Embryology: Skeletal And Muscular Systems

Front 1

Paraxial Mesoderm

Back 1

thick plate of mesoderm on each side of the midline organized in craiocaudal sequence into segments known as somitomeres

Front 2

Somititomeres 1-7 develop into?

Back 2

don't develop into somites, but contribute to mesoderm in head and neck, pharyngeal arches

Front 3

Somitomeres 8+ develop into?

Back 3

further condense into craniocaudal sequence to form 42-44 pairs of somites in trunk region, and have final count of ~35 pairs after caudal-most disappear

Front 4

Somites differentiate into?

Back 4

differentiate into:
--sclerotome: cartilage and bone component
--myotome: muscle component
--dermatome: dermis of skin

Front 5

Head and neck musculature derived from?

Back 5

somitomeres 1-7 of head and neck region, to form pharyngeal arches

Front 6

Extraocular muscles

Back 6

derived from somitomeres 1,2,3 &5; 1-3 are preotic myotomes/somites; innervated by CN III, IV and VI

Front 7

Tongue muscles

Back 7

derived from myotomes in occipital region & innervated by CN XII

Front 8

Trunk Musculature derived from and partition into?

Back 8

derived from myotomes in trunk region; partition into dorsal epimeres and ventral hypomeres

Front 9

Dorsal Epimeres

Back 9

develop into intrinsic back muscles & innervated by dorsal rami of spinal nerves

Front 10

Ventral Hypomeres

Back 10

develop into prevertebral intercostal and abdominal muscles; innervated by ventral rami of spinal nerves

Front 11

Limb musculature dervied from and differentiates into?

Back 11

myotomes/somites in upper limb bud and lower limb bud regions; mesoderm migrates to form posterior and anterior condensations

Front 12

Posterior Condensation

Back 12

1) devos into extensor & suppinator muscles of upper limb
2) devos into extensor and abductor muscles of lower limb

Front 13

Anterior Condensation

Back 13

1) devos into flexor and pronator muscles of upper limb
2) devos into flexor and adductor muscles of lower limb

Front 14

Smooth Muscles iof GI and Tunica Media of blood vessels

Back 14

derived from mesoderm

Front 15

Cardiac Muscle

Back 15

derived from mesoderm surrounding primitive heart tube & becomes myocardium

Front 16

Septum transversum devos from?

Back 16

Cerivcal somites (myotomes; innervated by phrenic nerve

Front 17

Abdominal muscles devos from?

Back 17

Hypomere (ventral part of myotome)

Front 18

Extrinsic eye muscles devos from?

Back 18

Preoctic somites (myotomes) found near prochordal plate; specifically, somitomeres 1-3

Front 19

tongue muscles devos from?

Back 19

Intrinsic and Extrinsic arise from occipital somites (myotomes)

Front 20

Erector spinae devos from?

Back 20

Epimere, from dorsal part of myotome

Front 21

Upper Limb devo begins with?

Back 21

activation of a group of mesodermal cells of the lateral plate of mesoderm

Front 22

Lateral plate mesoderm migrates into limb bud and?

Back 22

condenses along central axis, forming vasculature & skeltal components of upper limb

Front 23

Mesoderm from somites migrates to upper limb and?

Back 23

condenses to form musculature components of upper limb

Front 24

Hox 3.3?

Back 24

is expressed by future limb mesodermal cells prior to limb bud formation

Front 25

AER?

Back 25

Place at tip of limb bud where limb mesoderm is signaled to thicken; interacts with underlying mesoderm to promote outgrowth of limb bud by promoting mitosis & preventing terminal differntiation of mesodermal cells at tip of limb bud

Front 26

Zone of polarizing activity (ZPA)

Back 26

mesodermal cells at base of limb bud that direct organization of limb bud & patterning of digits, which involves retinoic acid & Hox-4

Front 27

Digit formation

Back 27

occurs as result of selected apoptosis within AER such that 5 separate regions of AER remain at tips of future digits

Front 28

Neurocranium devos from?

