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Embryology, Ectoderm

Editor: Leela Sharath Pillarisetty Updated: 5/1/2023 6:00:32 PM


This article will give a brief overview of the ectoderm, which is one of the three layers of the early tri-laminar embryo formed by gastrulation during early development. Normal embryonic development requires proper formation of the three layers and complex signaling between them. It will discuss the development, pathophysiology, and clinical significance of the ectodermal layer in the following paragraphs.


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Gastrulation is a phase that occurs during the third week of early embryonic development, and it takes place immediately after the blastula phase in most animals. Here, the single-layered and hollow blastula is rearranged and differentiated in the multi-layered gastrula with three distinct layers: the ectoderm, mesoderm, and endoderm. This differentiation is a change from homogenous, single layered cells into distinct cell lineages and also sets up the axis along which the embryo will continue to develop.[1]

Shortly after the gastrulation phase, the process of neurulation will occur. During this phase, mesodermal cells (middle layer from gastrulation) will form the notochord and will signal overlying ectodermal cells at the neural plate to fold inwardly to form the neural tube, and the joining ends will form the neural crest. The neural tube and neural crest detach from the rest of the overlying ectoderm. The neural tube will become the central nervous system. The neural crest will give rise to the peripheral nervous system, enteric nervous system, melanocytes, facial cartilage, odontoblasts, entero-chromaffin cells, spiral membrane, and more. The ectoderm that fails to involute will form the epidermis of the skin, hair, exocrine glands, and the anterior pituitary. Also, proper development requires communication between the three layers.


The neuro-ectoderm will form the neural tube and the neural crest. The neural tube will form the central nervous system (CNS: brain and spinal cord) and control most functions of the body and mind, including control of body movement, thoughts, and homeostasis. The peripheral nervous system (PNS) includes the nerves and ganglia outside of the CNS and divides into the somatic and autonomic nervous system. The primary function of the PNS is to connect the organs to the CNS, and it forms from the neural crest. The neural crest also gives rise to Schwann cells, chromaffin cells of the adrenal medulla, inner ear, cornea, odontoblasts, melanoblasts, pharyngeal arches, and the meninges of the brain and spinal cord. The surface ectoderm will give rise to the epidermis, external glands, hair, nails, anterior pituitary, and the apical ectodermal ridge amongst others. The functions of the surface ectoderm include hormone regulation by the adenohypophysis, acting as a barrier against the external involvement, and homeostasis.


Ectodermal differentiation towards the neural crest and neural tube route correlates with protein members of fibroblast growth factors (Fgf) which acts to modulate Bmp proteins (bone morphogenic proteins) simultaneously negatively.[1] At the same time, expression of Bmp and Wnt signals blocks FGF signals on ectodermal cells and permits it to continue towards a non-neural ectodermal lineage, including the epidermis.[2]


Although most cases of ectodermal dysplasia are diagnosed clinically after birth, there are other testing options available.  Sweat testing can be performed to identify female carriers of the X linked form of hypohidrotic ectodermal dysplasia. These carriers can have mild symptoms such as defective dentition or patchy and abnormal distribution of sweat glands.[3]

There is genetic testing available for various ectodermal dysplasia syndromes, although patients with a clinical diagnosis will not have their medical management changed due to further genetic testing. Therefore genetic testing is more useful for patients with mild or moderate symptoms for whom a genetic test will provide a definitive diagnosis.

Radioimmunoassay can also be done in some cases, such as to measure EDA levels with receptor-binding assays to help with diagnosing EDA deficiencies.[4]


The pathophysiology of ectodermal dysplasias involves a complex set of genes and gene products that result in alteration of pathways necessary for proper development of the ectoderm. One such gene us the EDA gene, which is a part of a group of genes that provide instructions for making proteins such as ectodysplasin A. Ectodysplasin A is part of a group of proteins that are important in signaling for the interactions between the ectoderm and the mesoderm. These interactions are essential for the formation of several structures that arise from the ectoderm, including the skin, hair, nails, teeth and sweat glands. Mutations in the EDA, EDAR or EDARADD gene results in defective ectodysplasin A formation thereby preventing normal interactions between these layers and therefore impairing normal ectodermal and mesodermal tissue development. Hypohidrotic ectodermal dysplasia is a disorder that has associations with a mutation in the EDA-Ectodysplastin A gene pathway.[5]

