THIRD WEEK OF DEVELOPMENT – NEURULATION AND DEVELOPMENT OF SOMITES
Definition of Neurulation
Neurulation is a critical developmental process in vertebrate embryos that involves the transformation of the neural plate into the neural tube, which ultimately gives rise to the central nervous system (CNS), including the brain and spinal cord. This process occurs during the early stages of embryonic development when the embryo is referred to as a neurula.
Process of Neurulation
The process begins with the notochord, a rod-like structure that serves as a signaling center, inducing the overlying ectoderm germ layer to thicken and flatten into what is known as the neural plate. The neural plate then undergoes a series of morphological changes, including folding inward to form a groove along its length. As this folding progresses, the edges of the neural plate rise and eventually come together to fuse, forming the neural tube.
There are two main types of neurulation: primary neurulation and secondary neurulation, which occur in different species and involve distinct mechanisms.
- Primary Neurulation: In this type, the neural plate folds inward until its edges meet and fuse. This process is characterized by changes in cell shape and movement, particularly apical constriction where cells become taller and more columnar. The medial hinge point (MHP) forms at the center of this folding process, allowing for further bending and closure of the neural tube.
- Secondary Neurulation: This occurs in some species where instead of folding from a flat sheet, a solid precursor tissue undergoes cavitation or hollowing out to form the neural tube. This method is less common than primary neurulation but is essential for certain vertebrates.
Induction Mechanisms
The concept of induction plays a crucial role in neurulation. Induction refers to how one group of cells influences another group to differentiate into specific cell types. The dorsal lip of the blastopore has been identified as an “organizer” region that can induce surrounding ectodermal cells to become neural tissue through various signaling pathways involving growth factors such as bone morphogenetic proteins (BMPs) and inhibitors like noggin.
In summary, neurulation is an essential phase in embryonic development that establishes the foundation for forming complex structures within the central nervous system through intricate cellular processes involving induction, shape change, and folding.
Steps of Development of Neural Tube
1. Formation of the Primitive Streak
At the end of the second week of embryonic development, a structure known as the primitive streak appears in the epiblast layer of the bilaminar disk. This groove is crucial as it marks the beginning of gastrulation, where cells start to migrate and differentiate.
2. Gastrulation and Germ Layer Formation
Cells within the epiblast migrate downward through the primitive streak, leading to the formation of three germ layers from the initial two:
- Endoderm (innermost layer)
- Mesoderm (middle layer)
- Ectoderm (outermost layer)
The nervous system originates from the ectoderm.
3. Appearance of the Notochord
In the third week of development, a structure called the notochord forms in the mesoderm. The notochord plays a vital role by secreting growth factors that stimulate changes in adjacent ectodermal cells.
4. Formation of Neuroectoderm
The overlying ectoderm differentiates into neuroectoderm due to signals from the notochord. This differentiation results in a thickened structure known as the neural plate.
5. Elevation of Neural Folds
The lateral edges of the neural plate rise to form neural folds. As these folds elevate, they begin to move toward each other at the midline.
6. Formation of Neural Groove
As neural folds approach one another, a U-shaped neural groove forms between them, establishing boundaries between left and right sides of the embryo.
7. Fusion of Neural Folds
The neural folds eventually meet and fuse together at the midline, transforming the neural groove into a closed neural tube. This fusion is critical for proper development and occurs around four weeks after conception in humans.
8. Migration of Neural Crest Cells
During fusion, some cells within the folds detach and migrate away to form a distinct population known as neural crest cells. These cells will give rise to various structures including peripheral neurons, glial cells, melanocytes, and craniofacial cartilage.
9. Closure of Neuropores
Initially, there are openings at both ends of the neural tube called neuropores which remain open for a short period after tube formation. These neuropores close during week four; improper closure can lead to serious defects such as spina bifida or anencephaly.
