Neural crest and the patterning of vertebrate craniofacial muscles.

Patterning of craniofacial muscles overtly begins with the activation of lineage-specific markers at precise, evolutionarily conserved locations within prechordal, lateral, and both unsegmented and somitic paraxial mesoderm populations. Although these initial programming events occur without influence of neural crest cells, the subsequent movements and differentiation stages of most head muscles are neural crest-dependent. Incorporating both descriptive and experimental studies, this review examines each stage of myogenesis up through the formation of attachments to their skeletal partners. We present the similarities among developing muscle groups, including comparisons with trunk myogenesis, but emphasize the morphogenetic processes that are unique to each group and sometimes subsets of muscles within a group. These groups include branchial (pharyngeal) arches, which encompass both those with clear homologues in all vertebrate classes and those unique to one, for example, mammalian facial muscles, and also extraocular, laryngeal, tongue, and neck muscles. The presence of several distinct processes underlying neural crest:myoblast/myocyte interactions and behaviors is not surprising, given the wide range of both quantitative and qualitative variations in craniofacial muscle organization achieved during vertebrate evolution.

Divergent and conserved roles of Dll1 signaling in development of craniofacial and trunk muscle.

Craniofacial and trunk skeletal muscles are evolutionarily distinct and derive from cranial and somitic mesoderm, respectively. Different regulatory hierarchies act upstream of myogenic regulatory factors in cranial and somitic mesoderm, but the same core regulatory network - MyoD, Myf5 and Mrf4 - executes the myogenic differentiation program. Notch signaling controls self-renewal of myogenic progenitors as well as satellite cell homing during formation of trunk muscle, but its role in craniofacial muscles has been little investigated. We show here that the pool of myogenic progenitor cells in craniofacial muscle of Dll1(LacZ/Ki) mutant mice is depleted in early fetal development, which is accompanied by a major deficit in muscle growth. At the expense of progenitor cells, supernumerary differentiating myoblasts appear transiently and these express MyoD. The progenitor pool in craniofacial muscle of Dll1(LacZ/Ki) mutants is largely rescued by an additional mutation of MyoD. We conclude from this that Notch exerts its decisive role in craniofacial myogenesis by repression of MyoD. This function is similar to the one previously observed in trunk myogenesis, and is thus conserved in cranial and trunk muscle. However, in cranial mesoderm-derived progenitors, Notch signaling is not required for Pax7 expression and impinges little on the homing of satellite cells. Thus, Dll1 functions in satellite cell homing and Pax7 expression diverge in cranial- and somite-derived muscle.

Anatomy research of nasolabial muscle structure in fetus with cleft lip: an iodine staining technique based on microcomputed tomography.

A thorough knowledge of the anatomic structure of the orbicularis oris of the upper lip and the nasalis in fetus with cleft lip is the key for the success of cleft lip repair. To understand the anatomic structure of the muscles of nasolabial region in fetus with cleft lip, the nasolabial tissues in 4 aborted fetuses with cleft lip were soaked for 7 days with iodine solution (Lugol solution of 3.75%) and were given micro-computed tomography. After the iodine solution permeated into the soft tissues, a good contrast was showed between muscle fibers and other fibrillar connective tissues. Through the observation of the obtained images, we found that most orbicularis oris fibers gathered into bundles with clear outline and only had slight deformation and displacement on the health side of the cleft of the unilateral incomplete cleft lip; however, in the lateral cleft, the muscle fibers not only had deformation and displacement but also were immature, disorganized, and not gathered into bundles. After being restored in Digital Imaging and Communications in Medicine format, the obtained images were then transferred into Materialise's interactive medical image control system, edited, and reconstructed into three-dimensional models. The models clearly showed the spatial relationship between the muscular tissues of the nasolabial region and the nasolabial outline in fetus with cleft lip.

Development of the platysma muscle and the superficial musculoaponeurotic system (human specimens at 8-17 weeks of development).