Back 28

neural crest cells except for basilar part of occipital bone region

Front 29

Basilar part of occipital bone devos from?

Back 29

Mesoderm cells of occipital sclerotomes

Front 30

Viserocranium

Back 30

bones of face involving pharyngeal arches , devos from neural crest cells except for laryngeal cartilages

Front 31

Laryngeal cartilages devo from?

Back 31

mesoderm within pharyngeal arches 4 & 6

Front 32

Sutures: define

Back 32

Dense connective tissue that separate flat bones of skull during fetal and infant life

Front 33

Sutures: List

Back 33

5: frontal, sagittal, lamboid, coronal & squamosal

Front 34

Sutures allow for?

Back 34

flat bones of skull to deform during childbirth ("molding") and expansion and growth of brain during infancy

Front 35

Define fontanelles

Back 35

Large fibrous areas where several sutures meet, a total of six

Front 36

Anterior Fontanelle

Back 36

Largest and readily palpable in infant; pulsates due to cerebral arteries; can be used for blood sample from superior sagittal sinus; closes at age 2

Front 37

Fontanelles: Close at age 2 years

Back 37

Anterior and the 2 mastoid fontanelles, because main growth of brain ceased

Front 38

Fontanelles: Close at age 6 months

Back 38

Posterior and 2 sphenoid fontanelles

Front 39

Craniosynostoses

Back 39

premature closure of sutures

Front 40

Microcephaly

Back 40

failure of brain to grow; mental retardation

Front 41

Oxycephaly (turricephaly/acrocephaly)

Back 41

tower-like skull caused by premature closure of lamboid & coronal sutures

Front 42

Crouzon's Syndrome

Back 42

Dominant genetic condition like oxycephaly, but accompanied w/ malformed face, teeth & ears

Front 43

Plagiocephaly

Back 43

asymmetric skull caused by premature closure of lambdoid & coronal sutures on 1 side of skull

Front 44

Scaphocephaly

Back 44

Long, narrow skull (in ant/post plane) caused by premature closure of sagittal suture

Front 45

Temporal Bone formation: Mastoid Process

Back 45

absent at birth, formed by age 2 yrs, leaving CN VII unprotected emerging from stylomastoid foramen; can be damaged in difficult delivery

Front 46

Temporal Bone formation:
Petrosquamous fissure

Back 46

Petrous & squamous portions of temporal bone separated by this; opens directly into middle ear, and may remian open until age 20 yrs, leaving route for infection spread from middle ear--> meninges

Front 47

Vertebral Column devos from?

Back 47

Mesodermal cells in sclerotome migrating & condensing around the notochord to form a centrum, around the neural tube to form vertebral arches and in the body wall to form costal processes

Front 48

Centrum

Back 48

mesodermal cells from sclerotomes that migrate and condense around notocord & form vertebral body of vertebrae

Front 49

Vertebral Arches

Back 49

mesodermal cells from sclerotomes that migrate and condense around the neural tube to form vertebral arches, which furhter devo into pedicles, laminae, spinous process, articular processes and transverse processes

Front 50

Costal Processes

Back 50

mesodermal cells from sclerotomes that migrate and condense around body wall to form costal processes, which further devo into the ribs

Front 51

Intersegmental Position of Vertebrae

Back 51

As mesodermal cells from scelrotome migrate toward notochord & neural tube, they split into cranial & caudal portions; important b/c allows developing spinal nerve a route of access to myotome it innervates

Front 52

Caudal Portion of sclerotome fuses with?

