Chapter 17: Head and Neck Flashcards by Secret acc

Mesenchyme for formation of the head region is derived from ______ and ______, ______, and thickened regions of ______ known as ______.

paraxial, lateral plate mesoderm, neural crest, ectoderm, ectodermal placodes

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Paraxial mesoderm (______ and ______) forms a large portion of the ______ and ______ components of the ______ (______), all ______ muscles of the ______ region, the ______ and ______ tissues in the ______ region of the head, and the ______ caudal to the ______. Lateral plate mesoderm forms the ______ (______ and ______) and ______ tissue in this region.

somites, somitomeres, membranous, cartilaginous, neurocranium, skull, voluntary, craniofacial, dermis, connective, dorsal, meninges, prosencephalon, laryngeal cartilages, arytenoid, cricoid, connective

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Neural crest cells originate in the ______ of ______, ______, and ______ regions and migrate ______ into the ______ and ______ around the ______ and ______ into the facial region.

neuroectoderm, forebrain, midbrain, hindbrain, ventrally, pharyngeal arches, rostrally, forebrain, optic cup

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In these locations, they form the entire ______ (______) and parts of the ______ and ______ regions of the ______ (______). They also form all other tissues in these regions, including ______, ______, ______, ______, ______, ______ and ______, sensory ______, and glandular ______ tissue.

viscerocranium, face, membranous, cartilaginous, neurocranium, skull, cartilage, bone, dentin, tendon, dermis, pia, arachnoid, neurons, connective

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Cells from ectodermal placodes (______), together with ______, form neurons of the ______, ______, ______, and ______ cranial sensory ganglia.

epipharyngeal placodes, neural crest, 5th, 7th, 9th, 10th

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The most distinctive feature in development of the head and neck is the presence of ______ (the old term for these structures is ______ because they somewhat resemble the gills [branchia] of a fish). These arches appear in the ______ and ______ weeks of development and contribute to the characteristic external appearance of the ______. Initially, they consist of bars of ______ tissue separated by deep clefts known as ______.

pharyngeal arches, branchial arches, fourth, fifth, embryo, mesenchymal, pharyngeal clefts

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Simultaneously, with development of the arches and clefts, a number of outpocketings, the ______, appear along the ______ walls of the ______, the most ______ part of the ______.

pharyngeal pouches, lateral, pharynx, cranial, foregut

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The pouches penetrate the surrounding ______ but do not establish an open communication with the external ______. Hence, although development of pharyngeal arches, clefts, and pouches resembles formation of ______ in fishes and amphibians, in the human embryo, real ______ are never formed.

mesenchyme, clefts, gills, gills

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Therefore, the term ______ (arches, clefts, and pouches) has been adopted for the human embryo.

pharyngeal

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Pharyngeal arches not only contribute to formation of the ______ but also play an important role in formation of the ______.

neck, face

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At the end of the ______ week, the center of the face is formed by the ______, surrounded by the first pair of ______.

fourth, stomodeum, pharyngeal arches

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When the embryo is ______ days old, five mesenchymal prominences can be recognized: the ______ (first pharyngeal arch), ______ to the ______, the ______ (dorsal portion of the first pharyngeal arch), ______ to the ______, and the ______, a slightly rounded elevation ______ to the ______.

42, paired mandibular prominences, caudal, stomodeum, paired maxillary prominences, lateral, stomodeum, frontonasal prominence, cranial, stomodeum

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Development of the face is later complemented by formation of the ______. In all cases, differentiation of structures derived from arches, pouches, clefts, and prominences is dependent on ______.

nasal prominences, epithelial–mesenchymal interactions

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PHARYNGEAL ARCHES

Each pharyngeal arch consists of a ______ of ______ covered on the outside by surface ______ and on the inside by ______ of ______ origin.

core, mesenchymal tissue, ectoderm, epithelium, endodermal

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PHARYNGEAL ARCHES

In addition to mesenchyme derived from ______ and ______ plate mesoderm, the ______ of each arch receives substantial numbers of ______, which migrate into the ______ to contribute to ______ components of the face.

paraxial, lateral, core, neural crest cells, arches, skeletal

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PHARYNGEAL ARCHES

The original mesoderm of the arches gives rise to the musculature of the ______ and ______. Thus, each ______ is characterized by its own ______ components.

face, neck, pharyngeal arch, muscular

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PHARYNGEAL ARCHES

The muscular components of each arch have their own ______, and wherever the ______ cells migrate, they carry their ______ component with them.

cranial nerve, muscle, nerve

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PHARYNGEAL ARCHES

In addition, each arch has its own ______ component.

arterial

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First Pharyngeal Arch

The ______ consists of a ______ portion, the ______, which extends forward beneath the region of the ______, and ______ portion, the ______, which contains ______.

first pharyngeal arch, dorsal, maxillary process, eye, aventral, mandibular process, Meckel cartilage

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First Pharyngeal Arch

During further development, ______ disappears except for ______ small portions at its ______ end that persist and form the ______ and ______.

