Projects and Publications

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1. Using frog faces to understand human orofacial development.

The human orofacial region is our gateway to the world—enabling eating, speaking, and recognition—so defects such as cleft lip and palate are devastating. These are among the most common birth defects, yet their causes remain poorly understood because of the region’s complex and multifactorial development. My lab aims to uncover the developmental and molecular mechanisms driving these anomalies. While most cleft research uses mouse, chick, or zebrafish, Xenopus offers unique advantages: embryos develop externally, the face remains unobscured by head flexure or a beak, and genetic manipulations are rapid and tractable. We were the first to generate an orofacial cleft in Xenopus, establishing a powerful new model to dissect craniofacial development and disease.

Using this platform, we have validated novel human clefting genes and uncovered novel roles for retinoic and folic acid. We are also extending this work to craniofacial defects in Down syndrome, collaborating with Dr. Litovchick to reveal new mechanisms by which DYRK1A shapes face formation. Together, these studies position Xenopus as a transformative model for linking human genetics to developmental mechanisms, with broad implications for understanding and ultimately preventing craniofacial birth defects.

These endeavors have been supported lab by R01DE023553 (NIDCR) and R21HD105144 (NICHD).

 

Relevant Publications:

1. Kennedy, A.E. and A.J. Dickinson, Median facial clefts in Xenopus laevis: roles of retinoic acid signaling and homeobox genes. Dev Biol, 2012. 365(1): p. 229-40. PMID: 22405964

2. Dickinson AJ.  Using frogs faces to dissect the mechanisms underlying human orofacial defects. Semin Cell Dev Biol. 2016 Jan 15. pii: S1084-9521(16)30016-7. PMCID: PMC4798872

3. Brent H. Wyatt, Thomas O. Raymond, Lisa A. Lansdon, Benjamin W. Darbro, Jeffrey C. Murray, J. Robert Manak, A.J.G. Dickinson.  Using an aquatic model, Xenopus laevis, to uncover the role of Chromodomain 1 (CHD1) in craniofacial disorders. Genesis 2020 Sep 11;e23394. doi: 10.1002/dvg.23394.

4. Johnson HK, Litovchick LL, Dickinson AJG. The role of Goldilocks protein kinase DYRK1A in embryonic development. Dev Biol. 2025 Sep;525:216-228. doi: 10.1016/j.ydbio.2025.06.009. Epub 2025 Jun 10.

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2. Pioneering work on determining how the embryonic mouth is formed.

The mouth is the essential gateway to the digestive tract, yet the embryonic events that establish it have been almost entirely overlooked. Until recently, the rupture of the buccopharyngeal membrane, an event that creates the embryonic mouth, was barely mentioned in textbooks and rarely studied in craniofacial biology. This is a critical gap, as we now have evidence that persistent membrane defects may underlie choanal atresia, a malformation seen in nearly 80 craniofacial syndromes. My lab is among the first to tackle this neglected process. We developed a model showing that forces from jaw muscles, combined with local epithelial remodeling, drive perforation of the buccopharyngeal membrane to form the primary mouth. By illuminating how this fundamental opening is created, we are revealing new developmental mechanisms with direct implications for understanding and preventing human craniofacial birth defects. This work was supported by a NSF Career Award  (IOS-1349668)  and R03 RAR065583A (NIAMS).

 

Relevant Publications:

1. Dickinson, A.J. and H. Sive, Development of the primary mouth in Xenopus laevis. Dev Biol, 2006. 295: p.700-13. PMID: 16678148

2. N.S. Houssin, N.K. Bharathan, S.D. Turner, Amanda J.G Dickinson.  The role of JNK during buccopharyngeal membrane perforation, the last step of embryonic mouth formation. Dev Dyn. 2017 Feb;246(2):100-115. PMCID: PMC5261731

3. Bharathan, N. and Dickinson AJG.  Desmoplakin is required for epidermal integrity and morphogenesis in Xenopus. Dev Biol. 2019 Jun 15;450(2):115-131. PMCID: PMC6659752

4. Amanda J. G. Dickinson. Jak2 and Jaw Muscles Are Required for Buccopharyngeal Membrane Perforation during Mouth Development.  J. Dev. Biol. 2023, 11(2), 24. PMCID: PMC10298892

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3. Testing the effects of e-cigarettes and other toxins on craniofacial development

E-cigarettes (ECIGs) are rapidly gaining popularity, especially among youth, with a 78% rise in high school use from 2017 to 2018. Marketed as “safer” and appealing through sweet flavors and sleek designs, their safety remains largely untested—particularly in pregnancy. To address this gap, my lab uses Xenopus as a rapid developmental model. We were the first to show that certain e-liquid flavors cause median clefts, cartilage defects, and reduced craniofacial blood supply—findings highlighted in The Atlantic. More recently, we discovered that vanillin-containing e-liquids disrupt retinoic acid signaling, pointing to a novel gene–environment interaction with direct relevance to craniofacial birth defects. These studies were supported by an R56 RDE026024A (NIDCR).

We are using this same pipeline to investigate other potential toxins such as pesticides and food additives.

Relevant Publications:

1. Kennedy AE, Kandalam S, Olivares-Navarrete R, Dickinson AJG. E-cigarette aerosol exposure can cause craniofacial defects in Xenopus laevis embryos and mammalian neural crest cells. PLoS One. 2017 Sep 28;12(9):e0185729.

2. Amanda J. G. Dickinson1*, Stephen D Turner2,3, Stacey Wahl4, Allyson E Kennedy5, Brent H Wyatt6, Deborah A Pridgen1 E-liquids and vanillin flavoring disrupts retinoic acid signaling and causes craniofacial defects in Xenopus embryos.  Dev Biol. 2021 Sep 17;481:14-29. doi: 10.1016/j.ydbio.2021.09.004. PMID: 34543654  (most experiments and all writing done myself in my lab).

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4. Establishing methods for the analysis of orofacial development in Xenopus

Xenopus laevis has emerged as a powerful model for craniofacial biology, and my lab has pioneered methods to analyze and manipulate facial development in this system. We developed quantitative tools to measure subtle changes in head and face morphology, greatly enhancing the ability to assess gene–environment interactions in craniofacial defects. As a postdoc with Hazel Sive, I co-developed the first Xenopus face transplant technique, enabling region-specific gain and loss of function across all orofacial tissues, something not possible in mammals or zebrafish. My group continues to expand this toolkit, from assays of epidermal mechanics to standardized cranial cartilage measurements, establishing Xenopus as a uniquely tractable system for dissecting the mechanisms of orofacial development.

 

Relevant Publications:

1. Kennedy, A.E. and A.J. Dickinson, Quantification of orofacial phenotypes in Xenopus. J Vis Exp, 2014(93): p. e52062.

2. Kennedy, A.E. and A.J. Dickinson, Quantitative analysis of orofacial development and median clefts in Xenopus laevis. Anat Rec (Hoboken), 2014. 297(5): p. 834-55.

3. Jacox, L.A., A.J. Dickinson, and H. Sive, Facial transplants in Xenopus laevis embryos. J Vis Exp, 2014(85).

4. Desmoplakin is required for epidermal integrity and morphogenesis in Xenopus.  Bharathan, N. and Dickinson AJG.  Dev Biol. 2019 Jun 15;450(2):115-131.

5. In prep- The XenCart Protocol: A Method for Alcian Blue Labeling and Quantitative Analysis of Craniofacial Cartilage in Xenopus

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