Embryology, Lanugo


Article Author:
Brendon Verhave


Article Editor:
Sarah Lappin


Editors In Chief:
Amanda Oakley
Jules Lipoff
Shyam Verma


Managing Editors:
Orawan Chaigasame
Carrie Smith
Abdul Waheed
Frank Smeeks
Kristina Soman-Faulkner
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Radia Jamil
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Saad Nazir
William Gossman
Pritesh Sheth
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Navid Mahabadi
Steve Bhimji
John Shell
Matthew Varacallo
Ahmad Malik
Mark Pellegrini
James Hughes
Beata Beatty
Hajira Basit
Phillip Hynes


Updated:
10/27/2018 12:32:07 PM

Introduction

Languo is fine, soft, unpigmented hair that is often present in fetuses, newborns, and in certain disease states, for example, anorexia. While lanugo is a normal finding in fetuses, its presence becomes more indicative of pathology in an older person than in a younger person, for example, lanugo in a 20-year-old is more worrisome than lanugo in a neonate. Many different cell types and molecular mechanisms contribute to the development of lanugo. It is an important tissue type necessary to ensure normal fetal development.

Development

Lanugo plays an important role in binding the vernix caseosa to the skin of fetuses. The vernix caseosa is (the viscous white covering on newborns that protects their skin, prevents water loss, plays an important role in thermoregulation, and contributes to innate immunity. This protects the fetus from damaging substances found in amniotic fluid, most notably urea and electrolytes. Lanugo is the first type of hair to develop in humans. Lanugo’s interaction with the vernix is also important in controlling the tempo of the fetal developmental rate during various times in the gestation cycle. Lanugo arises at about 3 months into development. Hair growth starts on the scalp (around the eyebrow, nose, and forehead area) and proceeds in a cephalocaudal direction (from head to toe). It is shed at about 33 to 36 weeks gestation, when it is subsequently incorporated into the amniotic fluid, eventually contributing to the composition of the meconium. Lanugo is ultimately replaced by villus (fine, thin hair) and terminal hair (thicker hairs found on the scalp, axilla, and genitalia). Often, lanugo is still present on the neonate (found in up to 30% of newborns). This is a normal finding.

If lanugo is present at birth, it is usually a benign physical exam finding.  After the vernix is removed, small amounts of lanugo can remain on the neonate temporarily. Lanugo can thus be present on the neonate for the first few weeks of life. Its presence can, however, indicate premature birth in a minority of cases. When present in an adult, lanugo can be a sign of serious underlying disease states. These include, most notably, anorexia, bulimia, various forms of malnutrition, and the presence of a teratoma.[1]

Cellular

Lanugo, like all types of hair, is derived from the ectoderm. The cell types present in the hair follicle of lanugo hair include: hair follicle stem cells (present in the bulge and matrix of the hair follicle), germinal matrix cells (form the hair shaft), mesenchymal cells (form the hair papilla), keratinocytes (form keratin in the epidermis), and fibroblasts (form collagen). While about 20 different cell types comprise the hair follicle of a lanugo hair, the cells above are the most relevant to clinical practice.

Biochemical

Many biochemical processes involve signal relays from the dermal papilla to the hair follicle occur to form lanugo hair. This results in the activation of downstream signaling pathways and the activation of transcription factors.

Molecular

Sonic hedgehog pathway and its effectors are key to lanugo development (and another type of hair development as well).  Antagonists of Wnt and its effectors are also important. While other mediators are necessary for the eventual production of lanugo, these 2 are the most relevant. In either case, molecular messages beginning the process of hair development begin in the dermis. In the absence of a Wnt signal, cytoplasmic beta-catenin is phosphorylated and targeted for destruction by a protein complex. This complex includes axin, adenomatous polyposis coli tumor suppressor protein (APC) and glycogen synthase 3-beta (GSK3-beta). In the presence of an antagonistic Wnt signal, the degradation complex is inhibited and beta-catenin moves to the nucleus. There it forms a transcription complex with DNA binding factors of the lymphoid enhancer-binding factor/T cell factor family. This then activates transcription of various target genes. In the absence of an SHH signal, the actions of the Patched-1 (PTC1) SHH receptor inhibit the activity of the smoothened (Smo) protein. In the presence of SHH, the repression of Smo is removed, and target genes, including PTC1 and GLI1, are transcribed through the actions of the transcription factors GLI1 and GLI2.  After further downstream processes, the formation of lanugo and other types of hair is achieved.[2]

Function

Lanugo plays a vital role in binding the vernix to the skin. This protects the fetus from damaging substances found in amniotic fluid.  Lanugo’s interaction with the vernix also results in an increased rate of fetal growth during development (mid-gestation) and a decreased rate of fetal growth at the end of gestation.

Mechanism

Lanugo fulfills its role via serving as a physical anchor between the skin and vernix. Lanugo imparts an increased surface area to the fetus, allowing more interactions between itself and the vernix (and thus a stronger anchor). Without lanugo, the vernix would not stay affixed to the skin and therefore would not be able to protect the fetus from harmful substances in the environment.

Regarding regulating fetal developmental rate, oscillations of lanugo hairs surrounded by the vernix during fetal movements in amniotic fluid activate sensitive mechanoreceptors connected to unmyelinated C-afferent fibers. These afferents function to relay impulses originating from all fetal skin dermatomes via the spinal cord and activate the vagal sensory zone, hypothalamus, and insular cortex. This results in the promotion of an "anti-stress" effect through oxytocin release. This also results in the stimulation of fetal growth by the incretin effect of various gastrointestinal hormones.

Testing

Lanugo is detected on physical exam. It is fine, thin, very soft, and depigmented hair. If it is suspected that lanugo is due to other diseases, a more thorough systemic workup should be completed. This includes psychiatric evaluation (for anorexia and bulimia), complete blood count (CBC), complete metabolic panel (CMP), and the search for other tumor markers, for example, concern for teratoma. The degree of lanugo presence and its distribution should be noted as well, as this can correlate with disease severity.

Pathophysiology

In disease states, such as malnutrition and anorexia where thermoregulation becomes disrupted, lanugo grows in adults to help insulate the body (it is a natural response to an unnatural insult, in other words, lack of thermoregulation). Molecular signals from the dermal papilla are released following the detection of temperature dysregulation and cause a series of signaling events (mostly via Smo, PTCH, and other SHH components) leading to the ultimate formation of lanugo hair.

Clinical Significance

If lanugo is recognized in a newborn, suspicion for prematurity should be raised, however, this is more often a normal variant than not. When lanugo is present in an adult, this is a “red flag,” and an underlying systemic disease should be considered and ruled out.


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Embryology, Lanugo - Questions

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In which of the following periods does the primary hair germ develop in utero?



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Lanugo covers the body and head when the fetus is about _______ months:



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A neonate is born without vernix. It is later noted that the baby lacks any fine, depigmented hairs as well. Which of the following is most likely to be increased in activity in this neonate?



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At 38 weeks gestation, the fetus of a G1P0 28-year-old woman is noted to have accelerated growth of its head and body. If this is a consequence of abnormal lanugo development, which of the following is also most likely to be functioning improperly?



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Which of the following is not a cell type involved in the development of lanugo hair?



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Embryology, Lanugo - References

References

Ahmed YA,Ali S,Ghallab A, Hair histology as a tool for forensic identification of some domestic animal species. EXCLI journal. 2018     [PubMed]
Zhou L,Wang H,Jing J,Yu L,Wu X,Lu Z, Regulation of hair follicle development by exosomes derived from dermal papilla cells. Biochemical and biophysical research communications. 2018 Jun 2     [PubMed]

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