There is controversy regarding the description of the different regions of the face of the superficial musculoaponeurotic system (SMAS) and its relationship with the superficial mimetic muscles. The purpose of this study is to analyze the development of the platysma muscle and the SMAS in human specimens at 8-17 weeks of development using an optical microscope. Furthermore, we propose to study the relationship of the anlage of the SMAS and the neighbouring superficial mimetic muscles. The facial musculature derives from the mesenchyme of the second arch and migrates towards the different regions of the face while forming premuscular laminae. During the 8th week of development, the cervical, infraorbital, mandibular, and temporal laminae are observed to be on the same plane. The platysma muscle derives from the cervical lamina and its mandibular extension enclosing the lower part of the parotid region and the cheek, while the SMAS derives from the upper region. During the period of development analyzed in this study, we have observed no continuity between the anlage of the SMAS and that of the superficial layer of the temporal fascia and the zygomaticus major muscle. Nor have we observed any structure similar to the SMAS in the labial region.

Core issues in craniofacial myogenesis.

Branchiomeric craniofacial muscles control feeding, breathing and facial expression. These muscles differ on multiple counts from all other skeletal muscles and originate in a progenitor cell population in pharyngeal mesoderm characterized by a common genetic program with an adjacent population of cardiac progenitor cells, the second heart field, that gives rise to much of the heart. The transcription factors and signaling molecules that trigger the myogenic program at sites of branchiomeric muscle formation are correspondingly distinct from those in somite-derived muscle progenitor cells. Here new insights into the regulatory hierarchies controlling branchiomeric myogenesis are discussed. Differences in embryological origin are reflected in the lineage, transcriptional program and proliferative and differentiation properties of branchiomeric muscle satellite cells. These recent findings have important implications for our understanding of the diverse myogenic strategies operative both in the embryo and adult and are of direct biomedical relevance to deciphering the mechanisms underlying the cause and progression of muscle restricted myopathies.

The transcription factor Six1a plays an essential role in the craniofacial myogenesis of zebrafish.

Transcription factor Six1a plays important roles in morphogenesis, organogenesis, and cell differentiation. However, the role of Six1a during zebrafish cranial muscle development is still unclear. Here, we demonstrated that Six1a was required for sternohyoideus, medial rectus, inferior rectus, and all pharyngeal arch muscle development. Although Six1a was also necessary for myod and myogenin expression in head muscles, it did not affect myf5 expression in cranial muscles that originate from head mesoderm. Overexpression of myod enabled embryos to rescue all the defects in cranial muscles induced by injection of six1a-morpholino (MO), suggesting that myod is directly downstream of six1a in controlling craniofacial myogenesis. However, overexpression of six1a was unable to rescue arch muscle defects in the tbx1- and myf5-morphants, suggesting that six1a is only involved in myogenic maintenance, not its initiation, during arch muscle myogenesis. Although the craniofacial muscle defects caused by pax3-MO phenocopied those induced by six1a-MO, injection of six1a, myod or myf5 mRNA did not rescue the cranial muscle defects in pax3 morphants, suggesting that six1a and pax3 do not function in the same regulatory network. Therefore, we proposed four putative regulatory pathways to understand how six1a distinctly interacts with either myf5 or myod during zebrafish craniofacial muscle development.

Heart and craniofacial muscle development: a new developmental theme of distinct myogenic fields.

Head muscle development has been studied less intensively than myogenesis in the trunk, although this situation is gradually changing, as embryological and genetic insights accumulate. This review focuses on novel studies of the origins, composition and evolution of distinct craniofacial muscles. Cellular and molecular parallels are drawn between cardiac and branchiomeric muscle developmental programs, both of which utilize multiple lineages with distinct developmental histories, and argue for the tissues' common evolutionary origin. In addition, there is increasing evidence that the specification of skeletal muscles in the head appears to be distinct from that operating in the trunk: considerable variation among the different craniofacial muscle groups is seen, in a manner resembling myogenic specification in lower organisms.

Developmental origins of species-specific muscle pattern.