10. Differentiation into Central Nervous System Structures
Once closed, further differentiation occurs within different regions along what will become defined areas:
- The forebrain (prosencephalon)
- The midbrain (mesencephalon)
- The hindbrain (rhombencephalon)
- The spinal cord
Each region develops into specific parts of the central nervous system through subsequent cellular proliferation and specialization.
Derivatives of Neural Crest Cells
Neural crest cells are a unique population of cells that arise during embryonic development and have the ability to migrate and differentiate into a diverse range of cell types. The derivatives of neural crest cells can be categorized into several key groups:
1. Craniofacial Structures
Neural crest cells contribute significantly to the formation of craniofacial structures, including bones and cartilage in the face and skull. This includes the maxilla, mandible, zygomatic bones, and parts of the cranial vault. These structures are essential for facial morphology and function.
2. Melanocytes
Melanocytes are pigment-producing cells located in the skin’s epidermis, specifically in the stratum basale layer. They are responsible for producing melanin, which gives color to the skin, hair, and eyes. Failure of neural crest cells to migrate properly can lead to conditions such as albinism.
3. Peripheral Nervous System (PNS) Components
Neural crest cells give rise to various components of the peripheral nervous system, including sensory neurons found in dorsal root ganglia (DRG) and autonomic ganglia. These neurons play critical roles in transmitting sensory information from the body to the central nervous system (CNS) and regulating involuntary functions.
4. Schwann Cells
Schwann cells are glial cells that myelinate axons in the PNS. Each Schwann cell typically myelinates a single axon, which is crucial for efficient nerve signal transmission. Schwann cells also assist in nerve regeneration after injury.
5. Enteric Nervous System
Neural crest derivatives include enteric neurons that form part of the enteric nervous system (ENS), often referred to as “the second brain.” The ENS controls gastrointestinal motility and secretion independently but also communicates with the CNS.
6. Endocrine Cells
Neural crest cells contribute to endocrine tissues such as chromaffin cells found in the adrenal medulla. These cells secrete catecholamines like epinephrine and norepinephrine, which are vital for stress responses.
7. Cartilage Structures
Various cartilaginous structures within the larynx and trachea derive from neural crest cells. This includes important cartilages such as thyroid cartilage, cricoid cartilage, arytenoid cartilages, and C-shaped rings supporting the trachea.
8. Dentin-forming Odontoblasts
During tooth development (odontogenesis), neural crest-derived odontoblasts produce dentin, a calcified tissue that forms beneath enamel in teeth.
9. Aorticopulmonary Septum
In cardiac development, neural crest cells play a role in forming structures like the aorticopulmonary septum which separates outflow tracts from both ventricles into respective arteries (pulmonary artery and aorta). Abnormalities here can lead to congenital heart defects such as transposition of great vessels.
These derivatives illustrate how versatile neural crest cells are during embryonic development; they contribute not only to structural components but also functional systems within vertebrates.
Congenital Anomalies Resulting from Abnormal Neurulation
Neurulation is a critical process in embryonic development that leads to the formation of the neural tube, which eventually develops into the central nervous system (CNS), including the brain and spinal cord. Abnormalities in this process can lead to various congenital anomalies, primarily affecting the CNS. Below are some of the key congenital anomalies resulting from abnormal neurulation:
1. Spina Bifida
Spina bifida is one of the most common neural tube defects (NTDs) and occurs when the neural tube does not close completely during early embryonic development. This condition can manifest in several forms:
- Spina Bifida Occulta: The mildest form, where there is a small defect in the bony encasement of the spinal cord, but no protrusion of spinal elements.
- Meningocele: In this type, the protective membranes (meninges) protrude through the defect in the vertebrae but do not include spinal nerves.
- Myelomeningocele: The most severe form, where both meninges and spinal nerves protrude through the defect, often leading to significant neurological impairment.
The exact cause of spina bifida is multifactorial, involving genetic predispositions and environmental factors such as folate deficiency during pregnancy.
