan Martik, Esther Miranda, and Leslie Slota. 2020. “Chapter Seven - Gastrulation in the Sea Urchin.” In ''Current Topics in Developmental Biology'', edited by Lilianna Solnica-Krezel, 136:195–218. Gastrulation: From Embryonic Pattern to Form. Academic Press. <nowiki>https://doi.org/10.1016/bs.ctdb.2019.08.004</nowiki>.</ref> In this model, there are two layers of extracellular matrix at the apical surface of cells made of different proteins. When cells from the vegetal plate secrete a molecule ([[chondroitin sulfate proteoglycan]]) that is highly water absorbent into the inner layer, this causes the layer to swell, making the tissue buckle inwards.<ref name=":10" /> Several genetic pathways have been implicated in this process. [[Wnt signaling pathway|Wnt signaling]] through the non-canonical [[planar cell polarity]] pathway has been shown to be important, with one of its downstream targets being the small [[GTPase]] [[Transforming protein RhoA|RhoA]]. [[Fibroblast growth factor|FGF signaling]] also plays a role in invagination.<ref>Lyons, Deirdre C., Stacy L. Kaltenbach, and David R. McClay. 2012. “Morphogenesis in Sea Urchin Embryos: Linking Cellular Events to Gene Regulatory Network States.” ''WIREs Developmental Biology'' 1 (2): 231–52. <nowiki>https://doi.org/10.1002/wdev.18</nowiki>.</ref>

===''Amphioxus'' gastrulation===
[[File:Invagination.jpg|thumb|Invagination process in an amphioxus|337x337px]]
The invagination in ''[[amphioxus]]'' is the first cell movement of gastrulation. This process was first described by [[Edwin Conklin|Conklin]]. During gastrulation, the [[blastula]] will be transformed by the invagination. The [[endoderm]] folds towards the inner part and thus the [[blastocoel]] transforms into a cup-shaped structure with a double wall. The inner wall is now called the [[archenteron]]; the primitive gut. The archenteron will open to the exterior through the [[blastopore]]. The outer wall will become the [[ectoderm]], later forming the [[epidermis]] and [[nervous system]].<ref>{{cite book |last=Browder |first=Leon |date=1984 |title=Developmental Biology |location=Canada |publisher=CBS College Publishing |page=599 |isbn= 4833702010 }}</ref>

===Tunicate gastrulation===
In [[tunicates]], invagination is the first mechanism that takes place during gastrulation. The four largest [[endoderm]] cells induce the invagination process in the tunicates. Invagination consists of the internal movements of a sheet of cells (the endoderm) based on changes in their shape. The blastula of the tunicates is a little flattened in the [[vegetal pole]] making a change of shape from a columnar to a wedge shape. Once the endoderm cells were invaginated, the cells will keep moving beneath the ectoderm. Later, the blastopore will be formed and with this, the invagination process is complete. The blastopore will be surrounded by the [[mesoderm]] by all sides.<ref name="Sinauer Associates Inc">{{cite book |last1=Gilbert |first1=Scott |url=https://archive.org/details/embryologyconstr0000unse |title=Embryology, Constructing the Organism |last2=Rauno |first2=Anne |date=1997 |publisher=Sinauer Associates |isbn=0-87893-237-2 |location=Sunderland, Massachusetts |language=en |url-access=registration}}</ref>