Cleavage : The Fundamental Stages of Early Embryonic Development

 I. Introduction to Early Embryonic Development

Early embryonic development represents the remarkable journey from a single fertilized egg, or zygote, to a complex multicellular organism with a rudimentary body plan. This initial phase is characterized by a series of rapid and precisely orchestrated cellular transformations that lay the indispensable groundwork for all subsequent growth, differentiation, and the formation of specialized tissues and organs. Within this critical period, two fundamental processes, cleavage and gastrulation, stand as pivotal milestones. These stages are not merely sequential events but are profoundly interconnected, with the outcomes and cellular arrangements established during cleavage directly influencing the possibilities and patterns of the subsequent gastrulation. Together, they orchestrate the profound transition from a singular cell into an organized, multicellular structure capable of developing into a fully formed organism.

II. Cleavage: The Foundation of Multicellularity

Cleavage is defined as a rapid succession of mitotic cell divisions that commence immediately after fertilization of the zygote (Gilbert, 2000). A defining characteristic of this process is the division of the substantial volume of the egg cytoplasm into numerous smaller, nucleated cells, known as blastomeres, without any increase in the embryo's overall cytoplasmic volume (Gilbert, 2000).

The primary objective of cleavage is to dramatically amplify the cell number within the developing embryo and to establish a precise nuclear-to-cytoplasmic ratio within each nascent cell (Gilbert, 2000). This rapid proliferation is essential, as it prepares the embryo with a sufficient cellular mass for the intricate cell movements and subsequent differentiation that will define gastrulation and the later stages of organogenesis. By systematically partitioning the original egg cytoplasm, cleavage effectively "cellularizes" the embryo, creating discrete cellular units that are poised to undertake specialized roles in the developing structure.

Early Cleavage Stages from Zygote to Blastocyst

 

Key Characteristics of Cleavage

Cleavage exhibits several distinctive characteristics that set it apart from typical somatic cell division:

• Rapid Cell Division: Cleavage involves exceptionally fast mitotic cycles, often significantly more rapid than those observed in typical somatic cells (Gilbert, 2000). This accelerated pace is achieved by largely abbreviating or eliminating the G1 and G2 phases of the cell cycle, thereby focusing primarily on DNA synthesis (S phase) and mitosis (M phase) (Gilbert, 2000). For instance, a frog egg can undergo divisions to produce 37,000 cells in a mere 43 hours (Gilbert, 2000). Even more strikingly, Drosophila embryos demonstrate divisions occurring every 10 minutes for over 2 hours, culminating in approximately 50,000 cells within 12 hours (Gilbert, 2000).
• No Overall Embryo Growth: In stark contrast to typical cell proliferation, cleavage does not result in an increase in the total size or volume of the embryo (Gilbert, 2000). Instead, the egg's original cytoplasm is simply subdivided into progressively smaller blastomeres (Gilbert, 2000). This conservation of overall volume is a critical adaptation, as the early embryo frequently relies on stored maternal resources, such as yolk, within the original egg for its initial development and energy needs.
• Maternal Control: In many species, the initial stages of cleavage are predominantly regulated by proteins and messenger RNAs (mRNAs) that were pre-synthesized and stored within the oocyte by the mother (Gilbert, 2000). During this early phase, the zygote's own genome remains largely quiescent, with minimal or no transcription occurring (Gilbert, 2000). This reliance on maternal programming ensures a rapid and consistent initiation of development, providing a robust foundation before the embryonic genome becomes fully active.
• Mid-Blastula Transition (MBT): As cleavage progresses and the ratio of nuclear volume to cytoplasmic volume reaches a crucial threshold, a significant developmental event known as the mid-blastula transition (MBT) takes place (Gilbert, 2000). At this juncture, the rate of cell division typically decelerates, blastomeres acquire motility, and, most importantly, the embryo's own nuclear genes begin to be actively transcribed—a process termed zygotic gene activation (Gilbert, 2000). This marks a fundamental shift in developmental control, transitioning from a state primarily governed by maternal factors to one where the embryo's own genetic program takes the lead. For example, in the African clawed frog (Xenopus laevis), this transition typically occurs after approximately 12 cell divisions (Gilbert, 2000). This transition represents a critical developmental checkpoint, where the embryo effectively "takes the reins" of its own development. The initial rapid cleavage, under maternal control, efficiently generates a sufficient cell number. The subsequent decrease in the cytoplasmic-to-nuclear volume ratio then serves as a quantitative trigger, signaling the embryo's readiness for more intricate genetic regulation. This shift enables the initiation of species-specific developmental programs and complex cell fate decisions that would be too elaborate for maternal mRNA alone.
• Coordination of Karyokinesis and Cytokinesis: Cleavage necessitates the precise coordination of two fundamental cellular processes: karyokinesis, the mitotic division of the nucleus facilitated by the mitotic spindle and microtubules, and cytokinesis, the division of the cytoplasm by a contractile ring composed of actin microfilaments (Gilbert, 2000). The mitotic spindle and the contractile ring are positioned perpendicularly to each other, ensuring the accurate bisection of the cell and the production of two genetically equivalent daughter cells (Gilbert, 2000).
• Influence of Yolk: The quantity and distribution of yolk, which serves as the primary nutrient reserve within the egg cytoplasm, exert a profound influence on both the pattern and speed of cleavage (Bastiani, n.d.; Gilbert, 2000). Yolk, being a dense and metabolically inert substance, physically impedes the progression of the cleavage furrow, either slowing it down or preventing its complete penetration through the egg (Bastiani, n.d.; Gilbert, 2000). This direct physical constraint is a primary factor driving the remarkable diversity in cleavage patterns observed across the animal kingdom (Bastiani, n.d.; Gilbert, 2000). This highlights how nutrient availability, an environmental factor, directly shapes the fundamental developmental process of cell division. The resulting patterns of cell size and distribution, such as the smaller animal pole cells versus larger vegetal pole cells in amphibians, or the formation of a blastodisc in birds, directly influence the initial architecture of the embryo. This initial morphology, in turn, dictates the subsequent complex cell movements and germ layer formation during gastrulation, illustrating a clear cause-and-effect relationship from maternal provisioning to the embryo's early structural organization.

Blastomeres, Morula, Blastula, and Blastocyst

The process of cleavage gives rise to a series of distinct embryonic stages:

• Blastomeres: These are the individual cells produced by the mitotic divisions during cleavage (Gilbert, 2000; News-Medical, n.d.). They are typically smaller in size than the original zygote. Blastomeres serve as the fundamental cellular units of the early embryo, and their positions and developmental fates are progressively determined as the embryonic journey unfolds.
• Morula: The morula represents an early embryonic stage characterized by a solid ball of cells, typically comprising 16 to 32 blastomeres (News-Medical, n.d.). Its name, derived from the Latin morum meaning mulberry, reflects its resemblance to the fruit. The morula forms after approximately four initial cell divisions (News-Medical, n.d.).
• Blastula: The blastula is a later stage of cleavage, generally formed when the embryo consists of around 100 cells (Gilbert, 2000; News-Medical, n.d.). Structurally, the blastula is typically a hollow spherical layer of cells, termed the blastoderm, which encloses a fluid-filled central cavity known as the blastocoel or blastocele (Gilbert, 2000; News-Medical, n.d.). This blastula structure is the direct precursor that undergoes extensive and dramatic rearrangement during the process of gastrulation (Gilbert, 2000).
• Blastocyst (in Mammals): In most mammals, including humans, the blastula undergoes further differentiation to form a more complex structure called the blastocyst (News-Medical, n.d.). The blastocyst is uniquely characterized by the presence of two distinct cell populations: an outer layer of cells known as the trophoblast, and an internal cluster of cells referred to as the inner cell mass (ICM) (News-Medical, n.d.). The trophoblast layer will ultimately contribute to the formation of the placenta, which facilitates nutrient exchange with the mother, while the inner cell mass is fated to give rise to the embryo proper (Gilbert, 2000). This specialized blastocyst structure distinguishes mammalian early development from the simpler blastula found in many other animal groups (News-Medical, n.d.).

