Microarray identification of novel genes downstream of Six1, a critical factor in cranial placode, somite, and kidney development.
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.
Department of Anatomy and Regenerative Biology, The George Washington University, School of Medicine and Health Sciences, Washington, DC.
Bo
B
Yan
Karen M
KM
Neilson
Ramya
R
Ranganathan
Thomas
T
Maynard
Andrea
A
Streit
Sally A
SA
Moody
D000818:Animals; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D007668:Kidney / Q000166:cytology / Q000196:embryology*; D020411:Oligonucleotide Array Sequence Analysis; D012886:Skull / Q000166:cytology / Q000196:embryology*; D019170:Somites / Q000166:cytology / Q000196:embryology*; D029867:Xenopus Proteins / Q000235:genetics / Q000378:metabolism*; D014982:Xenopus laevis
D018398:Homeodomain Proteins; C530879:Six1 protein, Xenopus; D029867:Xenopus Proteins
BOR syndrome; BOS syndrome; cranial ganglia; olfactory; otocyst; pan-placodal region; preplacodal ectoderm