The WNT antagonist cSFRP2 modulates programmed cell death in the developing hindbrain.
In the avian hindbrain, the loss of premigratory neural crest cells from rhombomeres 3 and 5 (r3, r5) through programmed cell death contributes to the patterning of emigrant crest cells into three discrete streams. Programmed cell death is induced by the upregulation of Bmp4 and Msx2 in r3 and r5. We show that cSFRP2, a WNT antagonist, is expressed in the even-numbered rhombomeres and that over-expression of cSfrp2 inhibits Bmp4 expression in r3 and r5, preventing programmed cell death. By contrast, depleting cSFRP2 function in r4 results in elevated levels of Msx2 expression and ectopic programmed cell death, as does overexpression of Wnt1. We propose that programmed cell death in the rhombencephalic neural crest is modulated by pre-patterned cSfrp2 expression and a WNT-BMP signalling loop.
Ellies
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DL
MRC Centre for Developmental Neurobiology, King's College London, Guy's Campus, London, SE1 1UL, UK.
Church
V
V
Francis-West
P
P
Lumsden
A
A
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D001483:Base Sequence; D055415:Bone Morphogenetic Protein 4; D019485:Bone Morphogenetic Proteins / Q000235:genetics / Q000502:physiology; D002642:Chick Embryo; D017931:DNA Primers / Q000235:genetics; D018507:Gene Expression Regulation, Developmental; D017403:In Situ Hybridization; D008959:Models, Neurological; D009432:Neural Crest / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D011506:Proteins / Q000235:genetics / Q000502:physiology*; D011518:Proto-Oncogene Proteins / Q000037:antagonists & inhibitors*; D012249:Rhombencephalon / Q000166:cytology / Q000196:embryology* / Q000378:metabolism*; D051153:Wnt Proteins; D051155:Wnt1 Protein; D029961:Zebrafish Proteins
D055415:Bone Morphogenetic Protein 4; D019485:Bone Morphogenetic Proteins; D017931:DNA Primers; D011506:Proteins; D011518:Proto-Oncogene Proteins; D051153:Wnt Proteins; D051155:Wnt1 Protein; D029961:Zebrafish Proteins; C525813:bmp4 protein, zebrafish