Some Recent Findings
- Molecular dynamics of Dkk4 modulates Wnt action and regulates meibomian gland development "Secreted Dickkopf (Dkk) proteins are major Wnt pathway modulators during organ development. Dkk1 has been widely studied and acts as a general Wnt inhibitor. However, the molecular function of other Dkks remains largely unknown. Here, we show that Dkk4 selectively inhibits a subset of Wnts, but is further inactivated by proteolytic cleavage. Meibomian gland (MG) formation is employed as a model where Dkk4 and its Wnt targets are expressed. Skin-specific expression of Dkk4 arrests MG growth at early germ phase, which is similar to that observed in Eda-ablated Tabby mice. Consistent with transient Dkk4 action, intact Dkk4 inhibits MG extension but the cleaved form progressively increases during MG development with a concomitant upswing in Wnt activity. Furthermore, both Dkk4 and its receptor (and Wnt co-receptor) Lrp6 are direct Eda targets during MG induction. In cell and organotypic cultures, Dkk4 inhibition is eliminated by elevation of Lrp6. Also, Lrp6 upregulation restores MG formation in Tabby mice. Thus, the dynamic state of Dkk4 itself and its interaction with Lrp6 modulates Wnt function during MG development, with a novel limitation of Dkk4 action by proteolytic cleavage."
- Involvement of Wnt, Eda and Shh at defined stages of sweat gland development "Sweat gland induction failed completely when canonical Wnt signaling was blocked in skin epithelium, and was accompanied by sharp downregulation of downstream Wnt, Eda and Shh pathway genes. The Wnt antagonist Dkk4 appeared to inhibit this induction: Dkk4 was sharply downregulated in β-catenin-ablated mice, indicating that it is induced by Wnt/β-catenin; however, its overexpression repressed Wnt target genes and significantly reduced gland numbers. Eda signaling succeeded Wnt. Wnt signaling was still active and nascent sweat gland pre-germs were still seen in Eda-null mice, but the pre-germs failed to develop further and the downstream Shh pathway was not activated. When Wnt and Eda were intact but Shh was ablated, germ induction and subsequent duct formation occurred normally, but the final stage of secretory coil formation failed. Thus, sweat gland development shows a relay of regulatory steps initiated by Wnt/β-catenin - itself modulated by Dkk4 - with subsequent participation of Eda and Shh pathways." (this same singling pathway is required for sensory Merkel cell development  )
- Hormones and the pilosebaceous unit "The skin, especially the pilosebaceous unit, can be regarded as an endocrine organ meanwhile a target of hormones, because it synthesizes miscellaneous hormones and expresses diverse hormone receptors."
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Search term: Gland Embryology | Integumentary Gland Development
- Human Embryology (2nd ed.) Larson Chapter 14 p443-455
- The Developing Human: Clinically Oriented Embryology (6th ed.) Moore and Persaud Chapter 20: P513-529
- Before We Are Born (5th ed.) Moore and Persaud Chapter 21: P481-496
- Essentials of Human Embryology Larson Chapter 14: P303-315
- Human Embryology, Fitzgerald and Fitzgerald
- Color Atlas of Clinical Embryology Moore Persaud and Shiota Chapter 15: p231-236
Development of Glands
Two main surface types, sweat and sebaceous, with a number of specialized glands in integumentary regions (lacrimal, Meibomian).
- both ectodermal in origin
- form as ingrowth of ectoderm into the mesoderm
Humans have two types of sweat glands are present in humans, differing in secretory mechanism, number, histological appearance and sweat composition.
- merocrine (~eccrine) sweat glands (majority)
- apocrine sweat glands (minority)
- apocrine in axilla, pubic and nipple regions
- see also mammary gland development
Skin merocrine sweat gland
Skin merocrine sweat gland
Skin merocrine sweat gland
Skin merocrine sweat gland (detail)
Adult skin sebaceous gland histology
- associated with hair development
- except plans penis and labia minora
- these glands secrete vernix
(vernix, Latin, vernix = varnish, caseous = cheese=like) This is a specialized coating that forms in late development over the entire fetal surface. The main component, secreted sebum, is secreted by sebaceous glands. The other constituents are cells sloughed off the fetus's skin, and shed lanugo hair. The coating also has a high water content (80%) largely compartmentalized within fetal corneocytes (cells forming the stratum corneum).
This coating develops intially in a cranio-caudal direction and can be absent in preterm infants.