Back 52

fuses with cranial portion of succeeding sclerotome, which results in intersegmental position of vertebrae

Front 53

Formation of occipital bone

Back 53

Cervical region, caudal portion of 4th occipital sclerotome fuses w/ cranial portion of 1st cervical sclerotome,to form the base of the occipital bone; allows C1 spinal nerve to exit btwn base of bone & C1 vertebrae

Front 54

Nucleus Pulposus

Back 54

remnant of embryonic notochord; by 20 yrs, notochordal cells are degenerated & limited to a noncellular matrix only

Front 55

Annulus Fibrosus

Back 55

outerrim of fibrocartilage serived from mesoderm btwn vertebral bodies

Front 56

Congenital Brevicollis (Klippel-Feil Syndrome)

Back 56

Fusion & shortening of cervical vertebrae, associated w/ shortness of neck, low hairline, limited neck & head motion

Front 57

Intervertebrael Disk Herniation

Back 57

Prolapse of nucleus pulposus thru defective annulus fibrosus,nuc. pulp. impinges on spinal roots--> root pain, radiculopathy

Front 58

Spina Bifida Occulta

Back 58

Failure of vertebral arches to form or fuse

Front 59

Spondylolisthesis

Back 59

Pedicles of vertebral arches fail to fuse w/ vertebral body

Front 60

Hemivertebrae

Back 60

Wedges of vertebrae appear that are usually situated laterally btwn 2 other vertebrae

Front 61

Vertebral Bar

Back 61

Localized failure of segmentatin on 1 side of column, usu. posterolateral side

Front 62

Block Vertebrae

Back 62

Lack of separation btwn 2+ vert., usu in lumbar region

Front 63

Cleft Vertebrae

Back 63

Cleft devos in vertebrae, usu. in coronal/ sagittal plane in lumbar region

Front 64

Idiopathic Scoliosis

Back 64

Lateral deviation of vert column, involving both deviation and rotation of vert bodies

Front 65

Ribs devo

Back 65

costal processes only in thoracic region that grow into ribs; accessory most common & are attached to C7 vertebrae, either ending freely or attached to thoracic cage

Front 66

Superior Thoracic Outlet Syndrome

Back 66

Pressure on loer trunk of brachial plexsus & subclavian artery from accessory cervical ribs

Front 67

Sternum devo

Back 67

devos from 2 sternal bars that form in ventral wall independently; fuse w/ each other in cranial-caudal direction to form manibrium & xiphoid process at WK8

Front 68

Sternal Cleft

Back 68

sternal bars don't fuse completely; not a big problem

Front 69

Pectus Excavatum

Back 69

most common chest annom,; depression of chest wall that may extend from manibrium to xiphoid; CP restriction, dropped shoulders, protubernt abdomen, scoliosis; early surg intervention usu needed

Front 70

Poland Syndrome

Back 70

Partial/Complete absence of Pectoralis Major; may also have partial agenesis of ribs, ternum, mammary glands, absent lat dorsi & serratus anterior

Front 71

Devo of Limbs and Limb Girdles

Back 71

devo from condensations of lateral plate mesoderm in limb bud

Front 72

Limb Buds Timeline

Back 72

first visible by WK4, upper appears first, well diff. by WK8, limb tip contains Apical Ecotodermal Ridge, which is inductive to further devo

Front 73

Intramembraneous Ossification

Back 73

embryonic mesoderm condenses into sheets of highly vascular CT and directly forms primary ossifciation center; BONES: frontal, parietal, intraparietal of occipital, maxilla, zygomatic, squamous part of temporal, palatine, vomer & mandible

Front 74

Endochondral Ossification

Back 74

Embryonic mesoderm forst forms hyaline cartilage model, and THEN develops a primary ossification center at diaphysis; BONES:ethmoid, sphenoid & mastoid of temporal bone, basilar part of occipital bone, incus, malleus, stapes, styloid process, hyoid, bones of limbs, limb girdles, vertebrae, sternum & ribs

Front 75

Osteogenesis:

Back 75

occurs by replacement of preexisting CT (from mesoderm); Two types: intramembraneous (direct) and Endochondral (hyaline cartilage 1st)

Front 76

Describe how the expression of a gene is regulated

Back 76

-Binding of activators to cell membrane and initiation of various pathways resulting in a transcription cascade
-General transcription factors are recruited during the cascade and upon entering the nucleus, assemble with RNA Polymerase II and bind to the core promoter and enhancer regions of a gene

Front 77

Describe how a transcription factor increases gene expression.