Types of Cleavage: Holoblastic vs. Meroblastic

The patterns of cleavage are fundamentally dictated by the quantity and distribution of yolk within the egg (Bastiani, n.d.; Gilbert, 2000). Yolk, being a dense and metabolically inert substance, physically impedes the progression of the cleavage furrow (Bastiani, n.d.; Gilbert, 2000). This physical constraint leads to two broad categories of cleavage: holoblastic (complete) and meroblastic (incomplete) (Bastiani, n.d.; Gilbert, 2000; Scribd, 2021).

• Holoblastic Cleavage (Complete) In holoblastic cleavage, the cleavage furrow extends entirely through the egg, completely dividing it into separate blastomeres (Bastiani, n.d.; Gilbert, 2000; Scribd, 2021). This type of cleavage is characteristic of zygotes containing relatively little yolk (isolecithal eggs) or a moderate amount of yolk (mesolecithal eggs) (Bastiani, n.d.; Gilbert, 2000).
• Radial Holoblastic Cleavage: In this pattern, the cleavage planes are typically oriented either parallel or perpendicular to the animal-vegetal axis of the egg. This results in the formation of tiers of cells that are directly aligned or stacked on top of each other, creating a distinct radial symmetry (Bastiani, n.d.; Scribd, 2021).
• Organisms: This pattern is observed in echinoderms, such as sea urchins, and in amphibians, including frogs (Bastiani, n.d.; Scribd, 2021).
• Specifics: In sea urchins, the first two cleavages are meridional, followed by an equatorial third cleavage. The fourth cleavage is unequal, producing eight equal-sized mesomeres at the animal pole and four large macromeres along with four much smaller micromeres at the vegetal pole (Bastiani, n.d.). In amphibians, the substantial volume of yolk (mesolecithal) significantly slows down cleavage at the vegetal pole. This disparity in division rates leads to the formation of smaller micromeres at the animal pole and larger, yolk-filled macromeres at the vegetal pole (Bastiani, n.d.).
• Spiral Holoblastic Cleavage: Here, the cleavage planes are oblique to the animal-vegetal axis. Consequently, the cells of each new tier are positioned in the furrows between the cells of the underlying tier, resulting in a characteristic spiral arrangement of blastomeres (Bastiani, n.d.; Scribd, 2021).
• Organisms: This pattern is found in mollusks, annelids, and flatworms (Bastiani, n.d.; Scribd, 2021).
• Bilateral Holoblastic Cleavage: The defining feature of bilateral holoblastic cleavage is that the very first cleavage divides the zygote into two halves that are exact mirror images of each other. All subsequent cleavages then maintain this established bilateral symmetry (Bastiani, n.d.; Scribd, 2021).
• Organisms: This type of cleavage is observed in ascidians, also known as tunicates (Bastiani, n.d.; Scribd, 2021).
• Rotational Holoblastic Cleavage: This pattern is characterized by asynchronous cell divisions and unique cleavage planes. The initial cleavage is meridional. However, during the second cleavage division, one of the two blastomeres divides meridionally, while the other divides equatorially (Bastiani, n.d.). This pattern is also notably slow compared to other cleavage types.
• Organisms: Rotational holoblastic cleavage is characteristic of mammals (including humans) and nematodes (Bastiani, n.d.; Scribd, 2021). Notably, mammalian cleavage is also regulated by the zygotic nucleus from the very beginning, a distinction from many other species where maternal control predominates early on (Bastiani, n.d.).