2. Anencephaly
Anencephaly is a severe NTD characterized by incomplete development of the brain and skull. It results from failure of closure at the cranial end of the neural tube. Infants born with anencephaly typically lack major portions of their brain, particularly the cerebrum and cerebellum, leading to a very short life expectancy. This condition is also associated with maternal factors such as diabetes and obesity.
3. Encephalocele
Encephalocele occurs when there is a defect in the skull that allows brain tissue to protrude through an opening. This anomaly can vary significantly in size and location on the skull. Depending on how much brain tissue is involved and its location, encephaloceles can lead to varying degrees of neurological impairment.
4. Holoprosencephaly
Holoprosencephaly arises from incomplete cleavage of the forebrain during early embryonic development, leading to a single-lobed brain structure instead of two hemispheres. This condition can result in facial deformities such as cyclopia or cleft lip/palate and can range from mild to severe forms depending on how much separation occurs between hemispheres.
5. Chiari Malformation
Chiari malformation involves structural defects in the cerebellum that occur when part of it extends into the spinal canal due to improper closure of neural structures during neurulation. Symptoms may include headaches, neck pain, balance problems, and other neurological issues depending on severity.
6. Neural Tube Defects (NTDs)
In addition to spina bifida and anencephaly, other NTDs include conditions like encephaloceles or myeloschisis (where neural tissue remains open). These defects arise due to disruptions during neurulation caused by genetic factors or teratogenic influences such as certain medications or environmental toxins.
Conclusion
Abnormal neurulation leads to significant congenital anomalies primarily affecting CNS development. These conditions underscore the importance of proper maternal health care before and during pregnancy, including adequate intake of folic acid which has been shown to reduce risks associated with NTDs.
Formation of Three Germ Layers
The formation of the three germ layers—ectoderm, mesoderm, and endoderm—occurs during a critical phase of embryonic development known as gastrulation. This process is essential for the proper organization of cells in the developing embryo and ultimately leads to the formation of all tissues and organs.
1. Gastrulation Process
Gastrulation begins after the blastula stage, where the embryo consists of a hollow ball of cells. During this phase, the cells undergo significant rearrangement and differentiation. The first step involves the inward folding of a portion of the blastula, which creates an indentation called the blastopore. This indentation marks the beginning of germ layer formation.
2. Formation of Ectoderm and Endoderm
As gastrulation progresses, two primary germ layers are established: ectoderm and endoderm. The ectoderm forms from the outer layer of cells that remain on the surface after some cells migrate inward. This layer will eventually give rise to structures such as skin, hair, nails, and parts of the nervous system.
The endoderm is formed from cells that move inward through the blastopore to create an inner layer. This layer will develop into internal structures such as the lining of the gastrointestinal tract, lungs, liver, pancreas, and other associated glands.
3. Induction of Mesoderm
After ectoderm and endoderm have been established, interactions between these two layers induce the formation of a third layer known as mesoderm. The mesoderm arises from cells that migrate between the ectoderm and endoderm during gastrulation. This middle layer is crucial for forming various tissues including muscle, bone, connective tissue, heart, kidneys, and reproductive organs.
4. Differentiation into Specific Tissues
Once these three germ layers are formed—ectoderm (outer), mesoderm (middle), and endoderm (inner)—they begin to differentiate into specific cell types that will contribute to various organs in the body:
- Ectoderm: Develops into skin epidermis, hair follicles, mammary glands, and components of both central and peripheral nervous systems.
- Mesoderm: Gives rise to dermis (the inner skin layer), muscles (skeletal and smooth), bones (including bone marrow), heart tissue, kidneys, gonads (ovaries/testes), and blood vessels.
- Endoderm: Forms linings for internal organs such as intestines (small/large), stomach lining, lungs’ alveoli (air sacs), liver tissue, pancreas tissue among others.
In summary, through gastrulation’s complex cellular movements and interactions among these layers during early embryonic development, all three germ layers are established which serve as precursors for all organ systems in higher organisms.
