Integumentary System - Nail Development

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Neonatal nail histology
Neonatal nail

This page introduces the development of nails, fingernails and toenails, these integumentary specializations in other species have been specialised as claws and hooves.

Each nail is convex on its outer surface, concave within, and is implanted by a portion, called the root, into a groove in the skin; the exposed portion is called the body, and the distal extremity the free edge.

Integumentary Links: integumentary | Lecture | hair | tooth | nail | integumentary gland | mammary gland | vernix caseosa | melanocyte | touch | Eyelid | outer ear | Histology | integumentary abnormalities | Category:Integumentary
Hair Links  
Hair Links: Overview | Lanugo | Neonatal | Vellus | Terminal | Hair Follicle | Follicle Phases | Stem Cells | Molecular | Pattern | Puberty | Histology | Hair Colour | Arrector Pili Muscle | Hair Loss | Integumentary
Touch Links  
Touch Links: Touch Receptors | Touch Pathway | Pacinian Corpuscle | Meissner's Corpuscle | Merkel Cell | Sensory Modalities | Neural Crest Development | Neural System Development | Student project | Integumentary | Sensory System
Historic Embryology - Integumentary  
1906 Papillary ridges | 1910 Manual of Human Embryology | 1914 Integumentary | 1923 Head Subcutaneous Plexus | 1921 Text-Book of Embryology | 1924 Developmental Anatomy | 1941 Skin Sensory | Historic Disclaimer


Some Recent Findings

  • Lgr6 marks nail stem cells and is required for digit tip regeneration PNAS Oct 2015 "The tips of the digits of some mammals, including human infants and mice, are capable of complete regeneration after injury. This process is reliant on the presence of the overlaying nail organ and is mediated by a proliferative blastema. Epithelial Wnt/β-catenin signaling has been shown to be necessary for mouse digit tip regeneration. Here, we report on Lgr5 and Lgr6 (leucine-rich repeat-containing G protein-coupled receptor 5 and 6), two important agonists of the Wnt pathway that are known to be markers of several epithelial stem cell populations. We find that Lgr5 is expressed in a dermal population of cells adjacent to the specialized epithelia surrounding the keratinized nail plate. Moreover, Lgr5-expressing cells contribute to this dermis, but not the blastema, during digit tip regeneration. In contrast, we find that Lgr6 is expressed within cells of the nail matrix portion of the nail epithelium, as well as in a subset of cells in the bone and eccrine sweat glands. Genetic lineage analysis reveals that Lgr6-expressing cells give rise to the nail during homeostatic growth, demonstrating that Lgr6 is a marker of nail stem cells." Moreover, Lgr6-expressing cells contribute to the blastema, suggesting a potential direct role for Lgr6-expressing cells during digit tip regeneration. This role is confirmed by analysis of Lgr6-deficient mice, which have both a nail and bone regeneration defect. OMIM LGR6
More recent papers  
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Search term: Nail Embryology | Nail Development |

Older papers  
These papers originally appeared in the Some Recent Findings table, but as that list grew in length have now been shuffled down to this collapsible table.

See also the Discussion Page for other references listed by year and References on this current page.

  • Frizzled6 (Fzd6) deficiency disrupts the differentiation process of nail development[1] "Immunohistochemical studies revealed decreased expression of Krt86, Krt6b, and involucrin in the epidermal portion of the claw field in the knockout embryos. We further showed that Dkk4, a Wnt antagonist, was significantly downregulated in Fzd6(-/-) mice along with Wnt, Bmp, and Hh family genes; and Dkk4 transgenic mice showed a subtly but appreciably modified claw phenotype. Thus, Fzd6-mediated Wnt signaling likely regulates the overall differentiation process of nail/claw formation."
  • Incomplete development of the nail of the hallux in the newborn.[2] "Between March and October 2008, the nails of 541 (252 females, 289 males) consecutively born neonates with an average age of 3.2 days were examined in the Neonatology Unit. Of these newborns with nail disorders, 36 were re-examined after a period that ranged from seven days to six months. The most frequent nail alteration was the incomplete development of the hallux nail, which was triangular - sometimes trapezoidal - shaped. This alteration, which had been previously reported in the literature as congenital hypertrophy of the lateral folds of the hallux, spontaneously regressed within one to three months in the infants re-examined. There was no associated inflammation or onychocryptosis at any time. The apparent hypertrophy of the nail folds seemed to be secondary to the lack of pressure of the nail lamina."
  • Lyonization pattern of normal human nails.[3] "To examine the X-inactivation patterns of normal human nails, we performed the human androgen receptor gene assay of DNA samples extracted separately from each finger and toe nail plates of nine female volunteers. The X-inactivation pattern of each nail was unique and constant for at least 2 years. ...These findings suggest that the composition of precursor cells of each nail is maintained at each site at least through several cycles of regeneration time, and that the nail plate has a longitudinal band pattern, each band consisting of cells with only one of the two X-chromosomes inactivated."


The Nail
  • 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 Overview

Fingernail cartoon.jpg
  • Forelimb before hindlimb - week 10 fingernails, week 14 toe nails
  • nail field - appears at tip and migrates to dorsal surface
  • thickened epidermis - surrounding cells form nail fold
  • keratinization of proximal nail fold forms nail plate

Nails reach Digit Tip

  • week 32 fingernails
  • week 36 toenails

Note that nail growth can be used as an indicator of prematurity.