Holoblastic Cleavage Patterns

• Meroblastic Cleavage (Incomplete) In meroblastic cleavage, the cleavage furrow does not extend through the entire egg; instead, only a portion of the cytoplasm undergoes division (Bastiani, n.d.; Gilbert, 2000). This incomplete division occurs in zygotes that possess large, dense accumulations of yolk, characteristic of telolecithal (yolk concentrated at one end) or centrolecithal (yolk concentrated in the center) eggs (Bastiani, n.d.; Gilbert, 2000).
• Discoidal Meroblastic Cleavage: Cleavage in this pattern is confined to a small, yolk-free disc of cytoplasm, often referred to as the blastodisc, which is situated at the animal pole of the egg (Bastiani, n.d.; Scribd, 2021). The dense yolk mass prevents the cleavage furrows from penetrating completely, meaning the blastomeres remain continuous with the underlying yolk at their vegetal margins (Bastiani, n.d.; Scribd, 2021).
• Organisms: This type of cleavage is observed in fish, birds (e.g., chickens), and reptiles (Bastiani, n.d.; Scribd, 2021).
• Superficial Meroblastic Cleavage: This pattern occurs in eggs characterized by a large central yolk mass (centrolecithal eggs). The cleavages are restricted to the cytoplasmic rim, or periphery, of the egg (Bastiani, n.d.; Gilbert, 2000). Initially, nuclei divide repeatedly without accompanying cytokinesis, resulting in a multinucleated cytoplasm known as a syncytium (Bastiani, n.d.; Gilbert, 2000). These "naked" nuclei, termed energids, then migrate to the periphery, forming a syncytial blastoderm (Bastiani, n.d.; Gilbert, 2000). Subsequently, cell membranes form around each individual nucleus, leading to the creation of a cellular blastoderm (Bastiani, n.d.; Gilbert, 2000).
• Organisms: Superficial meroblastic cleavage is characteristic of most insects, with Drosophila serving as a classic example (Bastiani, n.d.; Gilbert, 2000; Scribd, 2021).

Meroblastic Cleavage Patterns

The table below provides a concise summary of the diverse cleavage types and their characteristics:

Cleavage Type	Sub-type	Description of Cleavage Pattern	Yolk Amount/Distribution	Representative Organisms
Holoblastic (Complete)	Radial	Furrows parallel/perpendicular to animal-vegetal axis; tiers of cells stacked. Unequal in amphibians due to yolk.	Isolecithal (little yolk), Mesolecithal (moderate yolk)	Echinoderms (Sea Urchins), Amphibians (Frogs) (Bastiani, n.d.; Scribd, 2021)
	Spiral	Furrows oblique to animal-vegetal axis; cells in furrows of underlying tier, spiral arrangement.	Isolecithal	Mollusks, Annelids, Flatworms (Bastiani, n.d.; Scribd, 2021)
	Bilateral	First cleavage divides into mirror halves; subsequent divisions maintain bilateral symmetry.	Isolecithal	Ascidians (Tunicates) (Bastiani, n.d.; Scribd, 2021)
	Rotational	Asynchronous divisions; one blastomere divides meridionally, other equatorially in 2nd cleavage. Slow.	Isolecithal	Mammals, Nematodes (Bastiani, n.d.; Scribd, 2021)
Meroblastic (Incomplete)	Discoidal	Cleavage restricted to a small blastodisc at animal pole; furrows don't penetrate dense yolk.	Telolecithal (dense yolk at one end)	Fish, Birds (Chicken), Reptiles (Bastiani, n.d.; Scribd, 2021)
	Superficial	Nuclei divide in central yolk, then migrate to periphery; no initial cytokinesis, forms syncytium.	Centrolecithal (yolk in center)	Most Insects (Drosophila) (Bastiani, n.d.; Gilbert, 2000; Scribd, 2021)

 

