Microarray identification of novel genes downstream of Six1, a critical factor in cranial placode, somite, and kidney development

• Published in: Developmental dynamics 2015-02, Vol.244 (2), p.181-210
• Main Authors: Yan, Bo, Neilson, Karen M., Ranganathan, Ramya, Maynard, Thomas, Streit, Andrea, Moody, Sally A.
• Format: Article
• Language: English
• Subjects: Animals; BOR syndrome; BOS syndrome; cranial ganglia; Gene Expression Profiling; Gene Expression Regulation, Developmental - physiology; Homeodomain Proteins - genetics; Homeodomain Proteins - metabolism; Kidney - cytology; Kidney - embryology; olfactory; Oligonucleotide Array Sequence Analysis; otocyst; pan‐placodal region; preplacodal ectoderm; Skull - cytology; Skull - embryology; Somites - cytology; Somites - embryology; Xenopus; Xenopus laevis; Xenopus Proteins - genetics; Xenopus Proteins - metabolism
• ISSN: 1058-8388; 1097-0177
• DOI: 10.1002/dvdy.24229

Background: Six1 plays an important role in the development of several vertebrate organs, including cranial sensory placodes, somites, and kidney. Although Six1 mutations cause one form of branchio‐otic syndrome (BOS), the responsible gene in many patients has not been identified; genes that act downstream of Six1 are potential BOS candidates. Results: We sought to identify novel genes expressed during placode, somite and kidney development by comparing gene expression between control and Six1‐expressing ectodermal explants. The expression patterns of 19 of the significantly up‐regulated and 11 of the significantly down‐regulated genes were assayed from cleavage to larval stages. A total of 28/30 genes are expressed in the otocyst, a structure that is functionally disrupted in BOS, and 26/30 genes are expressed in the nephric mesoderm, a structure that is functionally disrupted in the related branchio‐otic‐renal (BOR) syndrome. We also identified the chick homologues of five genes and show that they have conserved expression patterns. Conclusions: Of the 30 genes selected for expression analyses, all are expressed at many of the developmental times and appropriate tissues to be regulated by Six1. Many have the potential to play a role in the disruption of hearing and kidney function seen in BOS/BOR patients. Developmental Dynamics 244:181–210, 2015. © 2014 Wiley Periodicals, Inc. Key Findings To identify potential causative genes for BOS and BOR, we used a microarray approach to generate a more complete list of genes likely to be regulated by the Six1 transcription factor. We describe the expression patterns of 30 genes that were significantly different between Six1‐expressing and control data sets, most of which have not been previously characterized in Xenopus. 28/30 genes are expressed in the otocyst, a structure that is functionally disrupted in Branchio‐otic Syndrome. 26/30 genes are expressed in the nephric mesoderm, a structure that is functionally disrupted in the related Branchio‐Otic‐Renal Syndrome. We also identified the chick homologues of 5 genes and show that they have conserved expression patterns.