Molecular and cellular changes associated with the evolution of novel jaw muscles in parrots.

Vertebrates have achieved great evolutionary success due in large part to the anatomical diversification of their jaw complex, which allows them to inhabit almost every ecological niche. While many studies have focused on mechanisms that pattern the jaw skeleton, much remains to be understood about the origins of novelty and diversity in the closely associated musculature. To address this issue, we focused on parrots, which have acquired two anatomically unique jaw muscles: the ethmomandibular and the pseudomasseter. In parrot embryos, we observe distinct and highly derived expression patterns for Scx, Bmp4, Tgfß2 and Six2 in neural crest-derived mesenchyme destined to form jaw muscle connective tissues. Furthermore, immunohistochemical analysis reveals that cell proliferation is more active in the cells within the jaw muscle than in surrounding connective tissue cells. This biased and differentially regulated mode of cell proliferation in cranial musculoskeletal tissues may allow these unusual jaw muscles to extend towards their new attachment sites. We conclude that the alteration of neural crest-derived connective tissue distribution during development may underlie the spatial changes in jaw musculoskeletal architecture found only in parrots. Thus, parrots provide valuable insights into molecular and cellular mechanisms that may generate evolutionary novelties with functionally adaptive significance.

Masticatory muscle defects in hemifacial microsomia: a new embryological concept.

First arch syndromes correspond to a wide spectrum of human latero-facial congenital anomalies affecting cranial neural crest cells (CNCCs) derivatives of the first pharyngeal arch (PA1). The abnormal traits display variable quantitative expression and are often unilateral. Mandibular skeletal defects are invariably accompanied by hypoplasia or agenesis of masticatory muscles, but no explanation has been proposed for this association. Indeed, during embryonic development, CNCCs give only rise to skeletal components of the head while muscles derive from cephalic myogenic mesodermal cells (CMMCs). Recent studies on animal models have shown that communication between CNCCs and CMMCs is essential for the development of masticatory muscles: genetic lesions affecting only CNCCs can prevent muscularization of the jaws. To evaluate the involvement of CNCC/CMMC interactions in human craniofacial development, we performed a quantitative analysis of masticatory muscle and mandibular bone volumes on craniofacial CT-scans from 8 children, ages 3 months to 16 years, affected by hemifacial microsomia. We found that: (1) in seven patients the masseter muscle is absent in the affected side; (2) the absence of masseter is correlated neither with the age of the patients nor with the volume and shape of the affected ramus; and (3) in all cases the pterygoid and the temporal muscles are either reduced or absent. Our findings suggest that an early developmental event is the origin of the muscular defects in these patients. We propose that the hypoplasia or agenesis of masticatory muscles derives from a defect in the CNCCs/CMMCs communication during early embryonic development.

Muscle development: forming the head and trunk muscles.

The morphological events forming the body's musculature are sensitive to genetic and environmental perturbations with high incidence of congenital myopathies, muscular dystrophies and degenerations. Pattern formation generates branching series of states in the genetic regulatory network. Different states of the network specify pre-myogenic progenitor cells in the head and trunk. These progenitors reveal their myogenic nature by the subsequent onset of expression of the master switch gene MyoD and/or Myf5. Once initiated, the myogenic progression that ultimately forms mature muscle appears to be quite similar in head and trunk skeletal muscle. Several genes that are essential in specifying pre-myogenic progenitors in the trunk are known. Pax3, Lbx1, and a number of other homeobox transcription factors are essential in specifying pre-myogenic progenitors in the dermomyotome, from which the epaxial and hypaxial myoblasts, which express myogenic regulatory factors (MRFs), emerge. The proteins involved in specifying pre-myogenic progenitors in the head are just beginning to be discovered and appear to be distinct from those in the trunk. The homeobox gene Pitx2, the T-box gene Tbx1, and the bHLH genes Tcf21 and Msc encode transcription factors that play roles in specifying progenitor cells that will give rise to branchiomeric muscles of the head. Pitx2 is expressed well before the onset of myogenic progression in the first branchial arch (BA) mesodermal core and is essential for the formation of first BA derived muscle groups. Anterior-posterior patterning events that occur during gastrulation appear to initiate the Pitx2 expression domain in the cephalic and BA mesoderm. Pitx2 therefore contributes to the establishment of network states, or kernels, that specify pre-myogenic progenitors for extraocular and mastication muscles. A detailed understanding of the molecular mechanisms that regulate head muscle specification and formation provides the foundation for understanding congenital myopathies. Current technology and mouse model systems help to elucidate the molecular basis on etiology and repair of muscular degenerative diseases.

