EP_Somite development_2020_2021 SR FIN 2 PDF

Histology and embryology. Cytophysiology. Somite development dr n. med. Sylwia Rzeszotek 1st year Medicine 2020/2021 Chair and Department of Histology and Embryology Pomeranian Medical University in Szczecin Lecture plan: Part I 1. Primary germ layers....

Histology and embryology. Cytophysiology. Somite development dr n. med. Sylwia Rzeszotek 1st year Medicine 2020/2021 Chair and Department of Histology and Embryology Pomeranian Medical University in Szczecin Lecture plan: Part I 1. Primary germ layers. 2. Formation of somitomers. 3. Formation of somites: - Wave gradient and oscillation clock - Ephrin B - Epithelial-mesenchymal conversion Part II 4. Differentiation of somites - The Sclerotome - Dermatome - Myotome Part I. Formation of somitomers and somites FERTILIZATION, CLEAVAGE AND WHAT'S NEXT... I AM ALREADY AFTER FERTILIZATION, CLEAVAGE AND GASTRULATION LOOK, DRAMA, WE CAN'T LOOK LIKE THIS MASSACRE, ECTODERM WE HAVE TO CHANGE SOMETHING MEZODERM WE ARE ENDODERM STARTING METAMORPHOSIS I DO NOT WANT TO BE ONLY THREE LAYERS BAG I AM ALREADY AFTER FERTILIZATION, CLEAVAGE AND GASTRULATION notochord ectoderm endoderm mezoderm gastrula longitudinal section of the gastrula cross sections of the gastrula http://mm.pwn.pl/ency  Why is SOMITOGENESIS important? The segmental body plan is fundamental to all vertebrate species. Segmentation is initiated by the somitogenesis process and provides the body with stiffness and flexibility. Somites in the future will diversify and initiate the development of the spine, skin and muscles. VERY IMPORTANT!!! Mesenchyme is sometimes called 4th germ layer. It is a very unique tissue. different muscles SOMITOGENESIS is a nice name for the somite formation process Somiteformation process This is the segmentation process of the paraxial mesoderm. It leads to the creation of SOMITOMERS and SOMITES. It takes place after initiated neurulation. Amniotic Notochord cavity Paraxial Intermediate mesoderm mesoderm Ectoderm Mesoderm https://beyondthedish.wordpress.com/tag/mesoderm/  SOMITOGENESIS - differentiation of intra-embryonic mesoderm, and more precisely, of the paraxial mesoderm During mesoderm differentiation, the mesenchymal tissue of the intra-embryonic mesoderm begins to form clusters in three regions and changes its name: Paraxial mesoderm (from the pharynx to the steak membrane) Intermediate mesoderm Lateral mesoderm (later divides into somatic and splanchnic mesoderm)  SOMITOGENESIS - segmentation of the paraxial mesoderm SOMITOMERS from the front The segmentation of the paraxial mesoderm begins at the beginning of the 3rd week of fetal life and will result in formation of clusters of mesenchymal (later epithelial-like) structures called somitomers and somites. Somitomer (less commonly: somatomer) - is a segment (fragment of the longer part) of a three- week-old embryo formed from loose tissue of the paraxial mesoderm. Somitomer consists of mesodermal cells, arranged in concentric coils around their own center, located on both sides along the neural tube. Image source: The Kyoto Collection images are reproduced with the permission of Prof. Kohei Shiota and Prof. Shigehito Yamada, Anatomy and Developmental Biology, Kyoto University Graduate School of Medicine, Kyoto, Japan for educational purposes only and cannot be reproduced electronically or in writing without permission.  SOMITOGENESIS - segmentation of the paraxial mesoderm SOMITOMERS from the front The segmentation of the paraxial mesoderm begins at the beginning of the 3rd week of fetal life. Segmentation produces clusters / groups of structures called somitomers and somites. SOMITOGENESIS - segmentation of the paraxial mesoderm SOMITOMERS from the front NEURAL TUBE SOMITE PARAXIAL MESODERM  SOMITOGENESIS - segmentation of the paraxial mesoderm SOMITOMERS from the front Around 19 days of prenatal life, a small region of the paraxial mesoderm in the cranial region begins to form a loose cluster. This takes place on both sides of the embryo midline - the first PAIR of somitomers was 7 formed. Somitomers are involved in the segmentation of the neural plaque, the production of neuromers and mesenchymes of the head, and skeletal muscles of the head. Vera R. Sperling, Embryology of the Neck. Embryology, Anatomy, Normal Findings, and Imaging Techniques. Radiology key.  SOMITOGENESIS - segmentation of the paraxial mesoderm SOMITOMERS from the front Almost immediately after the first PAIR of somitomers is formed, more PAIRS of somitomers are formed. They arise caudal to the first pair. We will be here later Somites develop sequentially Stepbystep The first 7 somitomers will form the jaws, face, and throat. They will not become somites, but will remain attached to the neuromers in the head. Neuromers are morphologically or molecularly defined transitional segments of an early developing neural tube.  