Vertebrate jaw muscle anatomy is conspicuously diverse but developmental processes that generate such variation remain relatively obscure. To identify mechanisms that produce species-specific jaw muscle pattern we conducted transplant experiments using Japanese quail and White Pekin duck, which exhibit considerably different jaw morphologies in association with their particular modes of feeding. Previous work indicates that cranial muscle formation requires interactions with adjacent skeletal and muscular connective tissues, which arise from neural crest mesenchyme. We transplanted neural crest mesenchyme from quail to duck embryos, to test if quail donor-derived skeletal and muscular connective tissues could confer species-specific identity to duck host jaw muscles. Our results show that duck host jaw muscles acquire quail-like shape and attachment sites due to the presence of quail donor neural crest-derived skeletal and muscular connective tissues. Further, we find that these species-specific transformations are preceded by spatiotemporal changes in expression of genes within skeletal and muscular connective tissues including Sox9, Runx2, Scx, and Tcf4, but not by alterations to histogenic or molecular programs underlying muscle differentiation or specification. Thus, neural crest mesenchyme plays an essential role in generating species-specific jaw muscle pattern and in promoting structural and functional integration of the musculoskeletal system during evolution.

The facial expression musculature in primates and its evolutionary significance.

Facial expression is a mode of close-proximity non-vocal communication used by primates and is produced by mimetic/facial musculature. Arguably, primates make the most-intricate facial displays and have some of the most-complex facial musculature of all mammals. Most of the earlier ideas of primate mimetic musculature, involving its function in facial displays and its evolution, were essentially linear "scala natural" models of increasing complexity. More-recent work has challenged these ideas, suggesting that ecological factors and social systems have played a much larger role in explaining the diversity of structures than previously believed. The present review synthesizes the evidence from gross muscular, microanatomical, behavioral and neurobiological studies in order to provide a preliminary analysis of the factors responsible for the evolution of primate facial musculature with comparisons to general mammals. In addition, the unique structure, function and evolution of human mimetic musculature are discussed, along with the potential influential roles of human speech and eye gaze.

Importance of muscle movement for normal craniofacial development.

After the craniofacial structures have completed embryologic development, movement of facial muscles begins. Paraxial mesoderm of the first (mastication) and second pharyngeal (facial expression) arches gives rise to the muscles of the craniofacial area. Muscles derived from the third and fourth pharyngeal arches are involved in swallowing and vocalization. For the human newborn face to have a normal morphologic appearance, contractions of these muscles must occur to stimulate forward growth of bone, cartilage growth, and facial muscle bulk. Facial muscles begin to contract between 6 and 8 weeks of embryonic development and can be observed on prenatal ultrasound by 9 weeks after fertilization. Lack of craniofacial muscle contractions may lead to ocular hypertelorism, flat zygoma and midface, high bridge of the nose, depressed tip of the nose, small and open mouth, trismus, microretrognathia, small tongue, and abnormal palate (high arch, bifid uvula, submucous cleft, and cleft palate).

[Age dynamics of the human maxillofacial apparatus development in the early period of prenatal ontogenesis].

The literature review discusses the debatable problems on terms of separation of different anlages of human maxillo-facial apparatus, chronology of histo- and organogenetic remodeling of hard and soft tissues during the period of their formation in the first trimester of pregnancy. It is suggested that these controversies are most likely determined by imperfection of current embryogenesis periodization systems and of criteria of human embryos and fetuses age definition; therefore further research in this direction is required.

Etv1 Controls the Establishment of Non-overlapping Motor Innervation of Neighboring Facial Muscles during Development.

The somatotopic motor-neuron projections onto their cognate target muscles are essential for coordinated movement, but how that occurs for facial motor circuits, which have critical roles in respiratory and interactive behaviors, is poorly understood. We report extensive molecular heterogeneity in developing facial motor neurons in the mouse and identify markers of subnuclei and the motor pools innervating specific facial muscles. Facial subnuclei differentiate during migration to the ventral hindbrain, where neurons with progressively later birth dates-and evolutionarily more recent functions-settle in more-lateral positions. One subpopulation marker, ETV1, determines both positional and target muscle identity for neurons of the dorsolateral (DL) subnucleus. In Etv1 mutants, many markers of DL differentiation are lost, and individual motor pools project indifferently to their own and neighboring muscle targets. The resulting aberrant activation patterns are reminiscent of the facial synkinesis observed in humans after facial nerve injury.