Skeletal units of the human embryonic mandible.

The development of the mandible was traced on serial sections of 20 human embryos aged 5-8 weeks (developmental stages 13-23). Special consideration was given to the differentiation of skeletal units proposed by Sperber. The first skeletal units, namely the mandibular body, the alveolar unit and the condylar unit, may be distinguished in the 7(th) week. The primordia of all units are identified by the end of the embryonic period (8 weeks).

The development of mastication in rodents: from neurons to behaviors.

The development of suckling behavior is a fundamental characteristic of mammalian development. The occurrence of this behavior across mammals allows us to extrapolate information from animal models to better understand normal and abnormal masticatory development in infants. This review focuses on prenatal cell, molecular, and morphological changes in rat and/or mouse masticatory muscles, trigeminal motoneurons (Mo5) and mesencephalic trigeminal neurons (Me5) that accompany the development of suckling behavior. A special emphasis is placed on N-methyl-d-aspartate (NMDA) receptor subunit expression because of the important role that NMDA receptors play in the production of rhythmical jaw movements and neuronal development. Prenatally the timing of NMDA subunit changes follows neuromuscular junction formation in masticatory muscles, and is coincident with the emergence of rhythmical jaw movements and in vitro rhythmical trigeminal activity. Our data suggest that NMDA receptor subunit changes in Mo5 and Me5 are synchronized with the emergence of rhythmical jaw movements and trigeminal motor activity.

[Musculoskeletal connections. Study of two cases of oto-mandibular dysplasia]. / Connexions musculo-squelettiques. Etude de deux cas de dysplasies oto-mandibulaires.

The current genetic data stress the importance of musculo-skeletal connections in the development of a coherent system connecting the tendons and aponeurosis muscles with the osseous parts. The observations in tomodensitometry of musculo-skeletal connections in otomandibular dysostosis make it possible qualitatively to observe the development of the muscles and their functions.

Embryonic and postnatal development of masticatory and tongue muscles.

This review summarizes findings concerning the unique developmental characteristics of mouse head muscles (mainly the masticatory and tongue muscles) and compares their characteristics with those of other muscles. The developmental origin of the masticatory muscles is the somitomeres, whereas the tongue and other muscles, such as the trunk (deep muscles of the back, body wall muscles) and limb muscles, originate from the somites. The program controlling the early stages of masticatory myogenesis, such as the specification and migration of muscle progenitor cells, is distinctly different from those in trunk and limb myogenesis. Tongue myogenesis follows a similar regulatory program to that for limb myogenesis. Myogenesis and synaptogenesis in the masticatory muscles are delayed in comparison with other muscles and are not complete even at birth, whereas the development of tongue muscles proceeds faster than those of other muscles and ends at around birth. The regulatory programs for masticatory and tongue myogenesis seem to depend on the developmental origins of the muscles, i.e., the origin being either a somite or somitomere, whereas myogenesis and synaptogenesis seem to progress to serve the functional requirements of the masticatory and tongue muscles.

[Ontogeny of the jaw].

Four pairs of branchial arch appear apparently in the neck region of human embryo about 32 days after fertilization. Maxillary prominence of the first branchial arch gives rise to the maxilla and zygomatic bone etc., and mandibular prominence forms the mandible and so on. Muscles for mastication are also derived from 1st branchial arch, into which fifth cranial nerves grow from the brain. Thus, human embryo improves the 1st branchial arches into the upper and lower jaws, and forms digestive organs needed for intake, mastication, and swallowing of foods. Finally they develop the brain for integral treatment of sensory information from eyes, tongue, nose, and ears.