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References

Bastiani, M. J. (n.d.). Developmental Biology: Cleavage. University of Utah.(https://bastiani.biology.utah.edu/courses/3230/DB%20Lecture/Lectures/a6Cleav.html)

Bayquen, C. L. B. (n.d.). Gastrulation. Scribd. https://www.scribd.com/document/381130893/Gastrulation

CK-12 Foundation. (n.d.). What is the gastrulation process? CK-12. https://www.ck12.org/flexi/biology/embryo-growth/what-is-the-gastrulation-process/

Fiveable. (n.d.). Gastrulation: Formation of germ layers.(https://library.fiveable.me/developmental-biology/unit-3/gastrulation-formation-germ-layers/study-guide/SSdB9xdwABOa8oxE)

Fiveable. (n.d.). Germ layer derivatives. https://library.fiveable.me/lists/germ-layer-derivatives

Gilbert, S. F. (2000). Developmental biology (6th ed.). NCBI Bookshelf.(https://www.ncbi.nlm.nih.gov/books/NBK9992/)

Gilbert, S. F. (2000). Early Drosophila development. In Developmental biology (6th ed., Chapter 9). NCBI Bookshelf.(https://www.ncbi.nlm.nih.gov/books/NBK10081/)

Gilbert, S. F. (2000). Early mammalian development. In Developmental biology (6th ed., Chapter 11). NCBI Bookshelf.(https://www.ncbi.nlm.nih.gov/books/NBK10052/)

Ichikawa, T., Hanafusa, H., Kishi, K., & Saga, Y. (2013). Live imaging of whole mouse embryos during gastrulation: Migration of epiblast and mesodermal cells. PLoS One, 8(5), e64506. https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0064506

Ichikawa, T., Hanafusa, H., Kishi, K., & Saga, Y. (2014). Live imaging and quantitative analysis of gastrulation in mouse embryos using light-sheet microscopy and 3D tracking tools. Nature Protocols, 9(12), 2788–2801. https://www.janelia.org/sites/default/files/Labs/Keller%20Lab/Ichikawa%202014.pdf

News-Medical. (n.d.). Formation of blastula.(https://www.news-medical.net/health/Formation-of-Blastula.aspx)

OpenStax. (n.d.). 13.2 Development and Organogenesis. BCcampus Open Education. https://opentextbc.ca/biology/chapter/13-2-development-and-organogenesis/#:~:text=Cells%20in%20each%20germ%20layer,gut%20and%20many%20internal%20organs.

Riesgo, A., & Wessel, G. M. (2021). Gastrulation in the sea urchin embryo: An extraordinarily simple and elegant process. Developmental Dynamics, 250(3), 302–316. https://pmc.ncbi.nlm.nih.gov/articles/PMC7941261/

Scribd. (2021). 5-Cleavage. https://www.scribd.com/document/532324503/5-Cleavage

Slideshare. (n.d.). Gastrulation in frog. https://www.slideshare.net/slideshow/gastrulation-in-frog/235524436

SS CASC. (n.d.). Zoology II Sem Zoology.(https://www.sscasc.in/wp-content/uploads/downloads/Zoology/II-Sem-Zoology-.pdf)

Synopsis IAS. (2024, December 5). Illustrate the process of development during gastrulation in a chick embryo. https://synopsisias.com/blog/illustrate-the-process-of-development-during-gastrulation-in-a-chick-embryo-ias-201915-marks?category_slug=zoology-optional-paper-2-2019-with-solutions

Wikipedia contributors. (n.d.). Ingression (biology). Wikipedia. https://en.wikipedia.org/wiki/Ingression_(biology

Yang, X., Dormann, D., & Brand, M. (2002). Cell movement patterns during gastrulation in the chick are controlled by positive and negative chemotaxis mediated by FGF4 and FGF8. Developmental Cell, 3(3), 425–437. https://pubmed.ncbi.nlm.nih.gov/12361604/