Meckel cartilage, two, dorsal, incus, malleus

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First Pharyngeal Arch

Mesenchyme of the maxillary process gives rise to the ______, ______, ______, and part of the ______ through ______.

premaxilla, maxilla, zygomatic bone, temporal bone, membranous ossification

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First Pharyngeal Arch

The mandible is also formed by ______ of ______ surrounding ______. In addition, the ______ arch contributes to formation of the bones of the ______, part of the ______, and the ______.

membranous ossification, mesenchymal tissue, Meckel cartilage, first, middle ear, external ear, external auditory meatus

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First Pharyngeal Arch

Musculature of the first pharyngeal arch includes the ______ (______, ______, and ______), anterior belly of the ______, ______, ______, and ______.

muscles of mastication, temporalis, masseter, pterygoids, digastric, mylohyoid, tensor tympani, tensor palatini

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First Pharyngeal Arch

Hie nerve supply to the muscles of the first arch is provided by the ______ of the ______.

mandibular branch, trigeminal nerve

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First Pharyngeal Arch Because mesenchyme from the first arch also contributes to the ______ of the face, sensory supply to the skin of the face is provided by ______, ______, and ______ branches of the ______.

dermis, ophthalmic, maxillary, mandibular, trigeminal nerve

First Pharyngeal Arch Muscles of the arches do not always attach to the ______ or ______ components of their own arch but sometimes ______ into surrounding regions. Nevertheless, the origin of these muscles can always be ______ because their nerve supply is derived from the ______ of ______.

bony, cartilaginous, migrate, traced, arch, origin

Second Pharyngeal Arch The cartilage of the ______ or ______ arch (______) gives rise to the ______, ______ of the ______, ______, and ______, the ______ and upper part of the body of the ______.

second, hyoid, Reichert cartilage, stapes, styloid process, temporal bone, stylohyoid ligament, ventrally, lesser horn, hyoid bone

Second Pharyngeal Arch Mesenchyme of the arch also forms most of the ______.

external ear

Second Pharyngeal Arch Muscles of the hyoid arch are the ______, ______, ______ of the ______, ______, and muscles of ______.

stapedius, stylohyoid, posterior belly, digastric, auricular, facial expression

Second Pharyngeal Arch The ______, the nerve of the second arch, supplies all of these muscles.

facial nerve

Third Pharyngeal Arch The cartilage of the ______ produces the ______ of the body and ______ of the hyoid bone.

third pharyngeal arch, lower part, greater horn

Third Pharyngeal Arch The musculature is limited to the ______. These muscles are innervated by the ______, the nerve of the third arch.

stylopharyngeus muscles, glossopharyngeal nerve

Fourth and Sixth Pharyngeal Arches ______ components of the ______ and ______ pharyngeal arches fuse to form the ______, ______, ______, ______, and ______ cartilages of the ______.

Cartilaginous, fourth, sixth, thyroid, cricoid, arytenoid, corniculate, cuneiform, larynx

Fourth and Sixth Pharyngeal Arches Muscles of the ______ arch (______, ______, and constrictors of the ______) are innervated by the ______ branch of the ______, the nerve of the fourth arch.

fourth, cricothyroid, Levato veli palatini, pharynx, superior laryngeal, vagus

Fourth and Sixth Pharyngeal Arches Intrinsic muscles of the larynx are supplied by the ______ branch of the ______, the nerve of the sixth arch.

recurrent laryngeal, vagus

PHARYNGEAL POUCHES The human embryo has ______ pairs of pharyngeal pouches; the ______ is rudimentary.

four, fifth

PHARYNGEAL POUCHES Because the ______ of the pouches gives rise to a number of important organs, the fate of each pouch is discussed separately.

epithelial endodermal lining

First Pharyngeal Pouch The ______ forms a stalklike diverticulum, the ______, which comes in contact with the ______ of the ______.

first pharyngeal pouch, tubotympanic recess, epithelial lining, first pharyngeal cleft

First Pharyngeal Pouch The ______ portion of the diverticulum widens into a saclike structure, the ______ or ______, and the ______ part remains narrow, forming the ______ (______) tube.

distal, primitive tympanic, middle ear cavity, proximal, auditory, eustachian

First Pharyngeal Pouch The lining of the tympanic cavity later aids in formation of the ______ or ______.

tympanic membrane, eardrum

Second Pharyngeal Pouch The ______ of the second pharyngeal pouch proliferates and forms ______ that penetrate into the surrounding ______.

epithelial lining, buds, mesenchyme

Second Pharyngeal Pouch The buds are secondarily invaded by ______, forming the ______ of the ______.

mesodermal tissue, primordium, palatine tonsils

Second Pharyngeal Pouch During the ______ and ______ months, the tonsil is infiltrated by ______ tissue. Part of the pouch remains and is found in the adult as the ______.

third, fifth, lymphatic, tonsillar fossa

Third Pharyngeal Pouch The ______ and ______ pouches are characterized at their distal extremity by a ______ and a ______ wing.

third, fourth, dorsal, ventral

Third Pharyngeal Pouch In the ______ week, epithelium of the ______ region of the third pouch differentiates into the ______, whereas the ______ region forms the ______. Both gland ______ lose their connection with the pharyngeal wall, and the ______ then migrates in a ______ and a ______ direction, pulling the ______ with it.

fifth, dorsal, inferior parathyroid gland, ventral, thymus, primordia, thymus, caudal, medial, inferior parathyroid

Third Pharyngeal Pouch Although the main portion of the thymus moves rapidly to its final position in the ______ part of the ______ where it fuses with its counterpart from the ______ side, its ______ portion sometimes persists either embedded in the ______ or as isolated ______.

anterior, thorax, opposite, tail, thyroid gland, thymic nests

Third Pharyngeal Pouch Growth and development of the ______ continue until puberty.

thymus

Third Pharyngeal Pouch In the young child, the thymus occupies considerable space in the ______ and lies behind the ______ and ______ to the ______ and ______. In older persons, it is difficult to recognize because it is ______ and replaced by ______.

thorax, sternum, anterior, pericardium, great vessels, atrophied, fatty tissue

Third Pharyngeal Pouch The parathyroid tissue of the third pouch finally comes to rest on the ______ surface of the ______ and forms the ______.

atrophieddorsal, thyroid gland, inferior parathyroid gland

Fourth Pharyngeal Pouch Epithelium of the ______ region of the ______ forms the ______.

dorsal, fourth pharyngeal pouch, superior parathyroid gland

Fourth Pharyngeal Pouch When the parathyroid gland loses contact with the wall of the pharynx, it attaches itself to the ______ surface of the caudally migrating ______ as the ______.

dorsal, thyroid, superior parathyroid gland

Fourth Pharyngeal Pouch The ventral region of the fourth pouch gives rise to the ______, which is later incorporated into the ______.

ultimobranchial body, thyroid gland

Fourth Pharyngeal Pouch Cells of the ultimobranchial body give rise to the ______, or ______, of the ______. These cells secrete ______, a hormone involved in regulation of the ______ in the blood.

parafollicular cells, C cells, thyroid gland, calcitonin, calcium level

PHARYNGEAL CLEFTS The ______-week embryo is characterized by the presence of ______ pharyngeal clefts.