Morphogenesis of parrot jaw muscles: understanding the development of an evolutionary novelty.

Parrots have developed novel head structures in their evolutionary history. The appearance of two new muscles for strong jaw adduction is especially fascinating in developmental and evolutionary contexts. However, jaw muscle development of parrots has not been described, despite its uniqueness. This report first presents the normal developmental stages of the cockatiel (Nymphicus hollandicus), comparable to that of the chick. Next, the peculiar skeletal myogenesis in the first visceral arch of parrots is described, mainly focusing on the development of two new jaw muscles. One of the parrot-specific muscles, M. ethmomandibularis, was initially detected at Nymphicus Stage 28 (N28) as the rostral budding of M. pterygoideus. After N32, the muscle significantly elongates rostrodorsally toward the interorbital septum, following a course lateral to the palatine bone. Another parrot-specific muscle, M. pseudomasseter, was first recognized at N36. The muscle branches off from the posteromedial M. adductor mandibulae externus and grows in a dorsolateral direction, almost covering the lateral surface of the jugal bar. The upper tip of the muscle is accompanied by condensed mesenchyme, which seems to be derived from cephalic neural crest cells.

Control of facial muscle development by MyoR and capsulin.

Members of the MyoD family of basic helix-loop-helix (bHLH) transcription factors control the formation of all skeletal muscles in vertebrates, but little is known of the molecules or mechanisms that confer unique identities to different types of skeletal muscles. MyoR and capsulin are related bHLH transcription factors expressed in specific facial muscle precursors. We show that specific facial muscles are missing in mice lacking both MyoR and capsulin, reflecting the absence of MyoD family gene expression and ablation of the corresponding myogenic lineages. These findings identify MyoR and capsulin as unique transcription factors for the development of specific head muscles.

The Krox-20 null mutation differentially affects the development of masticatory muscles.

The Krox-20 null mutation results in a loss of rhombomeres 3 and 5, which give rise to neurons that are essential to oral motor behaviors. Thus, the Krox-20 null mutant is an excellent model to investigate the development of oral motor circuitry. Our morphological examination of embryonic and neonatal Krox-20 null mutants revealed that a significant reduction of anterior digastric and mylohyoid muscles, the primary jaw openers, occurs between embryonic days 15 and 19. There are no gross morphological alterations in other masticatory muscles. These findings demonstrate that Krox-20 expression is critical for the normal development of the primary jaw opener musculature and they help explain previous studies documenting a reduction in jaw opening in Krox-20 null mutants. Since jaw opening is the power stroke of suckling behavior, our data help explain the reduction of colostrum/milk ingestion in Krox-20 null mutant neonates.

Prenatal development of the muscles in the floor of the mouth in human embryos and fetuses from 6.9 to 76 mm CRL.

The development of the muscles in the floor of the mouth is described in 10 human embryos and fetuses ranging from 6.9 to 76 mm CRL by means of computer-aided graphical 3D-reconstructions. All primordia of the muscles in the floor of the mouth could be identified from the 15.6 mm CRL stage on. The proportions and insertion lines of the early muscles were found to be different from adult anatomy. Each muscle first inserted in the medial surface of Meckels cartilage, but during the developmental period between 19 and 68 mm CRL the insertion lines were gradually transposed to the bony ridges of the mandible which progrediently embraced Meckels cartilage. The fibers of the mylohyoid muscles left the anterior region near the symphysis mentalis free during all stages of this study. The digastric muscle revealed only one belly with a constriction of its continuous fibers where it passed the hyoid bone primordium. There was no attachment of digastric muscle fibers to the hyoid; only geniohyoid and mylohyoid fibers. Geniohyoid and genioglossus muscles basically correspond to their definite arrangement, but they underwent proportional changes. Individual specimens embodied irregularities such as accessory geniohyoid and hyoid portions and muscle fibers separate from the mylohyoide muscle.