The formation of somites The first SOMITE is formed in the occipital region around the 20th day of fetal life. Somites develop immediately after formation of the 7th somitomer caudal. Somites are much more strongly segmented than somitomeres and their tissue is more compact..  What is SOMITE? SOMITE - is a symmetrical highly segmented structure appearing in a specific period of prenatal development (time frame) located symmetrically lateral to the neural tube. Somite differentiation will lead to the following: - vertebrae - most of the muscles of the body wall and limbs - skin - the dura mater and its blood vessels - axial skeleton (including the auditory processes and hyoid bone). NEURAL TUBE SOMITE PARAXIAL MESODERM  Somites develop sequentially Further pairs of somites develop in the direction of the head (skull) towards the tail and created one after the other or sequentially. The place of their formation has a special name - it is a presomic mesoderm. Shigeru Kondo, Science 14 Feb 2014: Vol. 343, Issue 6172, pp. 736-737; DOI: 10.1126/science.1250245  Somites develop sequentially Approximate age No. Of [days] somites 20 1-4 21 4-7 22 7-10 23 10-13 24 13-17 25 17-20 26 20-23 27 - 23-26 28 26-29 Neural 30 34-35 Somitocele Somite Notochord tube Until the end of 35 42-44 The final number is the 38-somite pairs, as several terminal pairs (and possibly front) soon disappears. 38  Somites develop sequentially No. of pairs Localisation 7 Somitomers cranial 4 Somites occipital 8 Somites cervical ITemigrat 12 Somites thoracic 5 Somites lumbar 5 Somites sacral 8-10 Somites coccygeal 748 1255 2 - 10 - -  clock war Segmentation clock and wave front model ↓ i Pro a The relevant to time (stage of prenatal life) cyclic processes of differentiation somites are defined as dependent on the clock segmentation and wave front (clock and wavefront model). This means that the differentiation depends on the oscillatory (= cyclic) expression of certain genes in the paraxial mesoderm (segmentation clock), and the concentration of specific factors (wave front). Notch protein accumulates in the presomic (paraxial) mesoderm, from which the next somite will be formed, and then its concentration is lowered (after somite formation). The Notch protein activates other genes involved into segmentation. A A A A Somites Somites B B B B Notch Notch Paraxial Notch Notch mesoderm Notch pro  The segmentation of the presomic mesoderm depends from the segmentation clock and wave front RA RA A A A A Somites B RA B B B Paraxial RA Notch Notch RA C C mesoderm FGF/WNT Notch Notch FGF/WNT FGF/WNT FGF Fibroblastgrowth FGF factor The genes that are cyclically activated in the presomitarian mesoderm include Notch and WNT. -O FGF8 and the transcription factor WNT vs RA --> establish an opposing gradient in the cranio-caudal axis. They quench each other during expression regulating the segmentation clock and NOTCH pathway activity. FGF8 - F.- ~ Ack Lu HY Criteria for the entry of paraxial mesoderm into somitogenesis punsel wave front RAM and Wnt IGFh Within the mesoderm, the embryonic disc has a gradient of RA as well as FGF and Wnt. Only a region with a high concentration of RA and a low concentration of FGF and Wnt can initiate somitogenesis - this is the so-called wave front model. Of course, 2 factors are not enough   Activation of FGF expression and the Wnt transcription factor leads to the activation of the Notch signaling pathway. Notch is responsible for the activation of at least two important transcription factors in somite differentiation: - Lunatic Fringe gene lunatic Fringa - Transcription factor HES1 (c-hairy) tranHES1  Further Somite Activation and Segmentation. FGF Writ - Notch The many roles of Notch signaling during vertebrate somitogenesis Author: Kanu Wahi,Matthew S. Bochter,Susan E. Cole Publication: Seminars in Cell & Developmental Biology Publisher: Elsevier Date: January 2016  Somites cannot adhere to each other Somites cannot stick to each other. To avoid "sticking" together, somites secrete proteins - ephrins B. The pre-formed somite secretes ephrin B, which binds to a specific receptor on the somite that is almost complete. This ligand-receptor interaction prevents neighboring somites from sticking to each other. Ephrin B is additionally responsible for creating gaps between somitomers (intersomitic space). Cdc42 Ephrin B intersomitic space EphA4 = receptor for Ephrin B  Now just the mesenchymal-epithelial conversion and the SOMITE is created epiteldal liketo Stille together relase they