5, four

PHARYNGEAL CLEFTS Previously, it was thought that the ______ cleft contributed the ______ of the ______, but this claim has been disproved.

first, external auditory meatus (EAM), external ear

PHARYNGEAL CLEFTS Instead, the EAM forms by invagination of surface ______ from the ______.

ectoderm, first pharyngeal arch

PHARYNGEAL CLEFTS Overgrowth of the ______ arch, as it forms most of the ______, causes the ______ to disappear.

second, external ear, first cleft

PHARYNGEAL CLEFTS Active proliferation of ______ tissue in the second ______ causes it to overlap the ______ and ______ arches. Finally, it merges with the ______ in the ______ part of the ______, and the ______, ______, and ______ clefts lose contact with the ______.

mesenchymal, arch, third, fourth, epicardial ridge, lower, neck, second, third, fourth, outside

PHARYNGEAL CLEFTS The clefts form a cavity lined with ectodermal epithelium, the ______, but with further development, this sinus disappears.

cervical sinus

MOLECULAR REGULATION OF FACIAL DEVELOPMENT Neural crest cells arise from ______ adjacent to the surface ______ all along the edges of the ______.

neuroepithelial cells, ectoderm, neural folds

MOLECULAR REGULATION OF FACIAL DEVELOPMENT ______ signaling is important in establishing this edge region and then regulates ______ expression to cause prospective crest cells to undergo an ______ and begin their migration into the surrounding ______.

Bone morphogenetic protein (BMP), WNT1, epithelial-to-mesenchymal transition, mesenchyme

MOLECULAR REGULATION OF FACIAL DEVELOPMENT In the hindbrain, crest cells originate in a specific pattern from segments called ______. There are ______ of these segments in the hindbrain (______—______), and neural crest cells from specific segments migrate to populate specific ______.

rhombomeres, eight, R1, R8, pharyngeal arches

MOLECULAR REGULATION OF FACIAL DEVELOPMENT These crest cells migrate in ______ streams: Those from ______ and ______ migrate to the first arch along with crest cells from the caudal midbrain region, crest from ______ migrate to the second arch, and cells from ______ and ______ migrate to arches 4 to 6.

three, R1, R2, R4, R6, R7

MOLECULAR REGULATION OF FACIAL DEVELOPMENT Segregation of the three streams is assisted by the fact that very few crest cells form from ______ and ______ segments and those that do enter adjoining streams of cells to migrate.

R3, R5

MOLECULAR REGULATION OF FACIAL DEVELOPMENT Three distinct streams are important because they provide axonal guidance cues for ______ from ______ forming in the ______ and ______ region, including the ______, ______, ______, ______, and ______ ganglia. These ganglia are formed from a combination of ______ and cells from ______ in this region.

axons, ganglia, head, neck, trigeminal, geniculate, vestibuloacoustic, petrosal, nodose, crest cells, placodes

MOLECULAR REGULATION OF FACIAL DEVELOPMENT Axons from the ______ ganglion enter the hindbrain at R2, those from the ______ and ______ at R4, and those from the ______ and ______ at R6 and R7, thus accounting for three streams of crest cells.

trigeminal, geniculate, vestibuloacoustic, petrosal, nodose

MOLECULAR REGULATION OF FACIAL DEVELOPMENT No axons project to ______ or ______.

R3, R5

MOLECULAR REGULATION OF FACIAL DEVELOPMENT Neural crest cells that populate the pharyngeal arches form the ______ components characteristic of each arch.

skeletal

MOLECULAR REGULATION OF FACIAL DEVELOPMENT Previously, it was thought that ______ regulated patterning of these skeletal elements, but now, it is clear that this process is controlled by ______.

neural crest cells, pharyngeal pouch endoderm

MOLECULAR REGULATION OF FACIAL DEVELOPMENT Formation of the pharyngeal pouches occurs prior to ______ and takes place even in the absence of ______.

neural crest migration, crest cells

MOLECULAR REGULATION OF FACIAL DEVELOPMENT Pouches are formed by migration of ______ cells ______, and this migration is stimulated by ______.

endoderm, laterally, fibroblast growth factors (FGFs)

MOLECULAR REGULATION OF FACIAL DEVELOPMENT As pouches form, they express a very characteristic pattern of genes. ______ is expressed in the posterior endoderm of each pouch, ______ lies in the anterior endoderm, and ______ expression is restricted to the dorsalmost endoderm of each pouch.

BMP7, FGF8, PAX1

MOLECULAR REGULATION OF FACIAL DEVELOPMENT In addition, ______ is expressed in the posterior endoderm of the ______ and ______ pouches.

