branchial arches

structures which develop in the head and neck regions of the embryo and give rise to internal and external structures found on the head, neck and upper thorax they appear at week 4 in humans following neurulation

pulmonary and cardiac vasculature bone and cartilage structures of head and neck musculature of head and neck structures and bones of inner and outer ear glandular structures including thyroid and thymus

initially 6 develop 5 is lost 4 and 6 fuses 4 remain form by lateral migration of neural crest cells

clefts

pouches

outer - skin of jaw, salivary glands, tooth enamel, buccal cavity inside - mandible maxilla

auditory tube

external components of middle ear and tympanum

skin of ear and neck

tonsils and lymphatics

thymus and thyroid

thyroid

a nerve supply and capacity for neurogenesis a bloody supply and capacity for driving angiogenesis cartillage and connective tissue

lined with ectodermal tissue on external surface, folds within tissues are called clefts lined with endodermal tissue on internal surface, folds within tissue are called pouches composed of mesoderm-derived mesenchyme tissue

arise from ectoderm at margins of the neural tube multipotent - differentiate to from different cell types differentiation if regulated by growth factors that control slug/snail zinc finger transcription factors which controls gene expression factors and cell fate neural crest cells drive branchial arch structural development explanted neural crest stem cell experiments with varied growth factor combinations promote formation of different cell types

branchial arch skeletal structure bones of the skull and face including the inner ear bone hyoid cartilage cartilage, bone, dentin, tendon, sensory neurons, dermis, meninges and glandular stroma humans and fish have some mirgration axes and in humans where gills would form, develop bones/ cartilage of the jaw, ear, neck and throat

the neural tube is segmented into rhombomeres during early development hox genes determine segmentation and neural crest cell properties within each rhombomere rhombomeres give rise to segmented brain structure and by migrating into specific branchial arches, cranial nerve 5, 7, 9 and 10 cerebellum, pons, medulla, cranial nerve 7 and 10 regulate breathing and heart rate combinations of hox genes expression patterns in each rhombomere determines segmentation and neural crest cell properties

branchial arches are located between the developing brain and heart neural crest cells migrate to form the vascular arch within each branchial arch anterior vascular arches from the major arteries of the head and neck posterior vascular arches link together to form the aortic arch at junction with the heart

3 populations of cardiac precursor cells - cardiac mesoderm cells - proepicardium - cardiac neural crest cells give rise to different lineages - pacemaker - atrial and ventricular cardiocytes - endocardial cells - valve components and connective tissues - smooth muscle cells - vascular endothelial cells

• e6.5 mouse/ e13-15 human: mesoderm projenitors ingress through the primitive streak and form the first primitive heart feild • e7.5 mouse/e19-20 human: ingress of cells from SHF form the outflow tract. the linear heart tube undergoes rightward looping to create the right and left ventricular chambers. at this stage primitive right and left atria are below ventricles • e10.5 mouse/e28 human: completion of cardiac looping creates the right and left chambers. CNC and PE cells migrate to create specific cardiac lineages • e14.5 mouse/e52 human: heart has 2 fully separated chambers and a separated outflow tract connected to the vascular structures which have arisen from branchial arches

growth factor combinations determine mesoderm differentiation into cardiac lineages BMP, NODAL-activin and SMAD, Wnt signalling, FGF

conserves pluripotent cells state by activating SMAD phosphorylation and transcription factor activin

canonical - Wnt binds to frizzled receptor, activation induces dishevelled to bind and inactivate Axin/APC/GSK3 complex. subsequent dephosphorylation of b catenin results in its stabilisation, accumulation in cytosol and nuclear migration in the nucleus b catenin is a coactivator of TCF/LEF which induces Wnt target gene expression non canonical - 1. wnt/ calcium pathway: Dv1 stimulates ER calcium release activating PK-C, calmodulin dependent kinase 2 and transcription factor NFAT signalling. regulates cytokinesis 2. wnt/planar cell polarity signalling - mediated by GTPases RhoA and Ras which induces RHoA-RHo associated kinase or janus kinase cytoskeletal rearrangement and contraction

FGF binds to TKRs activates autophosphorylation of tyrosine kinase FGFR kinase domain pattern of tyrosine auto-phosphorylation governs downstream signalling