Developmental Biology Biology Ectodermal Organs. November 22, 2005

Transcription

1 Developmental Biology Biology 4361 Ectodermal Organs November 22, 2005

2 Germinal neuroepithelium external limiting membrane neural tube neuroepithelium (stem cells) Figure 13.3

3 Figure 13.4 Neuroepithelial derivatives

4 Figure 13.5 Myelination

5 Human spinal cord development neurons in alar and basal plate glial cells in floor and roof plate mantle (gray matter) neurons bodies marginal layer (white matter) myelinated axons Figure 13.7

6 Human spinal cord development in afferent receive impulses from skin, muscles, organs out efferent send signals to muscles and glands commissural axons connect afferent and efferent signaling centers Figure 13.7

7 Establishment of dorso ventral pattern in spinal cord notochord graft experiment floor plate induction efferent neuron induction notochord removal experiment no floor plate/efferent neurons extended midrange floor plate graft experiment additional floor plate additional efferent neurons notochord/floor plate Figure 13.8 = ventralize neural tube = efferent neurons, no afferent neurons

8 Establishment of dorso ventral pattern in spinal cord Inductive signals: Ventral (floor plate & efferent neurons) sonic hedgehog (Shh) chordamesoderm notochord floor plate Dorsal (roof plate, afferent neurons, neural crest) BMPs, Wnt family epidermal ectoderm roof plate NOTE antagonistic signals! Figure 13.10

9 Shh morphogen gradient increasing concentration of Shh induces distinct types of neurons in vitro Shh and dorsalizing signals interact to specify a dorsoventral pattern of motor neurons, interneurons & spinal cord Figure Figure 13.11

10 Spinal cord

11 Nervous system

12 Vertebrate brain development brain develops from cranial part of neural tube dorsoventral pattern is induced by same molecular mechanisms as spinal cord however, organanization is different central canal forms fluid filled spaces (ventricles) brain regions have different structures/functions further differentiation of gray and white matter

13 Figure Vertebrate brain development

14 Vertebrate brain development Brain development in vertebrates 2 Figure week human embryo

15 Vertebrate brain development 5 week human embryo Figure 13.12

16 Figure Vertebrate brain development

17 Myelencephalon medulla oblongata human 6 wk Figure 13.14

18 Mesencephalon metencephalon cerebellum human 8 wk human 4 month Figure 13.15

19 Brain development cerebellum 8 wk 12 wk 13 wk 15 wk Figure 13.16

20 Vertebrate brain development 5 week human embryo prosencephalon: diencephalon optic cup telencephalon cerebrum (2 hemispheres) Figure 13.12

21 Diencephalon & telencephalon human 8 wk Brain architecture: nuclei areas with specific functions gray matter migration/stratification vertical neurons move outward horizontal (6 layers) Figure 13.17

22 Human brain development

23 Vertebrate brain development main portion of the cerebrum; covers most other parts of the brain extends into olfactory bulb, sense of smell gateway for sensory fibers from spinal cord regulatory center for visceral functions forms posterior lobe of pituitary gland endocrine organ circadian rhythm, annual repro. relay station for visual and auditory reflexes coordination center for posture and movement pathway for nerve fibers controls reflexes of neck, throat, tongue Figure spinal cord mediates reflexes of trunk and appendages

24 Human brain development 4 month human fetus all major brain areas developed Figure 13.19

25 Peripheral nerves

26 Cranial Nerves

27 Neural crest origins Neural crest cells: only found only in vertebrates originate from cells located between epidermal and neural ectoderm migrate to different positions within the body variety of fates head cartilage pigment cells neurons hormone producing gland cells smooth muscle cardiovascular system Figure 13.22

28 Embryonic origin of neural crest cells Figure Juxtaposition hypothesis: NC cells arise at boundary between neural plate and epidermis both grafts in this experiment will give rise to NC cells NC cells are induced by local interactions between neural plate and epidermis

29 Neural crest cell fate mapping Methods used to monitor NC cell migration: fluorescent dyes & immunostaining homotopic transplantation from radiolabeled donor to non labeled host genetic labels: e.g. transplantation between quail and chicken Figure 13.25

30 Neural crest transplantation chick / quail chimera

31 Neural crest cell migration Migration NC cells lose epithelial connections, cell adhesion properties migrate onset of migration controlled by regulatory gene slug+ slug expression causes dissociation of desmosomes slug may activate other regulatory genes involved in migration Migration routes Trunk NC cells dorsolateral skin melanocytes, xanthophores ventral neurons, glial cells, visceral nervous system Figure 13.27

32 Neural crest cell fates Cranial pigment cells sensory cranial ganglia parasympathetic ganglia hormone producing cells bones, connective tissue Trunk melanocytes, xanthophores neurons, glial cells visceral nervous system sympathetic parasympathetic Schwann cells adrenal medulla Figure Cardiac (overlapping head and trunk) connective tissue, muscle of large blood vessels cartilage and other connective tissue melanocytes neurons

33 NC fate and potency NC Cell Potency: (determined by heterotopic transplantation): cranial cartilage only from head NC cells some cardiovascular structures limited to cardiac NC all other NC derivatives can be formed by NC cells from anywhere along the anterior posterior axis Are NC cells pluripotent? Figure 13.28

34 Neural crest cell determination Pluripotency hypothesis each NC cell has the potential to form many or all derivatives external signals cause their determination Selection hypothesis all NC regions contain mixed populations of determined cells, each of which has just one fate external signals limit NC cells to certain migration pathways and differentiation patterns Figure 13.29