SONIC HEDGEHOG (SHH), second, third

MOLECULAR REGULATION OF FACIAL DEVELOPMENT These expression patterns then regulate diiferentiation and patterning of pharyngeal arch ______ into specific ______ structures. This process, however, is also dependent on the ______ and represents another example of an ______ interaction. In this case, the response of the mesenchyme to endodermal signals is dependent on ______ expressed in that mesenchyme.

mesenchyme, skeletal, mesenchyme, epithelial—mesenchymal, transcription factors

MOLECULAR REGULATION OF FACIAL DEVELOPMENT These transcription factors include ______ and others carried by ______ cells into the arches. Crest cells acquire their specific gene expression patterns from the ______ of their origin.

HOX genes, neural crest, rhombomeres

MOLECULAR REGULATION OF FACIAL DEVELOPMENT The pattern of rhombomeres itself is established by a nested code of ______ expression in the ______ that ______ carry with them when they migrate.

HOX gene, hindbrain, crest cells

MOLECULAR REGULATION OF FACIAL DEVELOPMENT The first arch is ______ but does express ______, a homeodomain-containing transcription factor that is expressed in the midbrain; the second arch expresses ______; and arches 3 to 6 express members of the ______ paralogous group of ______ genes, ______, ______, and ______.

HOX-negative, OTX2, HOXA2, third, HOX, HOXA3, HOXB3, HOXD3

MOLECULAR REGULATION OF FACIAL DEVELOPMENT The different expression patterns of these transcription factors allow each arch to respond differently to signals emanating from ______, such that the ______ arch forms the ______ and ______, the ______ arch, the ______ bone, etc.

pouch endoderm, first, maxilla, mandible, second, hyoid

MOLECULAR REGULATION OF FACIAL DEVELOPMENT The remainder of the skeleton of the face, the mid and upper facial regions, also is derived from ______ that migrate into the ______. In this region, signals emanating from the surface ______ and the underlying areas of the ______ dictate the fate of the mesenchyme.

neural crest cells, frontonasal prominence, ectoderm, neuroepithelium

MOLECULAR REGULATION OF FACIAL DEVELOPMENT Again, it appears that ______ and ______ play major roles in patterning this area, but the specific genetic interactions are not known.

SHH, FGF8

Clinical Correlates Birth Defects Involving the Pharyngeal Region Ectopic Thymic and Parathyroid Tissue Because ______ tissue derived from the pouches undergoes migration, it is not unusual for accessory glands or remnants of tissue to persist along the pathway. This is true particularly for ______ tissue, which may remain in the ______, and for the ______. The ______ are more variable in position than the ______ ones and are sometimes found at the bifurcation of the ______.

glandular, thymic, neck, parathyroid glands, inferior parathyroids, superior, common carotid artery

Clinical Correlates Birth Defects Involving the Pharyngeal Region ______ occur when the second pharyngeal arch fails to grow caudally over the third and fourth arches, leaving remnants of the second, third, and fourth clefts in contact with the surface by a narrow canal.

Branchial fistulas

Clinical Correlates Birth Defects Involving the Pharyngeal Region Branchial FistuIas Such a fistula, found on the lateral aspect of the neck directly anterior to the ______ muscle, usually provides drainage for a ______. These cysts, remnants of the cervical sinus, are most often just below the angle of the ______, although they may be found anywhere along the anterior border of the ______ muscle. Frequently, a ______ is not visible at birth but becomes evident as it enlarges during childhood.

sternocleidomastoid, lateral cervical cyst, jaw, sternocleidomastoid, lateral cervical cyst

Clinical Correlates Birth Defects Involving the Pharyngeal Region Branchial FistuIas ______ are rare; they occur when the cervical sinus is connected to the lumen of the pharynx by a small canal, which usually opens in the tonsillar region. Such a fistula results from a rupture of the membrane between the ______ and ______ at some time during development.

Internal branchial fistulas, second pharyngeal cleft, pouch

Clinical Correlates Birth Defects Involving the Pharyngeal Region Neural Crest Cells and Craniofacial Defects ______ are essential for formation of much of the craniofacial region. Consequently, disruption of crest cell development results in craniofacial malformations.

Neural crest cells

Clinical Correlates Birth Defects Involving the Pharyngeal Region Neural Crest Cells and Craniofacial Defects Because neural crest cells also contribute to the ______, which septate the outflow tract of the heart into pulmonary and aortic channels, many infants with craniofacial defects also have cardiac abnormalities, including persistent ______, ______, and transposition of the ______.

conotruncal endocardial cushions, truncus arteriosus, tetralogy of Fallot, great vessels

Clinical Correlates Birth Defects Involving the Pharyngeal Region Neural Crest Cells and Craniofacial Defects Unfortunately, crest cells appear to be a particularly vulnerable cell population and are easily killed by compounds such as ______ and ______.

alcohol, retinoic acid

Clinical Correlates Birth Defects Involving the Pharyngeal Region Neural Crest Cells and Craniofacial Defects Examples of craniofacial defects involving crest cells include the following:

1. Treacher Collins syndrome [mandibulofacial dysostosis] 2. Robin sequence 3. 22q11.2 Deletion syndrome 4. Hemifacial microsomia [oculoauriculovertebral spectrum or Goldenhar syndrome]

Clinical Correlates Birth Defects Involving the Pharyngeal Region Neural Crest Cells and Craniofacial Defects ______ is a rare autosomal dominant disorder occurring in 1/50,000 live births with 60% of cases arising as new mutations. The syndrome is characterized by hypoplasia of the maxilla, mandible, and zygomatic arches, which may be absent. Cleft palate is common as are external ear defects accompanied by atresia of the auditory canals and abnormalities of the middle ear ossicles, such that bilateral conductive hearing loss is often present. The eyes are usually involved with down-slanting palpebral fissures and lower eyelid colobomas. Mutations in the ______ gene [5q32] are responsible for most cases. The product of this gene is a nucleolar protein called ______ that appears to be necessary for preventing apoptosis and maintaining proliferation in neural crest cells but not for regulating their migration, which occurs normally. Although most cases of the syndrome are due to genetic mutations, phenocopies can be produced in laboratory animals following exposure to teratogenic doses of retinoic acid, suggesting that some cases in humans may be caused by teratogens.