The ectoderm derived Wnt penetrates into the nearly completed somite and turns off the Snail gene. High Wnt and low Snail = mesenchymal cells become epithelial like tissue = transformation  ready somite. The genes for the components of the extracellular matrix (fibronectin) and CAM (N-cadherin) are activated. During segmentation, there is a change / transition of the nature of the mesenchymal tissue of the paraxial mesoderm to the epithelial like tissue. -put Wif Somites develop sequentially  Somites specification– HOX code Somites and their sclerotomas are identical, but the vertebrae are different... The explanation is the so-called HOX code (HOX-code), i.e. a differentiated profile of HOX gene expression. The Hox code describes a series of rules regarding the expression of Hox genes (homeobox) and their effect on segment identity. Horabin, Jamila. (2013). Long noncoding RNAs as metazoan developmental regulators. Chromosome research : an international journal on the molecular, supramolecular and evolutionary aspects of chromosome biology. 21. 10.1007/s10577-013-9382-8. SOMITOGENESIS somitogenesi  Part II Differentiation of somites Dermatome Myotome Sclerotome  Differentiation of somites Each mature somite undergoes internal differentiation - it begins to divide into an anterior (head) and a posterior (caudal) part. Each of these parts is programmed with different gene expression profiles, crucial for the formation of vertebrae, axons and neural crests. After epithelial transformation, cells begin to arrange themselves into spherical structures, giving rise to what we will call the somitocele, and its cells - somitocele cells - these cells are surrounded by epithelial like cells. dritt i Bodo Christ · Ruijin Huang · Martin Scaal Formation and differentiation of the avian sclerotome ventral Anatomy and Embryology volume 208, pages333–350(2004  1 Differentiation of somite in different planes 4th week: The cells of the abdominal and medial somite walls no longer adhere tightly to each other, they become multi-shaped and arrange themselves around the dorsal chord. ectoderm epidermisfrom Dorsolateral cells Dermomyotome Dermatome Dermomyotome Lateral myotome + myotome dermis Lateral Notochord Notochord Sclerotome sclerotome Ventromedial Notochord Axial somite cells (these sclerotome are those from de- epithelialization) noepitdial discs  Differentiation of somites Somites are activated by transcription factors derived from the dorsal cord and neural tube: Noggin Sonic hedgehog The transcription factors Pax-1 and Pax-9 will be activated in the ventromedial part of somite epithelial like cells. Pax -  Differentiation of somites Pax-1 and Pax-9 are responsible for the epithelial-mesenchymal transformation (yes, now the transformation is going back this way) of the somite cells, but ONLY IN THE VENTRO-MEDIAL REGION! The so-called SECONDARY MESENCHYMAL TISSUE. We walked the path: Mesenchymal tissue (paraxial mesoderm)  epithelial like tissue (somite)  mesenchymal tissue (ventromedial somite region). Cade What does this mean for the ventromedial somite region? - decrease in CAM expression (switching off N-cadherin genes) - turn off genes responsible for the production of basement membrane proteins. The ventromedial parts of somites, which after transformation become SCLEROTOME cells, migrate around the developing neural tube and notochord during multiple mitotic divisions. They make up a structure called a sclerotome. Warning! - the remaining part of the somite (now called the Dermomyotome) is still epithelial like tissue at this stage.  Differentiation of somites Why embryo needs sclerotome? The sclerotome has ability to activate genes responsible for the production of the cartilage extracellular matrix (e.g. proteoglycans, chondroitin sulphate) -> vertebrae, ribs. Sclerotome gives rise to: Specification Sclerotome cel of sclerotome Sclerotome cells - bones migration Sclerotome cells cel precursors reside on primary - cartilage tissue (attracted by spread over dorsal in posterior dorsal aorta primary dorsal aorta - blood somite aorta) - adipose tissue - spleen Dorsal - smooth muscles root - endothelium. ganglion Definitive dorsal Primary Notch aorta dorsal aorta Ephrin  Differentiation of somites Each sclerotome divides into a cranial and a caudal part. The caudal part is more dense, while the cephalic tissue is looser. The head and caudal segments of adjacent sclerotomes will form a vertebra. The axons of the motor neurons originating from the neural tube can pass through a loosely woven head segment.  