The receptor tyrosine kinase RET regulates hindgut colonization by sacral neural crest cells.
The enteric nervous system (ENS) is formed from vagal and sacral neural crest cells (NCC). Vagal NCC give rise to most of the ENS along the entire gut, whereas the contribution of sacral NCC is mainly limited to the hindgut. This, and data from heterotopic quail-chick grafting studies, suggests that vagal and sacral NCC have intrinsic differences in their ability to colonize the gut, and/or to respond to signalling cues within the gut environment. To better understand the molecular basis of these differences, we studied the expression of genes known to be essential for ENS formation, in sacral NCC within the chick hindgut. Our results demonstrate that, as in vagal NCC, Sox10, EdnrB, and Ret are expressed in sacral NCC within the gut. Since we did not detect a qualitative difference in expression of these ENS genes we performed DNA microarray analysis of vagal and sacral NCC. Of 11 key ENS genes examined from the total data set, Ret was the only gene identified as being highly differentially expressed, with a fourfold increase in expression in vagal versus sacral NCC. We also found that over-expression of RET in sacral NCC increased their ENS developmental potential such that larger numbers of cells entered the gut earlier in development, thus promoting the fate of sacral NCC towards that of vagal NCC.
Delalande
Jean-Marie
JM
Neural Development Unit, UCL Institute of Child Health, 30 Guilford Street, London, WC1N 1EH, UK.
Barlow
Amanda J
AJ
Thomas
Aaron J
AJ
Wallace
Adam S
AS
Thapar
Nikhil
N
Erickson
Carol A
CA
Burns
Alan J
AJ
D000818:Animals; D002465:Cell Movement; D002642:Chick Embryo; D004268:DNA-Binding Proteins / Q000378:metabolism; D004064:Digestive System / Q000196:embryology / Q000294:innervation / Q000378:metabolism; D004625:Embryo, Nonmammalian / Q000378:metabolism; D017615:Enteric Nervous System / Q000196:embryology* / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D006609:High Mobility Group Proteins / Q000378:metabolism; D009432:Neural Crest / Q000166:cytology* / Q000637:transplantation; D020411:Oligonucleotide Array Sequence Analysis; D051096:Proto-Oncogene Proteins c-ret / Q000378:metabolism*; D011784:Quail; D055757:SOXE Transcription Factors; D012447:Sacrum / Q000166:cytology; D014157:Transcription Factors / Q000378:metabolism; D014183:Transplantation, Heterologous
D004268:DNA-Binding Proteins; D006609:High Mobility Group Proteins; D055757:SOXE Transcription Factors; D014157:Transcription Factors; D051096:Proto-Oncogene Proteins c-ret