Treacher Collins syndrome [mandibulofacial dysostosis], TCOF1, treacle

Clinical Correlates Birth Defects Involving the Pharyngeal Region Neural Crest Cells and Craniofacial Defects ______ may occur independently or in association with other syndromes and malformations. Like Treacher Collins syndrome, it alters first-arch structures, with development of the mandible most severely affected. Infants usually have a triad of micrognathia, cleft palate, and glossoptosis [posteriorly placed tongue].

Robin sequence

Clinical Correlates Birth Defects Involving the Pharyngeal Region Neural Crest Cells and Craniofacial Defects ______ may be due to genetic or environmental factors. It may also occur as a deformation, as for example, when the chin is compressed against the chest in cases of oligohydramnios. The primary defect includes poor growth of the mandible and, as a result, a posteriorly placed tongue that fails to drop from between the palatal shelves, preventing their fusion. This occurs in approximately1/8,500 births.

Robin sequence

Clinical Correlates Birth Defects Involving the Pharyngeal Region Neural Crest Cells and Craniofacial Defects ______ is the most common deletion syndrome in humans and has several presentations, including DiGeorge syndrome, DiGeorge anomaly, velocardiofacial syndrome, Shprintzen syndrome, conotruncal anomaly face syndrome, and congenital thymic aplasia and hypoplasia. The defects are the result of a deletion on the long arm of chromosome 22 and occur in ap- proximately1 per 4,000 births. Recent evidence shows that mutations in one of the genes in the deletion interval, TBX1 [T—box DNA binding transcription factor 1], result in the same syn- drome without a deletion. Furthermore, variability in regulation of the TBX1 gene may explain the wide range of observed phenotypes. The syndrome is characterized by a variety of malformations and degrees of severity, but infants most often present with congenital heart and aortic arch defects, mild facial dysmorphology, learning disabilities, and frequent infections due to thymic hypoplasia or aplasia that disrupts the immune system’s T cell—mediated response. Many of the infants also have seizures clue to hypocalcemia caused by abnormal development of the parathyroid glands. Later in life, these individuals are more likely to have mental illnesses, including schizophrenia and depression. In part, origin of the defects is due to disruption of neural crest cells that contribute to many of the affected structures. Even the thymus and parathyroid defects are related to neural crest cells because these cells contribute the mesenchyme into which endoderm from the pharyngeal pouches migrates. Endoderm cells from the pouches make the thymus and parathyroid cells and neural crest derived mesenchyme makes the connective tissue. Without this mesenchyme, the normal epithelial [endo-dermal]-mesenchymal interaction essential for differentiation of the glands does not occur.

22q11.2 Deletion syndrome

Clinical Correlates Birth Defects Involving the Pharyngeal Region Neural Crest Cells and Craniofacial Defects ______ includes a number of craniofacial abnormalities that usually involve the maxillary, temporal, and zygomatic bones, which are small and flat. Ear [anotia, microtia], eye [tumors and dermoids in the eyeball], and vertebral [fused and hemivertebrae, spina bifida] defects are commonly observed in these patients. Asymmetry is present in 65% of the cases, which occur in 1/5,600 births. 0ther malformations, which occur in 50% of cases, include cardiac abnormalities, such as tetralogy of Fallot and ventricular septal defects. Causes of this are unknown.

Hemifacial microsomia [oculoauriculovertebral spectrum or Goldenhar syndrome]

TONGUE The tongue appears in embryos of approximately ______ weeks in the form of two ______ and one ______, the ______. These three swellings originate from the ______.

4, lateral lingual swellings, medial swelling, tuberculum impar, first pharyngeal arch

TONGUE A second median swelling, the ______, or ______, is formed by ______ of the ______, ______, and part of the ______ arch.

copula, hypobranchial eminence, mesoderm, second, third, fourth

TONGUE Finally, a third median swelling, formed by the ______ part of the ______ arch, marks development of the ______. Immediately behind this swelling is the ______, which is flanked by the ______.

posterior, fourth, epiglottis, laryngeal orifice, arytenoid swellings

TONGUE As the lateral lingual swellings increase in size, they overgrow the ______ and merge, forming the ______, or ______, of the tongue. Because the mucosa covering the body of the tongue originates from the ______, sensory innervation to this area is by the ______ of the ______. The body of the tongue is separated from the posterior third by a V-shaped groove, the ______.

tuberculum impar, anterior two-thirds, body, first pharyngeal arch, mandibular branch, trigeminal nerve, terminal sulcus

TONGUE The posterior part, or root, of the tongue originates from the ______, ______, and parts of the ______ pharyngeal arch. The fact that sensory innervation to this part of the tongue is supplied by the ______ indicates that tissue of the ______ arch overgrows that of the ______.

second, third, fourth, glossopharyngeal nerve, third, second

TONGUE The epiglottis and the extreme posterior part of the tongue are innervated by the ______, reflecting their development from the ______ arch. Some of the tongue muscles probably differentiate in situ, but most are derived from ______ originating in ______. Thus, tongue musculature is innervated by the ______.

superior laryngeal nerve, fourth, myoblasts, occipital somites, hypoglossal nerve

TONGUE The general sensory innervation of the tongue is easy to understand. The body is supplied by the ______, the nerve of the ______ arch; that of the root is supplied by the ______ and ______ nerves, the nerves of the ______ and ______ arches, respectively.

trigeminal nerve, first, glossopharyngeal, vagus, third, fourth

TONGUE ______ (taste) to the anterior two-thirds of the tongue is provided by the ______ branch of the ______, whereas the posterior third is supplied by the ______.