Computerized 3-dimensional study of the embryologic development of the human masticatory muscles and temporomandibular joint.

PURPOSE: In this study, the development of human embryonic temporomandibular joint (TMJ) and masticatory muscles were investigated by using computed 3-dimensional reconstructions. MATERIALS AND METHODS: Sixteen human embryos and fetuses, ranging from 6.5 to 107 mm crown-rump length, were examined. RESULTS: At 10 weeks, a band of mesenchyme extending from the attachment of the lateral pterygoid muscle to the condylar process was observed to pass through the medial side of the condylar process to attach to the malleus. The temporal, masseter, and pterygoid muscles develop from the so called "temporal muscle" primordium, and the temporal muscle was in continuity with the masseter muscle until 14 weeks of fetal life. CONCLUSIONS: The study shows that the muscles of mastication arise from a single primordium. It also confirms the presence of a ligamentous attachment between the lateral pterygoid muscle and the malleus.

Formation of a full complement of cranial proprioceptors requires multiple neurotrophins.

Inactivation of neurotrophin-3 (NT3) completely blocks the development of limb proprioceptive neurons and their end organs, the muscle spindles. We examined whether cranial proprioceptive neurons of the trigeminal mesencephalic nucleus (TMN) require NT3, brain-derived neurotrophic factor (BDNF) or neurotrophin-4 (NT4) for their development. Complements of TMN neurons and masticatory muscle spindles were decreased by 62% in NT3 null mutants, 33% in BDNF null mutants, and 10% in NT4 null mutant mice at birth. The extent of proprioceptive deficiencies differed among different masticatory muscles, particularly in NT3 null mice. Masticatory muscles of embryonic mice heterozygous for the NT3(lacZneo) or BDNF(lacZ) reporter genes expressed both NT3 and BDNF, consistent with target-derived neurotrophin support of TMN neurons. Although more than 90% of TMN neurons expressed TrkB as well as TrkC receptor proteins by immunocytochemistry in wild-type newborns, TrkC or TrkB null mice exhibited only partial proprioceptive deficiencies similar to those present in NT3 or BDNF;NT4 null mice. Thus, in terms of the survival outcome, two main subpopulations of TMN neurons may exist during embryogenesis, one dependent on TrkC/NT3 functioning and the other utilizing TrkB/BDNF signaling. The differential dependence of TMN neurons on neurotrophins may reflect differential accessibility of the neurons to limiting amounts of NT3, BDNF, or NT4 in target tissues, especially if the tissue distribution or levels of BDNF, NT3, and NT4 were dynamically regulated both spatially and temporally.

Anatomic study of complex anomalies of the digastric muscle and review of the literature.

The digastric muscles of 99 cadavers were examined bilaterally. In 5 of them, the digastric muscles showed different types of complex abnormalities. These complex anomalies should be kept in mind in functional studies involving the floor of mouth and evaluating the same structures with CT and MR imaging. Secondly, the embryological basis of the isolated anomalies of the anterior digastric muscle with respect to its occurrence together with the mylohyoid muscle stressed in this article needs further studies of their development from the first branchial arch.

Jaw muscle development as evidence for embryonic repatterning in direct-developing frogs.

The Puerto Rican direct-developing frog Eleutherodactylus coqui (Leptodactylidae) displays a novel mode of jaw muscle development for anuran amphibians. Unlike metamorphosing species, several larval-specific features never form in E. coqui; embryonic muscle primordia initially assume an abbreviated, mid-metamorphic configuration that is soon remodelled to form the adult morphology before hatching. Also lacking are both the distinct population of larval myofibres and the conspicuous, larval-to-adult myofibre turnover that are characteristic of muscle development in metamorphosing species. These modifications are part of a comprehensive alteration in embryonic cranial patterning that has accompanied life history evolution in this highly speciose lineage. Embryonic 'repatterning' in Eleutherodactylus may reflect underlying developmental mechanisms that mediate the integrated evolution of complex structures. Such mechanisms may also facilitate, in organisms with a primitively complex life cycle, the evolutionary dissociation of embryonic, larval, and adult features.