In a study of 500+ neonates, the most frequent nail alteration identified was the incomplete development of the hallux (big toe) nail, appearing as either triangular or trapezoidal - shaped.[2]

Ectopic Nail

Ectopic nail.jpg

Congenital ectopic nails are an extremely rare deformity.[4]


A very rare abnormality resulting in an absence of nails. Can result from both genetic and environmental defects and be associated with a range of other abnormalities. Simple anonychia is the congenital absence of the nails without any other coexisting major congenital anomaly.


Nail Patella Syndrome

Nail Patella Syndrome
Nail Patella Syndrome[5]

(NPS) rare (1/50,000) Autosomal dominant disorder characterized by hypoplastic or absent patellae, dystrophic nails, dysplasia of the elbows and iliac horns. Potentially due to mutations in LMX1B, a LIM-homeodomain transcription protein.

Links: Nail Development | OMIM - nail-patella syndrome | OMIM - LMX1B | GeneReviews

Ectodermal dysplasias

Witkop syndrome

An autosomal dominant genetic disorder characterized by the absence of several teeth and abnormalities of the nails.


  1. Cui CY, Klar J, Georgii-Heming P, Fröjmark AS, Baig SM, Schlessinger D & Dahl N. (2013). Frizzled6 deficiency disrupts the differentiation process of nail development. J. Invest. Dermatol. , 133, 1990-7. PMID: 23439395 DOI.
  2. 2.0 2.1 Milano A, Cutrone M, Laforgia N & Bonifazi E. (2010). Incomplete development of the nail of the hallux in the newborn. Dermatol. Online J. , 16, 1. PMID: 20579456
  3. Okada M, Nishimukai H, Okiura T & Sugino Y. (2008). Lyonization pattern of normal human nails. Genes Cells , 13, 421-8. PMID: 18429815 DOI.
  4. Feily A, Ayoobi A, Yaghoobi R & Kheradmand P. (2009). A case of congenital ectopic nails on the bilateral second fingers without bone deformity. Indian J Dermatol Venereol Leprol , 75, 525-7. PMID: 19736447 DOI.
  5. Senguttuvan NB, Sivaraman A, Kandasamy D & Marimuthu K. (2011). Nail patella syndrome: a rare cause of renal failure in a young adult. Pan Afr Med J , 9, 31. PMID: 22145064



Smith RJ & Rubin AI. (2020). Pediatric nail disorders: a review. Curr. Opin. Pediatr. , 32, 506-515. PMID: 32692049 DOI.

Bergqvist C, Ramia P, Abbas O & Kurban M. (2017). Genetics of syndromic and non-syndromic hereditary nail disorders. Clin. Genet. , 91, 813-823. PMID: 27613389 DOI.

Piraccini BM & Starace M. (2014). Nail disorders in infants and children. Curr. Opin. Pediatr. , 26, 440-5. PMID: 24886951 DOI.

Harrison S & Bergfeld WF. (2009). Diseases of the hair and nails. Med. Clin. North Am. , 93, 1195-209. PMID: 19932326 DOI.

Duverger O & Morasso MI. (2008). Role of homeobox genes in the patterning, specification, and differentiation of ectodermal appendages in mammals. J. Cell. Physiol. , 216, 337-46. PMID: 18459147 DOI.

van Steensel MA, van Geel M & Steijlen PM. (2004). Molecular genetics of hereditary hair and nail disease. Am J Med Genet C Semin Med Genet , 131C, 52-60. PMID: 15468149 DOI.

Hamrick MW. (2003). Evolution and development of mammalian limb integumentary structures. J. Exp. Zool. B Mol. Dev. Evol. , 298, 152-63. PMID: 12949775 DOI.

Hamrick MW. (2001). Development and evolution of the mammalian limb: adaptive diversification of nails, hooves, and claws. Evol. Dev. , 3, 355-63. PMID: 11710767


Cai J & Ma L. (2011). Msx2 and Foxn1 regulate nail homeostasis. Genesis , 49, 449-59. PMID: 21387539 DOI.

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Search Pubmed: Nail Development | Nail embryology

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Historic Images

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  • Beau lines - nail grooved transverse lines appearing like indentations or ridges in the nail plate. Named in 1846 by Joseph Honoré Simon Beau (1806–1865), a French physician.
  • cuticle - tissue that overlaps the plate and rims the base of the nail
  • hyponychium - the epithelium located beneath the nail plate
  • lunula - half-moon at the base of the nail
  • matrix - hidden part of the nail unit under the cuticle
  • Muehrcke lines - paired transverse white lines appearing in the nails secondary to edematous nail bed, resulting abnormal nail bed vasculature, forming transverse lines that disappear when the nail bed is compressed. Seen in patients with chronic hypoalbuminemia and malnutrition.
  • nail bed - skin beneath the nail plate
  • nail folds - skin folds that frame and support the nail on three sides
  • nail plate - visible part of the nail
  • trachyonychia - nail plate roughness, pitting, and ridging affecting one or all twenty nails.

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Cite this page: Hill, M.A. (2024, February 28) Embryology Integumentary System - Nail Development. Retrieved from

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