Back 77

-General transcription factors assemble on all promoter regions transcribed by RNA polymerase II, and are not specified to a specific gene
-Specific transcription factors (enhancer binding proteins) bind to the enhancer sub-region in the promoter region of a specific gene
-Co-activators and mediators act to decondense chromatin nucleosomes and allow for transcription factors to gain access to specific promoters

Front 78

Describe how the secreted protein BMP4 induces gene expression

Back 78

-Bone Morphogenetic Protein-4 binds to ectodermal cells and activates expression of genes which promote epidermal specific genes
-Activation of epidermal genes inhibits the expression of neural specific genes, which are only activated/expressed when BMP4 is absent
-BMP4 (Transforming Growth Factor-β superfamily) activates the SMAD family of transcription factors by binding type II TGF-β receptors
-Phosphorylated SMAD proteins enter the nucleus and bind to the enhancer sub-region in the promoter region of the epidermal tissue gene
-Noggin, chordin and follistatin promote neuronal differentiation by inhibiting the binding of BMP4 to the ectoderm

Front 79

Describe how retinoic acid gradient specifies rostral-caudal axis formation.

Back 79

-Rostral-caudal axis formation is regulated by transcription factors that are encoded for by the HOX (homeobox) gene
-Retinoic acid diffuses through cell membranes and binds retinoic acid receptors, then enter the nucleus to act as a transcription factor
-Retinoic acid bound receptors then bind to specific enhancer elements (retinoic acid response elements) in the promoter region of the HOX gene
-HOX genes are present in clusters in the chromosome and have varying degrees are response time and sensitivity to retinoic acid
-The retinoic acid gradient (anterior-posterior) provides concentration variation that activates HOX genes at different times/intensity resulting in limb bud formation
-Mutation of specific HOX genes can leads to increased/decreased retinoic acid sensitivity, resulting in synpolydactyly

Front 80

Discuss how sonic hedgehog gradient specifies dorsal-ventral axis formation.

Back 80

-Sonic hedgehog binds cell surface receptors that activate the transcription factor Gli (cubitus interruptus), which enters the nucleus and acts as a transcriptional activator of specific neuronal genes
-The sonic hedgehog gradient provides concentration variation that activates specific genes at different times/intensity resulting in motor neuron differentiation
-Cholesterol is present on the sonic hedgehog protein and plays an important role in cell signaling and activation of Gli
-Mutation of either the genes that encode for sonic hedgehog or the enzymes that synthesize cholesterol can cause cyclopia

Front 81

Discuss how teratogens can alter development

Back 81

-Environmental agents that disrupt normal fetal development
-Retinoic acid (Accutane – vitamin A) used to treat severe acne can cause expression of certain HOX genes in cells that do not normally express that gene, resulting in severe hind/mid/fore-brain abnormalities
-Thalidomide used as a mild sedative that can inhibit angiogenesis, resulting in various abnormalities to include; limb deformation, heart defects, malformed intestines and missing external ears

Front 82

Describe how blood vessels are formed

Back 82

-Hemangioblasts (blood vessel and blood cell precusor) are exposed to high concentrations of BPMs early in development and give rise to angioblasts (vascular endothelial cell and hematopoietic stem cell precursor)
-Hematopoietic stem cells are exposed to erythropoietin and differentiate into red blood cells, or lymphocytes with not erythropoietin exposure
-Vasculogenesis is the de novo creation of blood vessels from lateral plate mesoderm
-Angiogenesis is creation blood vessels via vascular endothelial growth factor (VEGF), which binds receptors on endothelial cells and induces increased expression of genes whose specific protein products are necessary for angiogenesis
-Inhibitors of VEGF (Avastin) can be used to treat various types of cancers

