Oro-Cranio-Facial Development Prenatal

• Day of Day Conceptus

  • Week 1, days 1-7 = pre-implantation

  • Week 2, days 8 – 14 = pre-embryonic

    • after implantation
    • Formation of Bilaminar Germ Disc

  • Week 3 -8 : [embryonic periode]

    • Formation of Germ Layers and Early Tissue and Organ Differentiation: 3rd week
      • Third week: Trilaminar Embryo Develops
        • Primitive Streak Forms dorsally
        • Forms neural tube, notochord (cartilaginous rod, future spine) and neural crest cells
        • Notochord : mesoderm origin
        • Head formation
          • Occurs at the earliest stages • ~~~ brain development
          • Orofacial from CNC (ectoderm origin) • Calvaria from mesoderm (paraxial)
    • Organogenetic Period: 4th – 8th Weeks

      • Pharyngeal apparatus

        @ : 4th week

        • Very dominant, typical feature in head&neck dev; esp. lateral and ventral regions of the head and neck.

        • tdd

          • lateral plate mesoderm + ekstensi lateral dari pharyngeal endoderm + CNC migration + ectoderm

        • Inti

          jar.mesenchymal, diselubungi ectoderm di permukaan, dan lap.dalam dilapisi epithelia derivat endoderm

        • Pharyngeal arches

          • ciri

            • The pharyngeal arches contribute extensively to the formation of the face, nasal cavities, mouth, larynx, pharynx, and neck

            • @ punya arteri & saraf cranial

            • Pada manusia ada 5, karena yg ke-5 regresi

            • 1 &2 s.d midline

            • Makin caudal makin pendek

            • Dipisahkan satu sama lain oleh

              – Pharyngeal pouch [internal]

              – Pharygeal grooves [external]

            • Permukaan luar ditutupi ectoderm

            • Permukaan dalam (pharyngeal) oleh endoderm; kcl 1st arcus oleh ectoderm

            • INTI : sel Neural Crest , dg sekitarnya dikelilingi mesoderm.

            • @  diff: – Mesoderm  otot, pembuluh darah* – CNC  tulang, cartilago, jaringan ikat.

          • The dorsal end of the first pharyngeal arch cartilage :

            • Early in development, small nodules break away from the proximal part of this cartilage and form malleus and incus.
            • The middle part of the cartilage regresses, but its perichondrium forms the anterior ligament of malleus and the sphenomandibular ligament.

          • Ventral parts

            • primordial mandible
            • The cartilage → intramembranous ossification

          • The first pharyngeal arch (mandibular arch)

            • = Meckel cartilage
            • separates into two prominences
              • The maxillary prominence (MXP) gives rise to the maxilla, zygomatic bone, and a portion of the vomer .
              • The mandibular prominence (MDP) forms the mandible. The proximal mandibular prominence also forms the squamous temporal bone (os temporalis).

          • 1st arch

            Tdd processus maxillar [dorsal] & mandibular [ventral]

          • The second pharyngeal arch (hyoid arch)

            • os hyoid, (along with parts of the third and fourth arches)
            • During the 5th week, the second pharyngeal arch enlarges and overgrows the third and fourth arches, forming an ectodermal depression-the cervical sinus

          • The third pharyngeal arch cartilage,

            • greater cornu and the inferior part of the body of the hyoid bone.
            • The musculature is limited to the stylopharyngeus muscles. These muscles are innervated by the glossopharyngeal nerve, the nerve of the third arch

          • The fourth and sixth pharyngeal arch cartilages fuse

            • laryngeal cartilages, except for the epiglottis.
            • Muscles of the fourth arch (cricothyroid, levator palatini, and constrictors of the pharynx) are innervated by the superior laryngeal branch of the vagus, the nerve of the fourth arch.
            • Intrinsic muscles of the larynx are supplied by the recurrent laryngeal branch of the vagus, the nerve of the sixth arch.

        • Pharingeal grooves/cleft

          • on each side during the fourth and fifth weeks.
          • separate the pharyngeal arches externally .
          • Only one pair of grooves contributes to postnatal structures; the first pair persists as the external acoustic meatus or ear canals
          • The other grooves lie in a slitlike depression-the cervical sinus-and are normally obliterated along with the sinus as the neck.
          • [end of the 7 th week], the second to fourth pharyngeal grooves and the cervical sinus have disappeared, giving the neck a smooth contour

        • Pharyngeal pouches

          • develop in a craniocaudal sequence between the arches
          • There are 4 well-defined pairs of pharyngeal pouches; the 5th pair is rudimentary or absent.
          • The endoderm of the pouches contacts the ectoderm of the pharyngeal grooves  the double-layered pharyngeal membranes that separate the pharyngeal pouches from the pharyngeal grooves