Special sensory innervation, chorda tympani, facial nerve, glossopharyngeal nerve

Clinical Correlates In ______ [______], the tongue is not freed from the floor of the mouth. Normally, extensive cell degeneration occurs, and the frenulum is the only tissue that anchors the tongue to the floor of the mouth. In the most common form of this, the frenulum extends to the tip of the tongue.

ankyloglossia, tongue-tie

THYROID GLAND The thyroid gland appears as an epithelial proliferation in the floor of the ______ between the ______ and the ______ at a point later indicated by the ______. Subsequently, the thyroid descends in front of the ______ as a ______. During this migration, the thyroid remains connected to the tongue by a narrow canal, the ______. This duct later disappears.

pharynx, tuberculum impar, copula, foramen cecum, pharyngeal gut, bilobed diverticulum, thyroglossal duct

THYROID GLAND With further development, the thyroid gland descends in front of the ______ and the ______. It reaches its final position in front of the ______ in the ______ week. By then, it has acquired a small median ______ and two lateral ______.

hyoid bone, laryngeal cartilages, trachea, seventh, isthmus, lobes

THYROID GLAND The thyroid begins to function at approximately the end of the ______ month, at which time the first follicles containing ______ become visible. ______ produce the colloid that serves as a source of ______ and ______.

third, colloid, Follicular cells, thyroxine, triiodothyronine

THYROID GLAND ______, or ______, derived from the ______ serve as a source of calcitonin.

Parafollicular cells, C cells, ultimobranchial body

Clinical Correlates Thyroglossal Duct and Thyroid Abnormalities A ______ may lie at any point along the migratory pathway of the thyroid gland but is always near or in the midline of the neck. As indicated by its name, it is a cystic remnant of the thyroglossal duct. Although approximately 50% of these cysts are close to or just inferior to the body of the hyoid bone, they may also be found at the base of the tongue or close to the thyroid cartilage.

thyroglossal cyst

Clinical Correlates Thyroglossal Duct and Thyroid Abnormalities Sometimes, a thyroglossal cyst is connected to the outside by a fistulous canal, a ______. Such a fistula usually arises secondarily after rupture of a cyst but may be present at birth.

thyroglossal fistula

Clinical Correlates Thyroglossal Duct and Thyroid Abnormalities ______ may be found anywhere along the path of descent of the thyroid gland. It is commonly found in the base of the tongue, just behind the foramen cecum, and is subject to the same diseases as the thyroid gland itself.

Aberrant thyroid tissue

FACE At the end of the ______ week, ______ consisting primarily of neural crest—derived mesenchyme and formed mainly by the first pair of pharyngeal arches appear.

fourth

FACE ______ can be distinguished lateral to the stomodeum, and ______ can be distinguished caudal to this structure.

Maxillary prominences, mandibular prominences

FACE The ______, formed by proliferation of mesenchyme ventral to the brain vesicles, constitutes the upper border of the ______.

frontonasal prominence, stomodeum

FACE On both sides of the frontonasal prominence, local thickenings of the surface ectoderm, the ______, originate under inductive influence of the ventral portion of the forebrain.

nasal (olfactory) placodes

FACE During the ______ week, the nasal placodes invaginate to form ______. In so doing, they create a ridge of tissue that surrounds each pit and forms the ______. The prominences on the outer edge of the pits are the ______; those on the inner edge are the ______.

fifth, nasal pits, nasal prominences, lateral nasal prominences, medial nasal prominences

FACE During the following ______ weeks, the maxillary prominences continue to increase in ______. Simultaneously, they grow ______, compressing the ______ toward the midline.

2, size, medially, medial nasal prominences

FACE Subsequently, the cleft between the ______ and the ______ is lost, and the two fuse. Hence, the upper lip is formed by the two ______ and the two ______.

medial nasal prominence, maxillary prominence, medial nasal prominences, maxillary prominences

FACE The ______ do not participate in formation of the upper lip. The lower lip and jaw form from the ______ that merge across the midline.

lateral nasal prominences, mandibular prominences

FACE Initially, the maxillary and lateral nasal prominences are separated by a deep furrow, the ______. Ectoderm in the floor of this groove forms a solid ______ that detaches from the overlying ectoderm. After canalization, the cord forms the ______; its upper end widens to form the ______. Following detachment of the cord, the ______ and ______ nasal prominences merge with each other. The nasolacrimal duct then runs from the medial corner of the ______ to the inferior meatus of the ______, and the maxillary prominences enlarge to form the ______ and ______.

nasolacrimal groove, epithelial cord, nasolacrimal duct, lacrimal sac, maxillary, lateral, eye, nasal cavity, cheeks, maxillae

FACE The nose is formed from ______ facial prominences: the ______ prominence gives rise to the bridge, the merged ______ nasal prominences provide the crest and tip, and the ______ nasal prominences form the sides (alae).

five, frontonasal, medial, lateral

INTERMAXILLARY SEGMENT As a result of medial growth of the maxillary prominences, the two ______ nasal prominences merge not only at the surface but also at a deeper level. The structure formed by the two merged prominences is the ______. It is composed of (1) a ______ component, which forms the philtrum of the upper lip; (2) an ______ component, which carries the four incisor teeth; and (3) a ______ component, which forms the triangular primary palate.

medial, intermaxillary segment, labial, upper jaw, palatal

INTERMAXILLARY SEGMENT The intermaxillary segment is continuous with the ______ portion of the ______, which is formed by the ______.

rostral, nasal septum, frontal prominence

SECONDARY PALATE Although the primary palate is derived from the ______, the main part of the definitive palate is formed by two shelflike outgrowths from the ______. These outgrowths, the ______, appear in the ______ week of development and are directed obliquely downward on each side of the tongue.