Morphometric aspects of the facial and skeletal muscles in fetuses.

OBJECTIVES: There are few research reports providing a comparison of the muscle fiber morphometry between human fetuses and adults. Data on fetal and adult muscle fibers would be valuable in understanding muscle development and a variety of muscle diseases. This study investigated human muscle fiber growth to clarify the difference between the facial muscles and other skeletal muscles. METHODS: The materials were obtained from three male fetuses (6-month-old) and 11 Japanese male cadavers aged 43-86 years (average: 71.8). Human buccinator muscles (facial muscles), masseter and biceps brachii muscles (skeletal muscles) were resected. We counted the muscle fibers and measured their transverse area. We also calculated the number of muscle fibers per mm(2) (NMF) and the average transverse area of the muscle fibers (TAMFs). RESULTS: The average of the NMF of the buccinator, masseter and biceps brachii muscles in fetuses had, respectively, 19, 37, and 22 times as many fibers as those in adults. The average fetus/adult ratios of the TAMF of the buccinator, masseter and biceps brachii muscles were 4.0%, 2.4%, 4.1%, respectively. CONCLUSIONS: The average NMF for all kinds of muscles decreased after birth; however, the peak in life-span or decreases with the aging process tended to vary with the kind of muscles examined. The average TAMF for all kinds of muscles enlarged after birth. We considered that the enlargement of the TAMF was connected with the emergence of fetal movements and functional demands after birth.

Absence of the lateral philtral ridges: a clue to the structural basis of the philtrum.

This study compares philtral development in the normal fetus with philtral development in specimens lacking normal philtral landmarks. Distinct differences in the structure of the upper lip were discovered between the two groups using a histological comparison. A new mechanism for the structural basis of the philtrum is proposed on the basis of these differences.

Development of craniofacial musculature in Monodelphis domestica (Marsupialia, Didelphidae).

Development of craniofacial muscles of Monodelphis domestica (Marsupialia, Didelphidae) is described. In a period of 4-6 days all craniofacial muscles in M. domestica progress from myoblast condensation, to striated myofibers that are aligned in the direction of adult muscles and possess multiple, lateral nuclei. This process begins 1 to 2 days before birth and continues during the first few days after birth. Compared to other aspects of cranial development, muscle development in M. domestica is rapid. This rapid and more or less simultaneous emergence of craniofacial muscles differs from the previously described pattern of development of the cranial skeleton in marsupials, which displays a mosaic of acceleration and deceleration of regions and individual elements. Unlike the skeletal system, craniofacial muscles show no evidence of regional specialization during development. M. domestica resembles eutherian mammals in the relatively rapid and more or less simultaneous differentiation of all craniofacial muscles. It differs from eutherian taxa in that most stages of myogenesis occur postnatally, following the onset of function. The timing of the development of muscular and skeletal structures is compared and it is concluded that the relatively early development of muscle is not reflected by any particular acceleration of the differentiation or growth of skeletal structures. Finally, the difficulties in accounting for complex internal arrangements of muscles such as the tongue, given current models of myogenesis are summarized.

The development of facial muscles and nerves in relation to the Möbius syndrome.

This paper discusses descriptive and experimental embryologic material that may be of relevance in understanding the pathologic findings of, and attempting treatment of, congenital facial paralysis. The embryology of the human facial nerves and muscles is described. In experimental animals muscles undergo early stages of morphogenesis and differentiation in the absence of nerves and then undergo gradual atrophy. In th absence of muscle fibers, the bulk of embryonic motor nerves that would normally innervate the muscle die.

Development of the orbicularis oris muscle in normal and cleft lip and palate human fetuses using three-dimensional computer reconstruction.