        • Pharyngeal cyst

          • occurs when parts of the pharyngeal grooves 2, 3, and 4 that are normally obliterated persist, thereby forming a cyst.
          • It is generally found near the angle of the mandible

        • Thyroglossal duct cyst

          • occurs when parts of the thyroglossal duct persist
          • It is most commonly located in the midline near the hyoid bone, but it may also be located at the base of the tongue, when it is then called a lingual cyst.
          • It is one of the most frequent congenital anomalies in the neck and is found along the midline most frequently below the hyoid bone

      • Face

        • occurs mainly between the 4th and 8th week

        • depends on the inductive influence of the prosencephalic and rhombencephalic organizing centers  brain development.

        • CNC

          the major source of connective tissue components, including cartilage, bone, and ligaments in the facial and oral regions.

        • myoblasts

          originating from paraxial and prechordal mesoderm, contribute to the craniofacial voluntary muscles.

        • The lower jaw and lower lip

          are the first parts of the face to form. They result from merging of the medial ends of the mandibular prominences in the median plane (will be discussed later......)

        • Craniofacial growth pattern

          • The first and general component accounting for most variation—is allometric

            – Brain growth predominates – flattening the cranial base – the displacement of the nasomaxillary segment; – growth of the orbital contents

          • The second component is alveolar remodeling

            – depends on the presence of tooth buds or teeth

          • The third component is mandibular condylar growth

        • Seraut Wajah

          • Mulut primitif

            • [end 3rd week] : stomodeum (calon oral&nasal cavities)

            • Berupa depresi ectoderm di bag.cephalic  kontak dg endoderm = buccopharyngeal membrane (BPM)/oropharygeal membrane

            • BPM akan jd lokasi tonsila, memisahkan stomodeum dg foregut

            • [4th week]: bpm ruptur  komunikasi stomodeum-GIT primitif

            • Note : before that: pbentukan hipofise anterior dr stomodeum ectoderm, b’evaginasi di atap mulut primitif (depan bpm).

              Jalur : rathke’s pouche

            • Terbentuk tonjolan2 sekitar stomodeum; = facial prominences (t.u CNC & arcus pharynx I*)

          • Facial prominences

            • produced mainly by the expansion of neural crest [4th week]:

            • 2 Maxillary = MXP [lateral]
            • 2 Mandibular = [caudal to maxillary]
            • The frontonasal prominence (FNP) [upperborder of stomodeum]
              • (FNP) surrounds the ventrolateral part of the forebrain the optic vesicles that form the eyes.
              • The frontal part of the FNP forms the forehead;

      • Palate

        • begins in the sixth week; but not completed until the 12th week.

        • The palate develops in two stages

          – The development of a primary palate

          – The development of a secondary palate

        • The critical period of palate development is from the end of the sixth week until the beginning of the ninth week.

        • Primary Palate

          • Early in the 6th week, the primary palate-median palatal process (intermaxillary segment)-begins to develop, by merging of the medial nasal prominence
          • = mass of mesenchyme between the internal surfaces of the maxillary prominences.
          • The primary palate forms the anterior/midline aspect of the maxilla, the premaxillary part of the maxilla).
          • It represents only a small part of the adult hard palate (i.e., anterior to the incisive fossa).
          • Between the 7th and 10th weeks , As a result of medial growth of the maxillary prominences, the two medial nasal prominences merge together at the midline
          • It is composed of
            • a labial componen  the philtrum of the upper lip;
            • an upper jaw component, which carries the four incisor teeth;
            • a palatal component,  the triangular primary palate.
            • intermaxillary segment is continuous with the rostral portion of the nasal septum, which is formed by the frontal prominence.

        • Secondary Palate

          • = the primordium of the hard and soft parts of the palate
          • The secondary palate begins to develop early in the sixth week
          • from two mesenchymal projections from the internal aspects of the maxillary prominences (lateral palatal processes/palatine shelves).
          • Shelves project inferomedially on each side of the tongue.
          • During the 7th and 8th weeks, the lateral palatal processes assume a horizontal position above the tongue  fuse along the palatine raphe  secondary palate
          • Primary&secondary fuse at foramen incisivus  definitive palate
          • Bone develop only in primary palate & anterior part of secondary palate  palatum durum (hard palate)
          • The rest : soft palate & uvula

        • Orofacial Cleft

          Failure of the facial prominences to merge or fuse results in abnormal developmental clefts. These clefts are due to the disruption of the many integrated processes of induction, cell migration, local growth, and mesenchymal merging

          • The nasal septum develops as a down growth from internal parts of the merged medial nasal prominences.
          • The fusion between the nasal septum and the palatal processes begins anteriorly during the 9 th week and is completed posteriorly by the 12th week, superior to the primordium of the hard palate.