Muscle cell death during the development of head and neck muscles in the chick embryo.

Degenerating myofibers have been reported in the embryos and neonates of a number of birds and mammals, but neither the pervasiveness of the phenomenon nor the spatio-temporal patterns of degeneration has been examined in detail. Using transmission electron microscopy, we determined the patterns of muscle cell death in the chick biventer cervicis, a head extensor muscle. Cell death is most pronounced at incubation days 10 through 15, and occurs throughout the muscle. This is the period during which many myofiber clusters segregate into individual fibers, each with a separate basal lamina, and secondary myofibers become demarcated. Cells of largest diameter, presumably the primary myofibers, are preferentially affected. Degenerating cells exhibit a cohort of cytological features consistent with apoptosis, including the presence of dense, darkly-staining, hypercontracted myofibrils, misshapen nuclei with irregular chromatin condensations along the nuclear envelope, and scores of cytoplasmic vesicles and vacuoles. In cross section some large diameter muscle cells are characterized by sparse, flocculent cytoplasm that is devoid of myofibrils and organelles. Some show disintegrating cell membranes. In longitudinal section 200-300 microns long regions of hypercontracted myofibrils alternate with areas devoid of fibrils; this arrangement suggests that the myofibrils break into segments that are in register along one part of a muscle fiber and entirely absent from the adjacent length of fiber. We have observed similar patterns of muscle cell degeneration in the complexus, splenius cervicis, depressor mandibulae, and branchiomandibularis muscles. By day 18 of incubation most signs of degeneration are absent and by hatching (day 21) the muscle fibers all appear healthy. Many of these cytological changes in embryonic head muscle cells are characteristic of programmed cell death. We hypothesize that large-scale death of myocytes is a normal part of avian myogenesis and an important mechanism for affecting the transformation from embryonic to hatching muscle patterning.

Morphology and analysis of the development of the human temporomandibular joint and masticatory muscle.

The calcification levels of the mandible and the temporal bone of human fetuses, which ranged from 12 to 32 weeks of gestation, were systematically investigated with a soft X-ray analyzer linked to an image analyzer. The profile of the condylar process (head) revealed high levels of calcification, in contrast to that in the mandibular fossa of the temporal bone. The basal portion of the condylar process and the mandibular notch exhibited moderate calcification from 12 weeks of gestation. The weight and the cross-sectional areas of the muscle and the muscle fibers in masticatory muscles (masseter, temporal, medial, and lateral pterygoid muscles) are all increased gradually during development from 12 to 32 weeks of gestation. These changes in calcification and in cross-sectional area of muscle suggest that muscle development may be related to bone calcification during formation of the mandible.

Study of pterygospinosus muscle in human fetuses.

The arrangement of the pterygospinosus muscle was analyzed in 5 human fetuses. The pterygospinosus muscle extends from the posterior border of the lateral lamina of the pterygoid process to Meckel's cartilage. Such an arrangement would permit its action on the joint formed by Meckel's cartilage and the incus of the middle ear. The pterygospinosus muscle is a remnant of the masticatory muscle group. The relationships of the pterygospinosus muscle with the mandibular nerve and its branches and the maxillary artery and its branches were analyzed.

The relationships between the temporomandibular joint disc and related masticatory muscles in humans.

A study of the relationships of the temporomandibular joint disc and the lateral pterygoid, temporalis, and masseter muscles during the human fetal period and in the adult was conducted. The superior head of the lateral pterygoid muscle was seen to insert into the anteromedial two thirds of the temporomandibular joint disc. The fibers of the posterior one third of the temporalis muscle and fibers of the deep bundle of the masseter muscle were attached on the anterolateral one third of the disc. The attachment of these muscles to the disc was through the anterior extension of the disc, also known as the premeniscal or prediscal lamina. The possible functional role of these muscle attachments is discussed.