Embryology Neurulation

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Post Graduate Academic presentation on neurulation

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Department of Clinical Anatomy:

Department of Clinical Anatomy Resident Presentation March 6 th , 2015

Neurulation:

Neurulation Dr. Bidur Adhikari Resident, MS Clinical Anatomy Dept. of Clinical Anatomy Maharajgunj Medical Campus

Objectives::

Objectives: General objectives: To discuss the process of neurulation in a human embryo. Specific objectives: Review of notochord formation Discussion of formation of neural plate Discussion of formation of neural tube, neuropores and their closure Discussion of fate of neural tube Mechanism involved in neurulation Clinical correlates

Introduction:

Introduction Neurulation is the process of formation of neural tube from neural plate Neural tube forms brain, spinal cord and other structures later on.

Review of notochord formation:

Review of notochord formation Formation of notochordal process which progresses to form notochordal plate and finally notochord

Events occurring in neurulation:

Events occurring in neurulation Four main events: formation of the neural plate, shaping of the neural plate, bending of the neural plate forming neural groove, closure of the neural groove to form neural tube and closure of neural tube at neuropores

Slide7:

Primitive node and primitive streak are visible in 18 day embryo A thickened area called neural plate forms in the ectoderm just cranial to the primitive node

Slide9:

In the neural plate, ectodermal cells differentiate into a thick plate of pseudostratified , columnar neuroepithelial cells which is now called the neuroectoderm . Neural plate forms first at the cranial end of the embryo and then differentiates in a cranial-to-caudal direction.

Slide11:

Scanning electron microscopy of a transverse section of developing embryo showing neural plate (NP), notochord (N) and surface ectoderm (SE)

Slide12:

By the end of the third week, the lateral edges of the neural plate become elevated to form neural folds (NF) , and the depressed mid region forms the neural groove (NG). Ventral most portion of neural tube is called median hinge point (MHP)

Slide14:

The neural plate folds during the 4th week to form a neural tube, the precursor of the central nervous system For the formation of a tube, the neural folds fuse with each other starting at the cervical region, 5 th somite. This continues cranially and caudally.

Slide16:

Surface ectoderm (SE), Neural tube (NT), notochord (N)

Slide17:

As fusion proceeds, two openings remain in neural tube: Anterior (cranial) neuropore Posterior (caudal) neuropore Three regions visible in the forming brain which later form Forebrain Midbrain Hindbrain

Slide19:

Cranial neuropore closes at 25 th day and caudal neuropores closes at 28 th day Closure of neuropore and formation of spinal cord and brain vesicles marks the completion of neurulation.

Slide21:

Neural tube attains C shape along with folding of the body

Secondary neurulation:

Secondary neurulation Formation of caudal neural tube from tail bud is called secondary neurulation. Central tail bud cells condense into a solid medullary cord which undergoes cavitation and merges cranially with neural canal of the neural tube. Secondary neurulation is completed by about 8 weeks of development

Slide25:

During folding and fusion, the lateral lips of the neural plate also give rise to an extremely important population of cells, neural crest cells , which detach during formation of the neural tube and migrate in the embryo to form a variety of structures

Fate of neural tube:

Fate of neural tube Prosencephalon : Telencephalon and diencephalon  cerebral hemispheres and basal nuclei Mesencephalon : Cerebral peduncles, tectum, tegmentum Rhombencephalon : Metencephalon and myelencephalon  cerebellum, pons, medulla oblongata Spinal cord All cranial and spinal motor nerves Astrocytes, oligodendrogliocytes , ependyma Neurohypophysis Retina, optic nerve

Mechanisms involved in neurulation:

Mechanisms involved in neurulation Signals for dorso ventral patterning of neural tube are received from adjacent tissues Surface ectoderm dorsally Paraxial mesoderm laterally Notochord ventrally

Slide28:

Sonic hedgehog ( Shh ), secreted initially by the notochord, is the signal that induces the median hinge point and floor plate. Shh also acts as a morphogen, such that high concentrations induce ventral neurons, lower concentrations induce more intermediate neurons, and the lowest concentrations induce more dorsal neurons

Slide29:

Through the neural tube, there is a dorsal to ventral concentration gradient of BMP produced by the surface ectoderm BMP signaling is antagonized by antagonists like Noggin, Chordin , Nodal follistatin and Cerberus. Chordin is a BMP antagonist, produced by notochord. It has ventral to dorsal gradient through the neural tube BMP signaling is robust dorsally. A high level of BMP signaling dorsally results in the induction of neural crest cells and the roof plate of the neural tube In presence of BMP signaling, ectoderm forms surface ectoderm. In its absence, ectoderm forms neural plate.

Slide30:

BMP signaling absent BMP signaling present Ectoderm Surface ectoderm Neural plate

Slide31:

Factors affecting the mechanism of neurulation

Slide32:

F actors produced by the paraxial mesoderm are Fgfs , such as Fgf8 Least information available about their mechanism

Clinical aspects:

Clinical aspects Neural tube defects: defect in closure of neuropores Caudal neuropore defects ( Spina bifida) defective closure of caudal neuropore. Aperta : caudal neuropore opens to skin Occulta : open caudal neuropore doesn’t open to skin Cystica : Meningocele , Meningomyelocele Cranial neuropore defects: Anencephaly: cranial neuropore opens outside Encephalocele : open cranial neuropore doesn’t open to skin

Slide34:

Diagrammatic spina bifida occulta

Slide36:

Clinical picture of spina bifida

Slide37:

Clinical picture and radiograph of encephalocele

Slide38:

Clinical picture of anencephaly

Neurulation in a nutshell:

Neurulation in a nutshell

References:

References Gray’s Anatomy, 39 th edition. (Susan Standring ) Langman’s Medical Embryology, 12 th edition. (T.W. Sadler) Larsen’s Human Embryology, 4 th edition. (Gary C. Schoenwolf , Steven B. Bleyl , Philip R. Brauer , Philippa H. Francis-west) The Developing Human, Clinically Oriented Embryology. (Moore , Keith L)

Disclaimer:

Disclaimer Presentation prepared as per academic curriculum to discuss materials in recommended academic texts. Pictures and written material have been taken from purchased copies of the reference material with minimal to no modification

Thank you:

Thank you

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