      • Tooth

        • arise from an epithelial-mesenchymal (derived from neural crest Cells) interaction. All CT from CNC.
        • [6th week] : thickening of the epithelial lining of the oral cavity forms the dental lamina, along the length of the upper and lower jaws.
        • This lamina subsequently gives rise to a number of dental buds (@10)  primordia of the ectodermal components of the teeth.
        • deep surface of the buds invaginates  cap stage of tooth development  bell stage
        • Stage
          • Bud stage; 8 weeks.
          • B. Cap stage; 10 weeks.
          • C. Bell stage; 3 months.
          • D. 6 months.
        • Bagian

          • Enamel organ  enamel

            • Inner enamel epithelial :  ameloblast
            • Outer enamel epithelial  associated with capillary plexus

          • Dental papilla  dentin & pulp

            Dental follicle  cementum, periodeontal ligament, & adj.alveolar bone

      • Tongue

        • Near the end of the 4th week :
        • 1st : 2 lateral lingual swellings and 1 medial swelling (tuberculum impar). These three mesodermal swellings originate from the 1 st pharyngeal arch
        • Next : A 2nd median swelling (copula &hypobranchial eminence) by mesoderm of the second, third, and part of the fourth arch
        • 3rd median swelling, by the posterior part of the 4th arch  epiglottis
        • Oral part (anterior two thirds) of the tongue
          • The lateral lingual swellings rapidly increase in size, merge with each other , and overgrow (grow FASTER) the median lingual swelling. The merged lateral lingual swellings form the anterior two thirds (oral part) of the tongue  forming the median sulcus (midline groove )
        • Pharyngeal part (posterior one third) of the tongue
          • from the copula & hypobranchial eminence that develops in the floor of the pharynx associated with pharyngeal arches 2, 3, and 4. • The hypobranchial eminence overgrows the copula,  eliminating pharyngeal arch 2 in the formation of the definitive adult tongue.
        • The line of fusion of the anterior and posterior parts of the tongue is roughly indicated by a V -shaped groove-the terminal sulcus

      • Salivary Glands

        • [6-7th weeks] begin as solid epithelial buds from the primordial oral cavity
        • The club-shaped ends of these epithelial buds grow into the underlying mesenchyme.
        • The connective tissue in the glands is derived from neural crest cells.
        • All parenchymal (secretory) tissue arises by proliferation of the oral epithelium.

  • Month 3 to birth [fetus]

    • Early Tissue and Organ Differentiation
    • Trophoblast cells continue to invade uterine wall in the process of early placentation. Primary villi → 2nd
    • Within the conceptus, gastrulation converts the bilaminar embryo into the trilaminar embryo
    • Formation of notochord

  • Molecular Regulation

    The fate of cells is regulated by signalling molecules.

  • Growth factors

    • The growth factors involved in orofacial development belong mainly to four families that are well conserved between different species: – the Fibroblast Growth Factor (FGF) family, – the Hedgehog (HH) family, – the Transforming Growth Factor beta (TGF- β) family, which includes the Bone Morphogenetic Proteins (BMPs) and Activins – the Wingless (WNT) family
    • The FGF : facial epithelium and mesenchyme and mainly involved in stimulating cell proliferation
    • SHH is expressed in the ectoderm of the frontonasal and maxillary processes during development. SHH is also expressed at all stages of tooth development. (SHH plays a role in cell growth, cell specialization, and the normal shaping (patterning) of the body.)
    • TGF signalling pathway has major role in the molecular cascade that dictates craniofacial development. – TGF pathway may be also important in lip formation – several members of the BMP family have been shown to be expressed at various stages of tooth development.
    • WNT expression is often coincident with the expression of molecules of the Hedgehog and TGF-β families – This family also includes the Bone Morphogenetic Protein (BMP) and Activin signalling molecules transcription factors
    • Many transcription factors are important
    • The transcription factors MSX1 and PAX9 are responsible for partial tooth agenesis in humans. MSX1 is induced by BMP and FGF molecules and its mutation leads to selective absence of upper lateral incisors and/or upper and lower second pre-molar teeth
    • MSX1 mutations were also detected Point mutations in the TBX22 are found in 8% of cleft palate patients
    • IRF6 : provides instructions for making transcription factors that plays an important role in early development.  considered as a major gene causing approximately 12% of CL or CLP phenotypes