intermaxillary segment, maxillary prominences, palatine shelves, sixth

SECONDARY PALATE In the ______ week, however, the palatine shelves ascend to attain a ______ position above the tongue and fuse, forming the ______.

seventh, horizontal, secondary palate

SECONDARY PALATE Anteriorly, the shelves fuse with the ______, and the ______ is the midline landmark between the primary and secondary palates. At the same time as the palatine shelves fuse, the ______ grows down and joins with the ______ aspect of the newly formed palate.

triangular primary palate, incisive foramen, nasal septum, cephalic

NASAL CAVITIES During the ______ week, the ______ deepen considerably, partly because of growth of the surrounding nasal prominences and partly because of their penetration into the underlying mesenchyme.

sixth, nasal pits

NASAL CAVITIES At first, the ______ separates the pits from the primitive oral cavity by way of the newly formed foramina, the ______. These choanae lie on each side of the ______ and immediately behind the ______.

oronasal membrane, primitive choanae, midline, primary palate

NASAL CAVITIES Later, with formation of the secondary palate and further development of the primitive nasal chambers, the ______ lie at the junction of the ______ and the ______.

definitive choanae, nasal cavity, pharynx

NASAL CAVITIES ______ develop as diverticula of the lateral nasal wall and extend into the ______, ______, ______, and ______ bones. They reach their maximum size during ______ and contribute to the definitive shape of the face.

Paranasal air sinuses, maxilla, ethmoid, frontal, sphenoid, puberty

TEETH The shape of the face is determined not only by expansion of the ______ but also by growth of the ______ and ______ to accommodate the ______.

paranasal sinuses, mandible, maxilla, teeth

TEETH Teeth themselves arise from an ______ interaction between overlying oral epithelium and underlying mesenchyme derived from ______.

epithelial—mesenchymal, neural crest cells

TEETH By the ______ week of development, the basal layer of the epithelial lining of the oral cavity forms a C-shaped structure, the ______, along the length of the upper and lower jaws. This lamina subsequently gives rise to anumber of ______, ______ in each jaw, which form the ______ of the ______ components of the teeth.

sixth, dental lamina, dental buds, 10, primordia, ectodermal

TEETH Soon, the deep surface of the buds invaginates, resulting in the ______ of tooth development. Such a cap consists of an outer layer, the ______; an inner layer, the ______; and a central core of loosely woven tissue, the ______.

cap stage, outer dental epithelium, inner dental epithelium, stellate reticulum

TEETH The mesenchyme, which originates in the ______ in the indentation, forms the ______.

neural crest, dental papilla

TEETH As the dental cap grows and the indentation deepens, the tooth takes on the appearance of a ______ (______). Mesenchyme cells of the papilla adjacent to the inner dental layer differentiate into ______, which later produce ______.

bell, bell stage, odontoblasts, dentin

TEETH With thickening of the dentin layer, odontoblasts retreat into the ______, leaving a thin cytoplasmic process (______) behind in the ______.

dental papilla, dental process, dentin

TEETH The odontoblast layer persists throughout the life of the tooth and continuously provides ______. The remaining cells of the dental papilla form the ______ of the tooth.

predentin, pulp

TEETH In the meantime, epithelial cells of the inner dental epithelium differentiate into ______ (______). These cells produce long ______ that are deposited over the ______. Furthermore, a cluster of these cells in the inner dental epithelium forms the ______ that regulates early tooth development.

ameloblasts, enamel formers, enamel prisms, dentin, enamel knot

TEETH Enamel is first laid down at the ______ of the tooth and from here spreads toward the ______. When the enamel thickens, the ______ retreat into the ______. Here they regress, temporarily leaving a thin membrane (______) on the surface of the enamel. After ______ of the tooth, this membrane gradually sloughs off.

apex, neck, ameloblasts, stellate reticulum, dental cuticle, eruption

TEETH Formation of the root of the tooth begins when the dental epithelial layers penetrate into the underlying ______ and form the ______. Cells of the ______ lay down a layer of dentin continuous with that of the crown. As more and more ______ is deposited, the pulp chamber ______ and finally forms a canal containing ______ and ______ of the tooth.

mesenchyme, epithelial root sheath, dental papilla, dentin, narrows, blood vessels, nerves

TEETH Mesenchymal cells on the outside of the tooth and in contact with dentin of the root differentiate into ______. These cells produce a thin layer of specialized bone, the ______.

cementoblasts, cementum

TEETH Outside of the cement layer, mesenchyme gives rise to the ______, which holds the tooth firmly in position and functions as a shock absorber.

periodontal ligament

TEETH With further lengthening of the root, the ______ is gradually pushed through the overlying tissue layers into the oral cavity. The eruption of deciduous or milk teeth occurs ______ to ______ months after birth.

crown, 6, 24

TEETH Buds for the permanent teeth, which lie on the ______ aspect of the milk teeth, are formed during the ______ month of development. These buds remain dormant until approximately the ______ year of postnatal life. Then they begin to grow, pushing against the underside of the milk teeth and aiding in the shedding of them. As a permanent tooth grows, the root of the overlying deciduous tooth is resorbed by ______.

lingual, third, sixth, osteoclasts

Clinical Correlates Facial Clefts ______ and ______ are common defects that result in abnormal facial appearance and difficulties with speech.