Mesoderm Components: Paraxial, Intermediate, and Lateral Plate Mesoderm
The mesoderm is one of the three primary germ layers in the early embryo, which also includes the ectoderm and endoderm. It plays a crucial role in the development of various structures and systems within an organism. The mesoderm can be further divided into three distinct components: paraxial mesoderm, intermediate mesoderm, and lateral plate mesoderm. Each of these components has unique characteristics and developmental pathways.
1. Paraxial Mesoderm
The paraxial mesoderm is located adjacent to the notochord and neural tube during embryonic development. It is primarily responsible for forming somites, which are segmented blocks of tissue that give rise to important structures in the body.
- Somite Formation: The paraxial mesoderm differentiates into somites around the third week of human embryonic development. Each somite will eventually develop into vertebrae, skeletal muscles, dermis of the skin, and connective tissues.
- Skeletal Muscle Development: Myogenic progenitor cells derived from paraxial mesoderm contribute to the formation of skeletal muscle fibers through a process called myogenesis.
- Dermatome Formation: The dermatome portion of each somite contributes to the dermis layer of skin, providing structural support and housing various skin appendages.
In summary, paraxial mesoderm is crucial for axial skeleton formation, muscle development, and dermal structures.
2. Intermediate Mesoderm
The intermediate mesoderm lies between the paraxial mesoderm and lateral plate mesoderm. It plays a significant role in forming structures associated with the urogenital system.
- Kidney Development: The intermediate mesoderm gives rise to nephric structures such as pronephros (early kidney), mesonephros (transitional kidney), and metanephros (permanent kidney). This progression occurs during different stages of embryonic development.
- Gonadal Formation: Cells from the intermediate mesoderm also contribute to gonadal development (testes or ovaries) through processes involving sex differentiation influenced by genetic factors such as SRY gene expression.
- Urogenital Ducts: The intermediate mesoderm forms parts of urogenital ducts like Wolffian ducts (mesonephric) which are involved in male reproductive tract formation.
In essence, intermediate mesoderm is vital for developing kidneys and reproductive organs.
3. Lateral Plate Mesoderm
The lateral plate mesoderm is situated laterally in relation to both paraxial and intermediate mesoderms. It divides into two layers: somatic (parietal) layer and splanchnic (visceral) layer.
- Somatic Layer Contributions: The somatic layer contributes to the formation of body wall structures including bones, connective tissues, and serous membranes lining body cavities such as pleurae around lungs or peritoneum around abdominal organs.
- Splanchnic Layer Contributions: The splanchnic layer gives rise to components associated with internal organs including heart muscle (myocardium), blood vessels (vasculature), smooth muscle layers in digestive tract organs, and other visceral structures.
- Coelom Formation: The lateral plate mesoderm also plays a critical role in forming the coelom—an essential body cavity that separates internal organs from the body wall.
In summary, lateral plate mesoderm is integral for developing circulatory systems, body cavities, and visceral organ structures.
In conclusion, while all three components arise from the same germ layer—the mesoderm—they each have distinct roles in embryonic development leading to various organ systems within an organism.
Definition of Somites
Somites are a set of bilaterally paired blocks of paraxial mesoderm that form during the embryonic stage of somitogenesis in segmented animals. They are located on either side of the neural tube and play a crucial role in the development of various structures in vertebrates. Each somite subdivides into specific regions that give rise to important components of the body, including:
- Dermatomes: These contribute to the formation of skin and connective tissues.
- Myotomes: These develop into skeletal muscles.
- Sclerotomes: These are precursors for vertebrae and cartilage.
- Syndetomes: These give rise to tendons.
The process of somite formation is tightly regulated by genetic mechanisms, including signaling pathways such as Notch, Wnt, and fibroblast growth factor (FGF), which coordinate the timing and organization of somite development along the head-to-tail axis of the embryo. Somites also influence the migratory paths of neural crest cells and spinal nerves.
In summary, somites are essential embryonic structures that contribute significantly to the vertebrate body plan by differentiating into various tissues and organs.