Clinical Significance

Ectodermal dysplasias are a rare group of conditions (over 200) that are due to abnormal development of ectodermal derived tissues, which can include the hair, teeth, nails, and glands. The conditions can have different genetic causes, but they share similar characteristics and present with a combination of symptoms. The diagnosis is made clinically. Ectodermal dysplasias are due to genetic defects on different chromosomes, and there have also been cases of spontaneous mutations. An example is hypohidrotic ectodermal dysplasia (HED) which is usually transmitted as an X-linked recessive trait can result from mutations in the EDA gene (as discussed above).  The reported prevalence of ectodermal dysplasias as approximately 7 out of 100000 newborns. [6]

Ectodermal dysplasias can be organized based off of their molecular pathways; some of them are listed below[7]:

EDA/NFKappaB pathway:

Christ-Siemens-Touraine syndrome—EDA

  • Presents with Hypohidrosis, hypotrichosis, hypodontia, smooth dry skin, craniofacial dysmorphology, periorbital pigmentation

Incontinentia Pigmenti—IKBKG

  • Presents with Short stature, cataracts, microphthalmia, hypodontia, thorax abnormalities, staged skin involvement, nail dystrophy, atrophic hair

Ectodermal dysplasia and immunodeficiency 1 (EDAID1)—IKBKG

  • Presents with hypohidrosis, hypotrichosis, and immunodeficiency

WNT pathway:

Goltz syndrome—PORCN

  • Presents with short stature, hearing loss, oral papillomas, hypodontia, syndactyly

Schopf-Schulz-Passarge syndrome—WNT10A

  • Hypodontia, eyelid cysts, keratoderma, hypoplastic nails, hypotrichosis

TP63 pathway:

ADULT syndrome—TP63

  • Lacrimal obstruction, hypodontia, dysplastic teeth, breast hypoplasia, ectrodactyly, thin skin, dysplastic nails 

Limb-mammary syndrome—TP63

  • Lacrimal duct atresia, hypodontia cleft p, hypoplastic breasts, syndactyly, ectrodactyly, nail dysplasia


Current management of ectodermal dysplasia syndromes focuses on multidisciplinary efforts from various specialists, including dermatologists, ENT specialists, pediatrics, psychologists, and dentists. It is essential to diagnose the syndrome early to initiate early interventions to prevent further derangements and to restore cosmetic features.



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Level 3 (low-level) evidence


Clarke A, Burn J. Sweat testing to identify female carriers of X linked hypohidrotic ectodermal dysplasia. Journal of medical genetics. 1991 May:28(5):330-3     [PubMed PMID: 1865470]

Level 3 (low-level) evidence


Podzus J, Kowalczyk-Quintas C, Schuepbach-Mallepell S, Willen L, Staehlin G, Vigolo M, Tardivel A, Headon D, Kirby N, Mikkola ML, Schneider H, Schneider P. Ectodysplasin A in Biological Fluids and Diagnosis of Ectodermal Dysplasia. Journal of dental research. 2017 Feb:96(2):217-224. doi: 10.1177/0022034516673562. Epub 2016 Oct 11     [PubMed PMID: 28106506]


Deshmukh S, Prashanth S. Ectodermal dysplasia: a genetic review. International journal of clinical pediatric dentistry. 2012 Sep:5(3):197-202. doi: 10.5005/jp-journals-10005-1165. Epub 2012 Dec 5     [PubMed PMID: 25206167]


Plottova-Puech I, Cambazard F. [Hypohidrotic ectodermal dysplasias]. Annales de dermatologie et de venereologie. 2002 Nov:129(11):1276-85     [PubMed PMID: 12514516]


Wright JT, Fete M, Schneider H, Zinser M, Koster MI, Clarke AJ, Hadj-Rabia S, Tadini G, Pagnan N, Visinoni AF, Bergendal B, Abbott B, Fete T, Stanford C, Butcher C, D'Souza RN, Sybert VP, Morasso MI. Ectodermal dysplasias: Classification and organization by phenotype, genotype and molecular pathway. American journal of medical genetics. Part A. 2019 Mar:179(3):442-447. doi: 10.1002/ajmg.a.61045. Epub 2019 Jan 31     [PubMed PMID: 30703280]