Cleft lip, cleft palate

Clinical Correlates Facial Clefts The ______ is considered the dividing landmark between anterior and posterior cleft deformities.

incisive foramen

Clinical Correlates Facial Clefts Those anterior to the incisive foramen include ______, ______, and cleft between the ______ and ______ palates. Such defects are due to a partial or complete lack of fusion of the ______ with the ______ on one or both sides.

lateral cleft lip, cleft upper jaw, primary, secondary, maxillary prominence, medial nasal prominence

Clinical Correlates Facial Clefts Those that lie posterior to the incisive foramen include ______ and ______.

cleft [secondary] palate, cleft uvula

Clinical Correlates Facial Clefts ______ results from a lack of fusion of the palatine shelves, which may be due to smallness of the shelves, failure of the shelves to elevate, inhibition of the fusion process itself, or failure of the tongue to drop from between the shelves because of micrognathia.

Cleft palate

Clinical Correlates Facial Clefts The third category is formed by a combination of clefts lying anterior as well as posterior to the incisive foramen. Anterior clefts vary in severity from a barely visible defect in the vermilion of the ______ to extension into the ______. In severe cases, the cleft extends to a deeper level, forming a cleft of the ______, and the maxilla is split between the ______ and the ______ tooth. Frequently, such a cleft extends to the ______. Likewise, posterior clefts vary in severity from clefting of the entire ______ to clefting of the ______ only.

lip, nose, upperjaw, lateral incisor, canine, incisive foramen, secondary palate, uvula

Clinical Correlates Facial Clefts ______ is the most common syndrome associated with cleft lip with or without cleft palate. The syndrome is inherited as an autosomal dominant and is due to mutations in INTERFERON REGULATORY FACTOR 6 [IRF6; 1p32—41] that is expressed in the medial [fusing] edge of the palatal shelves. Interestingly, 88% of affected infants will have pits in their lower lip, and in 64% of these individuals, this will be the only abnormality.

Van der Woude syndrome

Clinical Correlates Facial Clefts ______ are produced by failure of the maxillary prominence to merge with its corresponding lateral nasal prominence along the line of the nasolacrimal groove. When this occurs, the nasolacrimal duct is usually exposed to the surface.

Oblique facial clefts

Clinical Correlates Facial Clefts ______, a rare abnormality, is caused by incomplete merging of the two medial nasal prominences in the midline.

Median [midline] cleft lip

Clinical Correlates Facial Clefts Infants with midline clefts are often ______ and may have ______ abnormalities that include varying degrees of loss of midline structures. Loss of midline tissue may be so extensive that the lateral ventricles fuse [______]. These defects are induced very early in development, at the beginning of ______ [days ______ to ______] when the midline of the ______ is being established.

cognitively impaired, brain, holoprosencephaly, neurulation, 19, 21, forebrain

Clinical Correlates Facial Clefts Most cases of cleft lip with or without cleft palate are multifactorial. These conditions are usually classified as [l] ______ with or without ______ and [2] ______ are thought to be etiologically and pathogenetically distinct.

cleft lip, cleft palate, cleft palate

Clinical Correlates Facial Clefts Cleft lip with or without cleft palate [approximately 1/700 births] occurs more frequently in ______ [65%] than in ______, and its incidence varies among populations. ______ and ______ have some of the highest rates [3.5/1,000], whereas ______ have the lowest [1/1,000].

males, females, Asians, Native Americans, African Americans

Clinical Correlates Facial Clefts The frequency of isolated ______ is lower than that of ______ [1/1,500 births], occurs more often in ______ [55%] than in ______. In females, the palatal shelves fuse approximately ______ week later than in males, which may be related to why isolated cleft palate occurs more frequently in females than in males.

cleft palate, cleft lip, females, males, 1

Clinical Correlates Facial Clefts Causes of cleft lip with or without cleft palate are not well defined. Some cases are syndromic and associated with certain syndromes and genes. Others are nonsyndromic but associated with some of the same genes that cause syndromes, such as ______ [van der Woude syndrome] and ______. Still, other cases are caused by exposure to ______ compounds, such as anticonvulsant medications, particularly valproic acid. Cigarette smoking during pregnancy also increases the risk for having a baby with orofacial clefts.

IRF6, MSX1, teratogenic

MOLECULAR REGULATION OF TOOTH DEVELOPMENT Teeth are present only in ______ and parallel the evolutionary appearance of the ______. Tooth development represents a classic example of an ______ interaction, in this case, between the overlying epithelium and underlying neural crest—derived mesenchyme.

vertebrates, neural crest, epithelial—mesenchymal

MOLECULAR REGULATION OF TOOTH DEVELOPMENT Regulation of tooth patterning from incisors to molars is generated by a combinatorial expression of ______ genes expressed in the mesenchyme. With respect to each tooth’s individual development, the epithelium governs differentiation to the ______, at which time this regulatory function is transferred to the ______.

HOX, bud stage, mesenchyme

MOLECULAR REGULATION OF TOOTH DEVELOPMENT Signals for development involve growth factors including ______, ______, and ______; the secreted factor ______;and transcription factors, such as ______ and ______, that interact in a complex pathway to produce cell differentiation and patterning for each tooth.

WNTs, BMPs, FGFs, SHH, MSX1, MSX2

MOLECULAR REGULATION OF TOOTH DEVELOPMENT Teeth also appear to have a signaling center that represents the “organizer” for tooth development much like the activity of the node during ______. This organizer region is called the ______, and it appears in a circumscribed region of the dental epithelium at the tips of the ______. It then enlarges at the ______ into a tightly packed group of cells but undergoes ______ (cell death) and disappears by the end of this stage. While it is present, it expresses ______, ______, and ______ and ______. ______ may regulate outgrowth of cusps much as it participates in limb outgrowth produced by the apical ectodermal ridge, whereas ______ may regulate the timing of apoptosis in knot cells.

gastrulation, enamel knot, tooth buds, cap stage, apoptosis, FGF4, SHH, BMP2, 4, FGF4, BMP4