Some functions include:
- protection of the fetal skin from extraembryonic fluids amnion, urine
- providing a slippery surface helps with parturition (birth)
- acting as a biofilm barrier against infection
Lacrimal glands produce the aqueous tears that mix with Meibomian glands secretions to form a tear film coating the outer surface of the eye.
Human Development (based upon data from)
- Carnegie stage 16 - 18 - formation of the lacrimal lamina
- Carnegie stage 19 - 23 - formation of the lacrimal cord
- fetal Week 9+ - maturation of the excretory lacrimal system
- Links: vision
The Meibomian glands (glandulae tarsales) are sebaceous glands located at the margins of the upper and lower eyelids of humans and mammals. The gland cells (meibocytes) secrete by a holocrine mechanism and produce constantly a lipid-rich secretion (meibum) that mix with with aqueous tears produced by lacrimal glands. These glands are also regulated through sex hormones, androgens have a supporting function while estrogens act antagonistically.
The glands were first described in 1666 by Heinrich Meibom (1638 - 1700) a German physician and anatomist.
Term describes a range of abnormalities associated with lacrimal gland development. The most common genetic cause of alacrima is the Riley-Day syndrome.
Nasolacrimal Duct Obstruction
Drainage duct obstruction can be a common anomaly in children and can be caused by inflammation or fibrosis without any precipitating cause (primary classification) or by an acquired lacrimal drainage obstruction (secondary classification).
Vernix Caseosa Peritonitis
Not an abnormality of development, but a clinical term for a rare post-caesarean section complication due to spilt vernix caseosa at the time of caesarean section mediating a maternal inflammatory reaction.
- ↑ Sima J, Piao Y, Chen Y & Schlessinger D. (2016). Molecular dynamics of Dkk4 modulates Wnt action and regulates meibomian gland development. Development , 143, 4723-4735. PMID: 27864382 DOI.
- ↑ Cui CY, Yin M, Sima J, Childress V, Michel M, Piao Y & Schlessinger D. (2014). Involvement of Wnt, Eda and Shh at defined stages of sweat gland development. Development , 141, 3752-60. PMID: 25249463 DOI.
- ↑ Xiao Y, Thoresen DT, Miao L, Williams JS, Wang C, Atit RP, Wong SY & Brownell I. (2016). A Cascade of Wnt, Eda, and Shh Signaling Is Essential for Touch Dome Merkel Cell Development. PLoS Genet. , 12, e1006150. PMID: 27414798 DOI.
- ↑ Chen WC & Zouboulis CC. (2009). Hormones and the pilosebaceous unit. Dermatoendocrinol , 1, 81-6. PMID: 20224689
- ↑ Pickens WL, Warner RR, Boissy YL, Boissy RE & Hoath SB. (2000). Characterization of vernix caseosa: water content, morphology, and elemental analysis. J. Invest. Dermatol. , 115, 875-81. PMID: 11069626 DOI.
- ↑ de la Cuadra-Blanco C, Peces-Peña MD, Jáñez-Escalada L & Mérida-Velasco JR. (2006). Morphogenesis of the human excretory lacrimal system. J. Anat. , 209, 127-35. PMID: 16879594 DOI.
- ↑ Butovich IA. (2009). The Meibomian puzzle: combining pieces together. Prog Retin Eye Res , 28, 483-98. PMID: 19660571 DOI.
- ↑ Stuart OA, Morris AR & Baber RJ. (2009). Vernix caseosa peritonitis - no longer rare or innocent: a case series. J Med Case Rep , 3, 60. PMID: 19208257 DOI.
Takahashi Y, Kakizaki H, Chan WO & Selva D. (2010). Management of congenital nasolacrimal duct obstruction. Acta Ophthalmol , 88, 506-13. PMID: 19681790 DOI.
Weber AL, Rodriguez-DeVelasquez A, Lucarelli MJ & Cheng HM. (1996). Normal anatomy and lesions of the lacrimal sac and duct: evaluated by dacryocystography, computed tomography, and MR imaging. Neuroimaging Clin. N. Am. , 6, 199-217. PMID: 8919141
Moore BD. (1994). Lacrimal system abnormalities. Optom Vis Sci , 71, 182-3. PMID: 8196943
Rowzee AM, Lazzarino DA, Rota L, Sun Z & Wood TL. (2008). IGF ligand and receptor regulation of mammary development. J Mammary Gland Biol Neoplasia , 13, 361-70. PMID: 19020961 DOI.
Singh G & Archana G. (2008). Unraveling the mystery of vernix caseosa. Indian J Dermatol , 53, 54-60. PMID: 19881987 DOI.
