Abstract
Genes of the Eya family and of the Six1/2 subfamily are expressed throughout development of vertebrate cranial placodes and are required for their differentiation into ganglia and sense organs. How they regulate placodal neurogenesis, however, remains unclear. Through loss of function studies in Xenopus we show that Eya1 and Six1 are required for neuronal differentiation in all neurogenic placodes. The effects of overexpression of Eya1 or Six1 are dose dependent. At higher levels, Eya1 and Six1 expand the expression of SoxB1 genes (Sox2, Sox3), maintain cells in a proliferative state and block expression of neuronal determination and differentiation genes. At lower levels, Eya1 and Six1 promote neuronal differentiation, acting downstream of and/or parallel to Ngnr1. Our findings suggest that Eya1 and Six1 are required for both the regulation of placodal neuronal progenitor proliferation, through their effects on SoxB1 expression, and subsequent neuronal differentiation.
Publication types
-
Research Support, N.I.H., Extramural
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Animals
-
Biomarkers / metabolism
-
Cell Differentiation* / drug effects
-
Cell Proliferation / drug effects
-
DNA-Binding Proteins / metabolism*
-
Ectoderm / cytology
-
Ectoderm / drug effects
-
Embryo, Nonmammalian / cytology
-
Embryo, Nonmammalian / drug effects
-
Gene Expression Regulation, Developmental / drug effects
-
High Mobility Group Proteins / metabolism*
-
Homeodomain Proteins / metabolism*
-
Humans
-
Injections
-
Intracellular Signaling Peptides and Proteins / metabolism*
-
Models, Biological
-
Neurons / cytology*
-
Neurons / drug effects
-
Nuclear Proteins / metabolism*
-
Oligonucleotides, Antisense / pharmacology
-
Protein Tyrosine Phosphatases / metabolism*
-
Receptors, Glucocorticoid / metabolism
-
Recombinant Fusion Proteins / metabolism
-
SOXB1 Transcription Factors
-
Skull / drug effects
-
Skull / embryology*
-
Stem Cells / cytology
-
Stem Cells / drug effects
-
Transcription Factors / metabolism*
-
Xenopus / embryology*
-
Xenopus Proteins / metabolism*
Substances
-
Biomarkers
-
DNA-Binding Proteins
-
High Mobility Group Proteins
-
Homeodomain Proteins
-
Intracellular Signaling Peptides and Proteins
-
Nuclear Proteins
-
Oligonucleotides, Antisense
-
Receptors, Glucocorticoid
-
Recombinant Fusion Proteins
-
SOX3 protein, human
-
SOXB1 Transcription Factors
-
Six1 protein, Xenopus
-
Sox3 protein, Xenopus
-
Transcription Factors
-
Xenopus Proteins
-
Eya1 protein, Xenopus
-
Protein Tyrosine Phosphatases