Developmental Biology: Shaping the sound of voice
The proper development of the vocal cords requires embryos to contain a certain number of progenitor cells, and mutations that lead to an overflow of cells can cause malformations of the voice box.
- University of California San Francisco, United States
Acoustic communication is used by many different species. Animals employ sound to attract mates, to sense their environment, to send messages, to convey danger or just to entertain, while insects like ants and crickets also use sound for communication. There is even evidence that some plants use ‘acoustic reflectors’ to attract bats to pollinate, fertilize and distribute seeds (Schoner et al., 2016).
Vertebrates have many different ways to produce sound. Birds sing via a syrinx, for example, while dolphins emit ultrasonic waves by passing air through a structure called the dorsal bursa. Other mammals rely on a complex structure called the larynx that houses the vocal cords and is made of cartilage, muscle, ligament and connective tissue. As the air flows through the larynx, the shape and tension of the vocal cords create sounds through vibration, while the cartilage manipulates the pitch.
Although the biology of language and speech has been studied for decades, our understanding of how the vocal organs develop is still patchy, and most of what we know about the development of the larynx is based on research in bird embryos (Evans and Noden, 2006). As an embryo develops, the cells that will become the vocal organs undergo a series of transformations that are orchestrated by various signaling factors and pathways. Mutations in these pathways can cause structural birth defects, and such mutations may also lead to characteristic vocal traits in humans. For instance, patients with Pallister-Hall Syndrome (Hall et al., 1980), which arises from mutations in a Hedgehog signaling protein called Gli3, are said to have ‘growling’ voices.
Hedgehog signaling occurs within cellular structures called cilia, and patients with mutations in ciliary proteins also suffer from defects in their voice (Beales et al., 1999). It is also known that a ciliary protein called Fuz is required for Gli3 processing (Adler and Wallingford, 2017) but, until recently, it was not known if there was a mechanistic link between disorders affecting the cilia and the development of the larynx. Now, in eLife, John Wallingford and colleagues – including Jacqueline Tabler and Maggie Rigney of the University of Texas at Austin as joint first authors – report that Fuz is essential for the development of the larynx (Tabler et al., 2017).
To better understand how molecular signals and proteins regulate the development of the larynx, Tabler et al. used mutant mice that lacked either Gli3 or Fuz. In both groups of mice, the formation of the larynx was disrupted, but more severely in mice without Fuz. Tabler et al. then looked more closely at proteins of the Hedgehog signaling pathway, which are affected in Fuz mutants. In particular, they focused on a specific type of mutation in the gene for Gli3 that is known to cause birth defects in humans. Indeed, the larynx did not develop properly in these mice because of a build-up of connective tissue near the vocal cords, which affected their ability to make a sound.
In addition, an acoustic map comparing the sounds from wild type and Gli3 mutant mice showed that sound production was negatively affected in the mutants. It appears that changes to the sounds produced are not caused by changes in brain activity, but by physical changes in the larynx itself.
Lying at the heart of the complex process of laryngeal formation and malformation in these mutants is an incredibly simple explanation. Mutant embryos had more progenitor cells – the cells that are destined to build the larynx but have not fully developed yet. Tabler et al. suggest that regulation of the number of progenitor cells could have a role in many disorders affecting the cilia. This is not surprising as the size of the pool of progenitor cells is known to have an important role in other diseases (Jones et al., 2008) and also in evolution (Fish et al., 2014). Some of the observed changes have also been found in other animals, suggesting a conceptual framework for exploring the molecular and developmental basis of evolution that may contribute to diversity of the vocal repertoire among vertebrates.
References
-
New criteria for improved diagnosis of Bardet-Biedl syndrome: results of a population surveyJournal of Medical Genetics 36:437–446.
-
Spatial relations between avian craniofacial neural crest and paraxial mesoderm cellsDevelopmental Dynamics 235:1310–1325.https://doi.org/10.1002/dvdy.20663
-
Acoustic communication in plant-animal interactionsCurrent Opinion in Plant Biology 32:88–95.https://doi.org/10.1016/j.pbi.2016.06.011
Article and author information
Author details
Publication history
Copyright
© 2017, Marcucio
This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited.
Metrics
-
- 1,067
- views
-
- 94
- downloads
-
- 0
- citations
Views, downloads and citations are aggregated across all versions of this paper published by eLife.
Download links
A two-part list of links to download the article, or parts of the article, in various formats.
Downloads (link to download the article as PDF)
Open citations (links to open the citations from this article in various online reference manager services)
Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)
Developmental Biology: Shaping the sound of voice
eLife 6:e25858.
https://doi.org/10.7554/eLife.25858
Further reading
-
- Developmental Biology
Hair follicle development is initiated by reciprocal molecular interactions between the placode-forming epithelium and the underlying mesenchyme. Cell fate transformation in dermal fibroblasts generates a cell niche for placode induction by activation of signaling pathways WNT, EDA, and FGF in the epithelium. These successive paracrine epithelial signals initiate dermal condensation in the underlying mesenchyme. Although epithelial signaling from the placode to mesenchyme is better described, little is known about primary mesenchymal signals resulting in placode induction. Using genetic approach in mice, we show that Meis2 expression in cells derived from the neural crest is critical for whisker formation and also for branching of trigeminal nerves. While whisker formation is independent of the trigeminal sensory innervation, MEIS2 in mesenchymal dermal cells orchestrates the initial steps of epithelial placode formation and subsequent dermal condensation. MEIS2 regulates the expression of transcription factor Foxd1, which is typical of pre-dermal condensation. However, deletion of Foxd1 does not affect whisker development. Overall, our data suggest an early role of mesenchymal MEIS2 during whisker formation and provide evidence that whiskers can normally develop in the absence of sensory innervation or Foxd1 expression.
-
- Developmental Biology
The evolutionarily conserved Hippo (Hpo) pathway has been shown to impact early development and tumorigenesis by governing cell proliferation and apoptosis. However, its post-developmental roles are relatively unexplored. Here, we demonstrate its roles in post-mitotic cells by showing that defective Hpo signaling accelerates age-associated structural and functional decline of neurons in Caenorhabditis elegans. Loss of wts-1/LATS, the core kinase of the Hpo pathway, resulted in premature deformation of touch neurons and impaired touch responses in a yap-1/YAP-dependent manner, the downstream transcriptional co-activator of LATS. Decreased movement as well as microtubule destabilization by treatment with colchicine or disruption of microtubule-stabilizing genes alleviated the neuronal deformation of wts-1 mutants. Colchicine exerted neuroprotective effects even during normal aging. In addition, the deficiency of a microtubule-severing enzyme spas-1 also led to precocious structural deformation. These results consistently suggest that hyper-stabilized microtubules in both wts-1-deficient neurons and normally aged neurons are detrimental to the maintenance of neuronal structural integrity. In summary, Hpo pathway governs the structural and functional maintenance of differentiated neurons by modulating microtubule stability, raising the possibility that the microtubule stability of fully developed neurons could be a promising target to delay neuronal aging. Our study provides potential therapeutic approaches to combat age- or disease-related neurodegeneration.
