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

Dev Dyn. 2015 Feb;244(2):181-210. doi: 10.1002/dvdy.24229. Epub 2014 Dec 16.

Abstract

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.

Keywords: BOR syndrome; BOS syndrome; cranial ganglia; olfactory; otocyst; pan-placodal region; preplacodal ectoderm.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Gene Expression Profiling
  • Gene Expression Regulation, Developmental / physiology*
  • Homeodomain Proteins / genetics
  • Homeodomain Proteins / metabolism*
  • Kidney / cytology
  • Kidney / embryology*
  • Oligonucleotide Array Sequence Analysis
  • Skull / cytology
  • Skull / embryology*
  • Somites / cytology
  • Somites / embryology*
  • Xenopus Proteins / genetics
  • Xenopus Proteins / metabolism*
  • Xenopus laevis

Substances

  • Homeodomain Proteins
  • Six1 protein, Xenopus
  • Xenopus Proteins