The Role of Goldilocks Protein Kinase DYRK1A in Embryonic Development

DYRK1A (Dual-specificity Tyrosine (Y) Regulated Kinase) is a dosage sensitive gene where too much or too little of its “Goldilocks” protein product can result in structural birth defects. DYRK1A loss of function variants are associated with DYRK1A syndrome, which is characterized by intellectual disability and stereotypical craniofacial anomalies. DYRK1A is located on chromosome 21 and increased dosage of this gene as a result of Trisomy 21 is thought to be an important contributor to a range of developmental anomalies and comorbidities associated with Down syndrome. Animal models have revealed that too little or too much of this protein can have significant multiorgan effects on the developing embryo. Moreover, in Down syndrome mouse models, normalizing Dyrk1a can improve some aspects of the birth defects associated with this disease. This review emphasizes that a thorough understanding of the effects of the DYRK1A imbalance on embryonic development can lead to important insights into DYRK1A associated syndromes and inform the development of prevention and treatment strategies for these birth defects.