Abstract
Wolf–Hirschhorn syndrome (WHS) is a rare developmental disorder characterized by intellectual disability and various physical malformations including craniofacial, skeletal, and cardiac defects. These phenotypes, as they involve structures that are derived from the cranial neural crest, suggest that WHS may be associated with abnormalities in neural crest cell (NCC) migration. This syndrome is linked with assorted mutations on the short arm of chromosome 4, most notably the microdeletion of a critical genomic region containing several candidate genes. However, the function of these genes during embryonic development, as well as the cellular and molecular mechanisms underlying the disorder, are still unknown. The model organism Xenopus laevis offers a number of advantages for studying WHS. With the Xenopus genome sequenced, genetic manipulation strategies can be readily designed in order to alter the dosage of the WHS candidate genes. Moreover, a variety of assays are available for use in Xenopus to examine how manipulation of WHS genes leads to changes in the development of tissue and organ systems affected in WHS. In this review article, we highlight the benefits of using X. laevis as a model system for studying human genetic disorders of development, with a focus on WHS.
Highlights
Wolf–Hirschhorn syndrome (WHS) is a developmental disorder characterized by craniofacial malformations, intellectual disability, microcephaly, seizures, growth retardation, and developmental delays, though the severity of these symptoms varies from patient to patient (Fisch et al, 2010; Hannes et al, 2010; Sheth et al, 2012; Battaglia et al, 2015; Rutherford and Lowery, 2016)
We provide a brief overview of the known functions of WHS-associated genes and how they may be linked to developmental processes, such as neural crest cell (NCC) migration
We describe the current known functions of the primary WHS candidate genes, as well as other WHS-associated genes, their potential roles during embryonic development, and how they may contribute to the spectrum of WHS phenotypes
Summary
Wolf–Hirschhorn syndrome (WHS) is a developmental disorder characterized by craniofacial malformations, intellectual disability, microcephaly, seizures, growth retardation, and developmental delays, though the severity of these symptoms varies from patient to patient (Fisch et al, 2010; Hannes et al, 2010; Sheth et al, 2012; Battaglia et al, 2015; Rutherford and Lowery, 2016). The link between haploinsufficiency of most WHS-associated genes to specific vertebrate developmental processes such as brain, craniofacial, and heart development, has not been carefully examined. Xenopus is well-suited to examine the role of WHS-associated genes during vertebrate development, and can be used to test whether abnormal NCC migration may be one mechanism by which mutations of these genes contribute to phenotypes of the disease.
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