Development of Somites and Their Relation to the Formation of Axial Skeleton and Associated Structures
Somites are segmented blocks of mesoderm that form along the developing neural tube in vertebrate embryos. They arise from the paraxial mesoderm during the process of somitogenesis, which begins around the third week of human embryonic development. Each somite is responsible for giving rise to various structures, including skeletal muscle, cartilage, tendons, and dermis.
Formation of Somites
The formation of somites occurs through a process called segmentation. This process is regulated by several signaling pathways, including the Notch, Wnt, and Fibroblast Growth Factor (FGF) pathways. The segmentation clock is a molecular mechanism that controls the timing and patterning of somite formation. As mesodermal cells undergo epithelial-to-mesenchymal transition (EMT), they become organized into somites.
Somitogenesis typically results in the formation of 42-44 pairs of somites in humans, which will eventually differentiate into specific structures along the body axis.
Role of Somites in Axial Skeleton Development
Somites play a crucial role in the development of the axial skeleton, which includes the vertebrae and associated structures such as ribs and intervertebral discs. Each somite differentiates into two primary components:
- Dermatomiotome: This part gives rise to dermis (skin) and skeletal muscles.
- Sclerotome: This part contributes to the formation of vertebrae and rib cartilages.
The sclerotome cells migrate medially around the notochord and neural tube to form vertebral bodies. The notochord itself plays an essential role as it provides signals necessary for proper sclerotome differentiation.
Mechanisms Involved in Sclerotome Formation
During sclerotome development, several key processes occur:
- Cell Migration: Cells from each sclerotome migrate towards the midline where they aggregate around the notochord.
- Differentiation Signals: Various growth factors such as Sonic Hedgehog (Shh) secreted by notochord influence sclerotome cell fate.
- Formation of Vertebral Structures: As these cells aggregate, they undergo further differentiation into chondrocytes that will form cartilage templates for future vertebrae.
The axial skeleton’s structure is established through a series of morphogenetic processes involving condensation (aggregation) followed by endochondral ossification where cartilage is replaced by bone.
Associated Structures Derived from Somites
In addition to forming vertebrae, somites contribute to other important structures:
- Ribs: The costal processes from thoracic sclerotomes develop into ribs.
- Intervertebral Discs: The remaining mesenchyme between adjacent sclerotomes forms intervertebral discs.
- Muscles and Dermis: The dermatomiotome gives rise to muscles associated with each segmental region as well as skin derivatives.
These associations highlight how somite-derived tissues are integral to both structural support (axial skeleton) and functional systems (musculature).
Conclusion
In summary, somites are fundamental units in embryonic development that contribute significantly to forming the axial skeleton and its associated structures through complex signaling pathways and cellular differentiation processes. Their proper development is crucial for establishing a functional musculoskeletal system in vertebrates.
Development of Intraembryonic Coelom and Primordial Cardiovascular System (CVS)
(a) Development of Intraembryonic Coelom
The intra-embryonic coelom is a crucial structure that forms during the early stages of embryonic development, specifically around the third week of gestation. It originates from the lateral plate mesoderm and plays a significant role in the formation of body cavities.
- Formation: The intra-embryonic coelom begins as a single cavity within the lateral plate mesoderm. This process occurs during week 3 of embryonic development, where the mesodermal layer differentiates into two parts: somatic (parietal) mesoderm and splanchnic (visceral) mesoderm. The coelomic cavity is established as these layers separate.
- Partitioning: As development progresses, this initial single cavity undergoes complex morphological changes, including folding and partitioning. By week 5, the coelom divides into three major body cavities:
- Pericardial Cavity: This cavity surrounds the heart.
- Pleural Cavities: These are two cavities that surround each lung.
- Peritoneal Cavity: This cavity houses abdominal organs.
- Serous Membrane Development: Each of these cavities is lined by a serous membrane, which consists of a squamous epithelium and underlying loose connective tissue. The serous membranes provide lubrication to allow organs to move smoothly against one another during development and later in life.