Tollin M, Bergsson G, Kai-Larsen Y, Lengqvist J, Sjövall J, Griffiths W, Skúladóttir GV, Haraldsson A, Jörnvall H, Gudmundsson GH & Agerberth B. (2005). Vernix caseosa as a multi-component defence system based on polypeptides, lipids and their interactions. Cell. Mol. Life Sci. , 62, 2390-9. PMID: 16179970 DOI.
Search Pubmed: Epithelial Gland Development | Sweat Gland Development | Sebaceous Gland Development | Eccrine Gland Development | Apocrine Gland Development | Lacrimal Gland Development | Meibomian Gland Development
- acrosyringium - coiled intra-epidermal region of the eccrine gland sweat duct.
- apocrine gland - (sweat gland) proteinaceous secretion associated with hair (axilla, areola, genital and anal regions). Additional glands associated with eyelashes are called the glands of Moll (ciliary gland). (More? image - apocrine secretion)
- arrector pili muscle - bundle of smooth muscle associated with hair follicle, inserts into the papillary layer of the dermis and attaches to the dermal sheath of the hair follicle. (More? image - arrector pili muscle)
- Blaschko lines - (lines of Blaschko) may represent pathways of epidermal cell migration and proliferation during development. Specific type of lupus erythematosus shows this distinctive pattern. Named after Alfred Blaschko a German dermatologist who first described the feature in 1901. (More? PMID 21396561 | Historic Terminology)
- bulb - the hair follicle enlargement located at its deepest end, dividing cells form the hair and the root sheath.
- café-aut-lait macule - (French, cafe-au-lait = coffee with milk; birthmark) describes the characteristic colour of the skin hyperpigmented patch present at birth (congenital) or appearing in early infancy. Common single feature, multiple are associated with various genetic syndromes including Neurofibromatosis type 1 and 2.
- corneocytes - terminally differentiated keratinocytes forming the stratum corneum.
- cutis - alternative term for the epidermis and the dermis layers of the skin.
- dermal papillae - interdigitation of the dermis with the epidermis.
- dermatoglyphic patterns - (Greek, derma = "skin", glyph = "carving") fingers, palms, toes, and soles skin patterns.
- dermis - connective tissue middle layer of the skin, consists of two sublayers (papillary and reticular layers) that do not have a clear boundary. Embryologically derived from the somite dermatome.
- dermomyotome - Early embryonic dorsolateral half of the somite that will later divide to form both the dermatome and myotome. The dermatome will contribute the dermis and hypodermis of the skin. The myotome will contribute the skeletal muscle of muscoloskeletal system. Development sequence: mesoderm to paraxial mesoderm to somite to "dermomyotome" then dermatome and myotome. (More? Somitogenesis | Musculoskeletal System Development | Integumentary System Development)
- eccrine gland (Greek, ekkrinein = "secrete"; merocrine glands) sweat glands unique to some primates and used in humans for thermoregulation. Adult body has 2 to 4 million sweat glands with concentrations (700/cm) on the palms of the hand, soles of the feet and forehead. Secretion is timulated by sympathetic nervous system, post-ganglionic cholinergic branch, and other stimuli
- ephilis - (pl., ephilides; freckle) Clinical term describing a "freckle", that is a small brown or tan mark on the skin. These inherited features result from a copy of variant Melanocortin 1 Receptor (MC1R) gene and are common on fair skinned Celtic children. Melanocytes produce locally more melanin, this can also increase following exposure to ultraviolet radiation in sunlight. (More? Integumentary | Neural Crest | OMIM MC1R)
- epidermis - Histological term describing the external cellular epithelial layer of the integumentary (skin) covering the entire body. This surface layer of keratinocytes is ectoderm in origin, while the underlying connective tissue layers of dermis and hypodermis are mesoderm in origin. (More? Integumentary Development)
- epidermal differentiation complex - (EDC) human chromosome (1q2) containing linked 63 genes within four gene families that are molecular markers for stratified epidermis terminal differentiation.
- epidermal growth factor receptor - expressed on cells in the epidermis basal layer, signaling stimulates both epidermal growth and wound healing and also mediates an inhibition of differentiation.
- glabrous skin - skin without hair, refers to the palms of hands and soles of feet.
- hair - (pili) in humans consists of vellus and terminal hairs.