Front 83

Differention

Back 83

-How different genes from the same genetic repertoire are activated at a particular time and place in response to exposure to gradients of molecules or proteins to cause cells to become different from one another

Front 84

Morphogens

Back 84

-Diffusible molecules that form time-dependent concentration gradients to specify which cell type will be generated at a specific location
-cell fate can be determined by its location along these gradients, and the set of receptors expressed on their cell surface
-ex: retinoic acid (RA), bone morphogenic proteins (BMPs), transforming growth factor beta (TGF-Beta), hedgehogs, & Wnt protein families

Front 85

Gastrulation

Back 85

-Process of cell movements by which three germ layers and axial orientation are established in embryos
-First sign: appearance of the primitive streak
-End: embryo becomes surrounded by ectoderm, endoderm is internalized, and mesoderm betwwn the ectoderm and endoderm.
-embryonic ectoderm: epidermis, CNS, PNS, retina, eye, etc.
-ex: specific morphogens secreted by the primitive streak alter expression of genes in the overlying ectodermal cells turning them into neural precursor cells.

Front 86

Coding Region of a Gene

Back 86

-specifies the amino acid sequence of resulting protein

Front 87

Promoter Region of Gene

Back 87

-controls how many RNA copies are made

Front 88

Core promoter (part of Promoter Region in Gene)

Back 88

-a specific DNA sequence to which RNA polymerase II binds and initiates transcription (or RNA synthesis).
-aka TATA box
-RNA pol II can't bind on its own, needs general trascription factors to help it
-Once RNA pol is bound it has to be released to start making RNA.So TFIIH (transcription factor)adds phosphate groups to the RNA polymerase to help release it from the DNA promoter and TF cluster, allowing transcription to start
-Core promoter by itself makes RNA because RNA pol II and general TFs can't assemble on a promoter associated w/ histone proteins
*clinical*: gene for 1st subunit of TFIIH was cloned from humans bc mutations in this gene cause extreme skin sensitivity to sunlight (common cause of DNA damage) & exhibits high incidence of cancer; may cause diseases like xeroderma pigmentosa and Cockayne's syndrome

Front 89

Define mesenchyme

Back 89

Refers to loosely organized connective tissue present in the embryo regardless of origin. Mesenchyme later differentiates into blood vessels, blood-related organs, and connective tissues.
Embryonic connective tissue (mesenchyme):
• Consists of loosely-packed, unspecialized cells set in a gelatinous extracellular matrix
• Develops into other types of tissues: connective, bone, cartilage
• Develops into other types of structures and systems: blood cells, endothelial cells, smooth muscle cells, circulatory system, lymphatic system.
All organs in the body contain mesenchyme.

Front 90

Define ectomesenchyme

Back 90

Ectomesenchyme has similar properties to mesenchyme. The major difference is that ectomesenchyme is usually considered to arise from neural crest cells,[2] which are a critical group of cells that form in the cranial region during early vertebrate development. Thus, ectomesenchyme plays a critical role in the formation of the hard and soft tissues of the head and neck such as bones, muscles and most importantly the branchial arches.

Front 91

How is mesenchyme different than mesoderm?

Back 91

Mesenchyme is not necessarily of mesodermal origin (can also be derived from neural crest cells of ectoderm, as ectomesenchyme); it is loosely orgainized CT in embryo, regardless of origin; Mesoderm is one of the three embryonic germ layers that devos into:
bones
most of the circulatory system, including the heart and major blood vessels
connective tissues of the gut and integuments
mesenchyme
mesothelium
muscles
peritoneum (lining of the coelom)
reproductive system
urinary system, including the kidneys

Front 92

Enhancer (part of promoter region in gene)

Back 92

-DNA sequence(s) to which TFs (aka enhancer binding proteins) bind to increase transcription (gene expression)
-used for enhancement of mRNA synthesis

Front 93

Transcription Factors

Back 93

-Proteins with 2 segments or domains: DNA binding and activation
-amino acids in the DNA binding domain interact w/specific enhancer sequences