As part of an ongoing study of cleft lip and palate fetal morphology, normal and dysmorphic development of the human fetal orbicularis oris muscle was studied in a cross-sectional sample of 29 human fetuses (20 "normal" and 9 cleft lip and palate) ranging in age from 8 to 21 postmenstrual weeks. The specimens were embedded in celloidin and sectioned at 20 microns, and every tenth section was stained with hematoxylin and eosin. A computer reconstruction technique was applied to produce three-dimensional representations of the orbicularis oris muscle. The orbicularis oris muscle in the normal fetal sample with discernible lip fibers (N = 15) increased symmetrically in both fiber density and complexity from 12 to 21 weeks. Metrically, muscle volume and thickness growth curves were consistent with qualitative observations. In contrast, the unilateral cleft lip and palate fetal specimens with discernible lip fibers (N = 3) exhibited a 3.5-week delay in overall muscle development, asymmetrical fiber distribution, and abnormal fiber insertions. However, quantitatively, no significant (p greater than 0.05) differences were noted in orbicularis oris muscle thickness or volume between the normal and cleft lip and palate fetal specimens through 21 weeks. Findings suggest that orbicularis muscle deficiency, noted clinically in cleft lip and palate neonates, may be a result of perinatal functional dysmorphogenesis rather than congenital mesenchymal reduction or deficiency.

Does a superficial musculoaponeurotic system exist in the face and neck? An anatomical study by the tissue plastination technique.

An exact knowledge of the subcutaneous layers in the different regions of the face and neck is important in several surgical disciplines. In the parotid region, a superficial musculoaponeurotic system (SMAS) has been described. The existence of a SMAS as a guiding structure for the surgeon in the other regions of the face and neck has been discussed but is controversial. Therefore, the authors investigated the development of the subcutaneous connective-tissue layers in the different facial regions and in the neck. They studied these regions in 22 human fetuses using the technique of plastination histology and in three newborn and three adult specimens using sheet plastination. In addition, they dissected the neck and face in 10 fresh adult cadavers to identify the SMAS as in the surgical situation. The results show that no SMAS could be detected in any facial regions other than the parotid region. In the parotid region, it is thick and attached to the parotid sheath. However, it becomes very thin, discontinuous, and undissectable in the cheek area. No SMAS can be found in the neck, in which the authors are the first to describe a fascia covering both sides of the platysma. This fascia has close topographical connections to the subcutaneous layers of the adjoining regions. On the basis of these findings, the surgical pathways have to be defined regionally in the face. A "platysma fascia" can be considered as a surgical landmark in the neck. Therefore, the authors conclude that it is not justified to generalize a SMAS as a surgical guiding structure.

Development of the submandibular gland and its closer neighboring structures in human embryos and fetuses of 19-67 mm CRL.

The fetal development and arrangement of the human submandibular gland was studied by means of serial sections of human embryos and fetuses ranging from 19 mm to 67 mm CRL. Computer assisted 3-dimensional reconstruction leads to the following observations: 1. The orifice of the submandibular duct is located in the medial paralingual sulcus. 2. There is evidence that the extension and location of WHARTON's duct is influenced by the surrounding structures. 3. The surface of the submandibular gland primordium shows impressions of the neighboring structures. 4. The glandular tissue is encapsulated in condensed mesenchyme.

The buccinator muscle: an original morphogenetical study.

The buccinator muscle, a cutaneous muscle derived from the second arc, is innervated by the facial nerve. It is made of 3 bundles extended into the cheek, from the pterygo-mandibular ligament to the modiolus. It is used for diverse buccal functions. This study attempts to give a better insight of the embryogenesis and the development of the muscle. After taking samples by microdissection under binocular microscope, of this region of embryos and foeti, we performed histological sections. They were then coloured by Masson's trichome for their observation under photon microscopy. From seventieth week we observed the presence of a peri-mucous mesenchyma between the cartilaginous condensation of the "pre premier arc" and Meckel's cartilage. The buccinator presents an insertion on the modiolus, sliding under the latter it runs forwards, it is at the origin of the formation of the orbicularis internus of the lips (musculus orbicularis oris). This muscle displaces its posterior insertion downwards, with the development of the face in the child and the adolescent, notably with the modification in vertical dimension due to the arrival of the deciduous teeth before the permanent dentition. Furthermore it appears that buccinator does not play a role as a sphincter in the secretion of the parotid glands.