- holocrine - form of gland secretion where the secretory cells eventually lyse (rupture) and are lost. On the skin, these cells release sebum consisting mainly of lipid. (More? image - holocrine secretion)
- hypodermis - (subcutis, subcutaneous adipose) a connective tissue ilower layer of the skin that binds it to underlying structures.
- integumentary - term for the skin and its appendages.
- involucrin - protein that binds loricrin in the development of the cell envelope protecting corneocytes in the skin.
- keratinocyte - the main cell type forming the layers of the epidermis, derived from ectoderm.
- keratohyalin granule - found in the stratum granulosum consist of profilaggrin and loricrin.
- Langerhans cell - skin dendritic cell (antigen presenting cell) develops initially from fetal liver monocytes and yolk sac macrophages. May, depending on the immunological setting, elicit immunity or tolerance. Named after Paul Langerhans.
- Langer's lines - (skin cleavage lines, cleavage lines) Clinical term for the orientation of reticular dermis collagen bundles causing tensions on skin and subcutaneous tissues. Lines tend to be horizontal in the trunk and neck, and longitudinal in the skin and limbs. (More? PMID 15791423)
- Meissner corpuscle - sensory structure acting as a rapidly-adapting mechanoreceptor mainly in the dermal papillae of (digital) skin. (More?Touch
- melanin - (Greek, melanos = black) The pigment produced by melanocytes that provides photoprotection, preventing cellular DNA damage, and colouring of the basal epithelial cells that absorb the pigment.
- melanodermia - hyperpigmentation causing abnormal darkening (brown/black) of the skin due to excess melanin or by metallic substances. See also the abnormality ceruloderma (blue/grey). (More? PMID 23522626)
- melanocyte - (Greek, melanos = black) A pigmented cell, neural crest in origin, differentiating from melanoblasts located in the skin and other tissues that produces melanin. The melanocytes within the integument (skin) transfer melanin to keratinocytes to give skin colour and to the hair follicle to give hair colour. Melanocytes are also located within "non-cutaneous" tissues in the eye (for eye colour), harderian gland and inner ear. This is the cell type that proliferates in the cancer melanoma. (More? Neural Crest Development | Integumentary System Development)
- Merkel cell - An epidermal-derived cell in touch-sensitive area of the epidermis and mediate mechanotransduction in the skin. Previously thought to be neural crest in origin, but recently shown to arise from the embryonic epithelium. The cells are named after Friedrich Sigmund Merkel, a German anatomist who was the first to describe them in 1875. (More? Touch | Lecture - Integumentary Development | PMID 19786578 | PMID 3782861)
- merocrine gland - (sweat gland, eccrine sweat) simple tubular glands located at the border between the dermis and hypodermis. These glands regulate the body temperature. (More? image - merocrine secretion)
- nestin - (neuroectodermal stem cell marker) an intermediate filament protein (type VI) expressed in stem cells and transiently during development, and in cells within hair follicles, sebaceous and sweat glands.
- papillary layer - dermis sublayer that appears less dense and contains more cells lying close beneath the epidermis. (More? image)
- pilosebaceous unit - term used to describe a hair and its associated structures: hair follicle, arrector pili muscle and sebaceous gland.
- rete ridge - the extensions of the epidermis into the dermis. These epidermal surface thickenings extend downward between underlying connective tissue dermal papillae. This is also the site of initial eccrine gland differentiation.
- reticular layer - dermis sublayer that appears denser and contains fewer cells with thick collagen bundles lying beneath the papillary layer parallel to the skin surface. (More? image)
- root sheath - cell layers that surround the hair.
- sebaceous gland - holocrine gland associated with both the hair follicle and hairless parts of the skin (lips, cheek oral surface and external genitalia). Embedded in the dermis and are sites of infections (acne).
- simple - consisting of a single cell layer.
- terminal hairs - hair seen in obviously hairy parts of the body.
- thick skin - refers to the skin histology found on the palms of the hand and soles of the feet, does not contain hair. Note that this is used as a histological term not a measurement of overall skin thickness.
- thin skin - refers to the skin histology found on skin on all body regions, other than palms and soles (thick skin).
- vellus hairs - fine short hairs only lightly pigmented covering the body.
- vernix caseosa - (vernix, Latin, "caseosa" = cheese-like) a fetal protective coating consisting of sebum, skin cells and lanugo hair. Forming late in fetal development in a rostra-caudal sequence associated with epithelium differentiation.
- Voigt's lines - clinical term to describe the skin borders between areas of innervations by specific peripheral cutaneous nerves. (More? Sensory Touch | Historic Terminology)
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