Resegmentation of somites to form sclerotomes and changes of sclerotomal primordia to mature vertebral parts Resegmented Vertebral column Somite During resegmentation, the sklerotome sclerotes are formed from the Dense caudal and head portions of two Dense zone adjacent somites (center of the zone sclerotome = intersomitary Loose cleft). Loose zone zone The axial sclerotome and the intersomitic lateral sclerotome are divided cleft into a loose and dense zone. Dense zone of lateral sclerotome = vertebral arch and peduncle attaching to the vertebral body. Vertebral body = axial sclerotomy (loose and dense zone). axial lateral sclerotome sclerotome  Differentiation of somites Dermatome Dermatome Sclerotome Myotome Syndetome Myotome Sclerotome Syndetome - the layer between the sclerotome and the dermomyotome. It differentiates into precursors of tendocytes - tendon cells  of the tendon. 0 true It is also a process under tight molecular regulation. ↓tendan  Differentiation of somites The dorsolateral part of the somite is stimulated by Wnt (coming from the ectoderm and neural tube). Has the ability to express, among others Pax-3 and Pax-7. We will call this part of the somite at this stage of development "dermomyotome". - The cells of the dermomyotome have the ability to migrate. They will soon differentiate to form dermatome and myotome. DERMOMYOTOME Wat Pax 3, PaNZ  Differentiation of somites Dermatome - structure located closer to the ectoderm. Dermatome progenitors + cells from the lateral mesoderm will initiate the formation of the dermis and subcutaneous tissue. WARNING! The epidermis is derived from the ectoderm !!! Myotome - the part closer to the neural tube. It will soon contribute to the development of the skeletal muscles of the body walls, limbs and back.  Differentiation of somites Dermatome - why was it created? The first thought is that dermatome is responsible for the production of the dermis. The central part of the dermatome also gives rise to: tissue brown adipose certain skeletal muscles brown adipose tissue. skielba musch  Differentiation of somites What is the benefit from the creation of myotome? Myotome = Muscle Segments Gr. Myo = Muscle + Tomes = Segments, Segments, Volume Myotome is a group of muscles innervated by one nerve. OR It is the part of the somite that will give rise to the muscles. Body segmentation has a practical aspect. By examining a specific movement / reaction, the appropriate part of the spinal cord / nerve can be examined  generalisation  Differentiation of somites The myotome is a segment of muscle, part of the somites that is the future skeletal muscle. Each myotome is connected to a specific neuromer (neurotome - segment of the spinal cord) and a dermatome (skin segment). trapulies not Mike t Quest Myotome: Dorsal - back muscles (excluding the trapezius and broad back), extensor muscle of the limbs. Ventrolateral - the muscles of the ventrolateral surface of the body. Abdominal flat muscles (expiratory), rectus abdominis, limb flexor.  Differentiation of somites Myotome: Dorsomedial region Dermatome - Ventro-lateral region - abdominal wall - rectus abdominis muscle, internal and external oblique muscle, the transverse Ventrolateral abdominal muscles and the muscles of the region limbs). - Dorsomedial region (back muscle, the muscle of the shoulder blade, intercostal muscle). Human embryo in the 6th week of pregnancy. HE. Myotomes (M) with spindle-shaped myoblasts with slightly eosinophilic cytoplasm (arrows). Mage × 200.  Differentiation of somites The mesenchyme in the region of the myotome gives rise to MYOBLASTS that form the muscles of the trunk. Myoblasts are precursors of muscle cells. Limb muscles develop from myogenic precursor cells (and these come from the ventral region of the dermomyotome) in response to molecular signals. Myogenic precursors begin to migrate to the limb buds, then undergo epithelial-mesnenchymal transformation. Myogenesis is the process of muscle formation - the mark of its onset is the elongation of the nuclei and bodies of mesenchymal cells that differentiate into myoblasts. These myoblasts will soon fuse to form myotubes, myofilamets and also to form myofibrils. W  Differentiation of somites Preotic myotomes Occipital Trunk muscles (dorsal part) myotomes Upper limb extensor Cervical myotomes Trunk muscles (abdominal part) Eye Thoracic Upper limb flexor myotomes Intercostal Regressing muscles caudal Lumbar Heart myotomes myotomes Cross-section - division of the myotome into the dorsal and ventral parts. 6 week old embryo. The regions of the myotome that give rise to most skeletal muscles. Figury: Before we are born/9th edition. Moore, Persaud, Torchia  Differentiation of somites Eye muscles Facial muscles External oblique muscle Rectus abdominis muscle An 8-week old embryo. Developing muscles of the limbs and trunk.