35 NC cell determination Clonal analysis in vitro: NC cells proliferate and form clones some clones differentiate into only one or two cell types most clones differentiate into several cell types many NC cells are originally pluripotent NC cell fate becomes restricted in a stepwise process

36 NC cell determination Clonal analysis in vivo: clones from pre migratory NC cells usually contain several cell types clones from older, migratory NC cells often contain more than one cell type most NC cells are pluripotent Double labeling experiments: descendants of a single NC cell can be located in different tissues dorsal root ganglion ventral root sympathetic ganglion Figure 13.30

37 Spatial restrictions on NC cell migration NC cells follow defined migration routes: avoid notochord area inhibitory signal from notochord chondroitin sulfate containing glycoprotein ventrally migrating trunk NC cells pass through anterior halves of somites, not through posterior halves inhibition by somitic mesoderm repulsive guidance by ephrins and their receptors Figure 13.27

38 Temporal restrictions to NC cell migration Figure NC cells behave according to their age: chicken NC cells enter ventral pathway first, then dorsolateral pathway isolated NC cells aged in vitro, then transplanted into hosts at various stages of NC cell migration transplanted aged NC cells behave according to their age, not according to surrounding host NC cells

39 ECM influence on NC cell determination nitrocellulose microcarriers coated with ECM components from: dorsolateral pathway (pigment cell route) ventral pathway (dorsal root ganglia route) dorsolateral ECM components induce NC cells into pigment cells Figure ventral ECM components induce NC cells into neurons

40 Extracellular matrix (ECM) ECM fibrous and gelatinous material released from cells amorphous ground substance (attracts water; forms gel) fibers (form meshwork; resist expansion) provide multiple binding domains ECM functions: basement membrane matrix for bones and teeth tendons tensile strength cornea forms transparent layer influences cell division, shape, movement, differentiation (binding sites for growth factors, etc.) Ground substance: glycosaminoglycans, proteoglycans amorphous, hydrophilic hyaluronic acid heparin Fibrous components: glycoproteins collagen fibronectin laminins

41 ECM influence on NC cell determination nitrocellulose microcarriers coated with ECM components from: dorsolateral pathway (pigment cell route) ventral pathway (dorsal root ganglia route) dorsolateral ECM components induce NC cells into pigment cells Figure ventral ECM components induce NC cells into neurons

42 Factors affecting NC cell migration & determination Migration: subpopulation of NC cells diffusible signals from notochord, somites and potentially other tissues age of NC cells Determination: subpopulation of NC cells contact signals provided by ECM components region specific growth factors ( endothelins, TGF β superfamily & others)

43 squamous columnar Ectodermal placodes Figure areas of ectoderm in head region induced by underlying parts of the brain epibranchial placodes contribute to sensory ganglia of cranial nerves dorsolateral placodes contribute to sensory ganglia of cranial nerves form parts of ear, eye and nose

44 Otic placode Figure forms otic pit otic vesicle inner ear induced by rhombencepahlon & mesoderm otic vesicle expands unequally into complicated shape; forms the labyrinth

45 Otic placode labyrinth formation Labyrinth: (higher vertebrates) squamous and columnar epithelia form sensory epithelia registration of gravity & acceleration in semicircular canal perception of sound in cochlea transmission of sounds to inner ear by tiny bones and membranous window of middle ear Figure 13.35

46 Lens placode induced by complex interactions of head ectoderm with pharyngeal endoderm, heart mesoderm, neural crest & optic vesicle invaginates to form the lens vesicle Figure 1.16 lens vesicle cells differentiate into lens fibers synthesis of crystallins

47 Lens placode eye development eye development requires simultaneous development of lens vesicle and optic cup outer layer of the optic cup forms the pigment layer of the retina inner layer of optic cup: neural layer of retina converging axons form the optic nerve opening of the optic cup forms the pupil Figure 13.36

48 Neural retina human 25 wk Figure13.37

49 Nasal placode 5 weeks 6 weeks 7 weeks 10 weeks placodes surrounded by swellings (ridges) increase in size of maxillary swellings pushes nasal swellings towards center forms lateral & medial nasal swellings & nasal pit (placode forms floor) induced by underlying endoderm and telencephalon fusion forms nose, lip (partial), jaw (partial), palate (partial) fusion defects: harelip Figure 13.39

50 Nasal placodes nose formation 6 weeks oronasal membrane between nasal pit and oral cavity ruptures to form the primary choanae 7 weeks nasal chambers elongate while secondary palate & secondary choanae form 9 weeks epithelium of the nasal pit forms the olfactory epithelium which lines the roof of the nasal chambers Figure 13.40

51 Epidermis largest ectodermal derivative outer layer of the skin periderm temporary outer layer differentiation germinative layer or basal layer progenitor cells differentiate into epidermal cells keratin synthesis in granular layer cornified layer dead keratin sacs Figure mesenchymal dermis supports the epidermis and induces formation of hair, feathers, scales & glands

52 Epidermis hair development Hair development in humans: dermal mesenchyme cells induce formation of epidermal hair buds dermal mesenchyme cells are enclosed by base of hair bud = hair papilla hair papilla and differentiated epidermal cells form the = hair follicle core cells of hair follicle are keratinized and pushed outside = hair shaft differentiation of blood vessels, nerve endings & associated glands Figure 13.42

53 Epidermis hair development core cells of the hair follicle are keratinized and pushed outside = hair shaft melanocytes transfer pigment to hair secretes the oily sebum sebum + shed peridermal cells = vernix caseosa bulb containing pluripotent hair follicle stem cells Figure root sheath is formed by epidermal and mesencymal cells

54 Mammary gland development 7 wk human (generalized mammal) Figure13.43