- Contribution to Organ Development: Portions of the walls of the intra-embryonic coelom contribute to various organs, including the adrenal glands, ovaries, and testes. The developing organs push against the walls of these cavities, leading to their eventual encapsulation by serosal/adventitial layers.
(b) Development of Primordial Cardiovascular System (CVS)
The primordial cardiovascular system begins forming concurrently with other structures during early embryogenesis and is essential for providing nutrients and oxygen to developing tissues.
- Early Formation: The cardiovascular system starts developing around week 3 with the formation of blood islands in the yolk sac and within the splanchnic mesoderm adjacent to the intra-embryonic coelom. These blood islands consist of hematopoietic stem cells that will eventually give rise to blood cells.
- Vascular Network Development: As these blood islands mature, they begin to fuse together to form a primitive vascular network. This network includes both arteries and veins that will supply blood throughout the embryo.
- Heart Formation: Concurrently, cardiac progenitor cells migrate towards the midline to form a linear heart tube by week 4. This heart tube undergoes looping and remodeling processes that lead to chamber formation (atria and ventricles) by week 5.
- Connection with Coelomic Cavities: The developing heart connects with vessels that emerge from it into various regions including those surrounding the pericardial cavity formed from the intra-embryonic coelom. This connection ensures efficient circulation as it develops further into a functional cardiovascular system capable of supporting fetal life.
- Integration with Other Systems: As development continues through weeks 6-8, further differentiation occurs within both systems (intra-embryonic coelom and CVS), ensuring proper integration between organ systems for effective function postnatally.
In summary, both the intra-embryonic coelom and primordial cardiovascular system develop intricately during early embryogenesis, laying down essential structures for future organ systems in vertebrates.
Development of Chorionic Villi
The development of chorionic villi is a critical aspect of placental formation and function during pregnancy. This process begins shortly after fertilization and continues through the early stages of embryonic development. Here’s a detailed step-by-step explanation of how chorionic villi further develop:
1. Initial Formation of Chorionic Villi: Chorionic villi originate from the trophoblast layer of the blastocyst, which differentiates into two main types: the syncytiotrophoblast (ST) and cytotrophoblast (CT). The CT cells invade the maternal endometrium, leading to the formation of primary villi around the 13th embryonic day (3 weeks 6 days gestation). These primary villi are finger-like projections that extend into the maternal tissue.
2. Development into Secondary Villi: As development progresses, mesodermal cells from the embryo invade these primary villi, transforming them into secondary villi. This invasion occurs around the 5th week of gestation. The mesodermal core provides structural support and will eventually give rise to blood vessels within the villi.
3. Formation of Tertiary Villi: By approximately 6 weeks of gestation, tertiary villi begin to form as fetal blood vessels develop within the mesodermal core. These vessels connect with the fetal circulatory system, establishing a functional vascular network that facilitates nutrient and gas exchange between maternal and fetal blood.
4. Maturation and Functional Adaptation: The chorionic villi continue to mature throughout pregnancy, adapting their structure to optimize their functions. The ST layer plays a crucial role in hormone production and immunological tolerance, while also facilitating nutrient transfer from maternal blood to fetal circulation. The surface area for exchange is increased by branching and proliferation of these villous structures.
5. Interaction with Maternal Blood Supply: As chorionic villi mature, they become surrounded by maternal blood pools known as intervillous spaces. The ST invades maternal spiral arteries, remodeling them to increase blood flow to the placenta while maintaining separation between maternal and fetal blood via a barrier formed by trophoblastic layers.
6. Role in Pregnancy Complications: Abnormalities in chorionic villus development can lead to complications such as fetal growth retardation (FGR) or hypertensive disorders during pregnancy (HDP). Understanding these processes is essential for developing interventions for perinatal diseases linked to placental insufficiency.
In summary, the further development of chorionic villi involves their initial formation from trophoblasts, transformation from primary to secondary and tertiary structures with vascularization, maturation for optimal function in nutrient exchange, interaction with maternal blood supply, and implications for pregnancy health.