Meis3 is required for neural crest invasion of the gut during zebrafish enteric nervous system development.
During development, vagal neural crest cells fated to contribute to the enteric nervous system migrate ventrally away from the neural tube toward and along the primitive gut. The molecular mechanisms that regulate their early migration en route to and entry into the gut remain elusive. Here we show that the transcription factor meis3 is expressed along vagal neural crest pathways. Meis3 loss of function results in a reduction in migration efficiency, cell number, and the mitotic activity of neural crest cells in the vicinity of the gut but has no effect on neural crest or gut specification. Later, during enteric nervous system differentiation, Meis3-depleted embryos exhibit colonic aganglionosis, a disorder in which the hindgut is devoid of neurons. Accordingly, the expression of Shh pathway components, previously shown to have a role in the etiology of Hirschsprung's disease, was misregulated within the gut after loss of Meis3. Taken together, these findings support a model in which Meis3 is required for neural crest proliferation, migration into, and colonization of the gut such that its loss leads to severe defects in enteric nervous system development.
Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125.
Rosa A
RA
Uribe
Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125 mbronner@caltech.edu.
Marianne E
ME
Bronner
D000818:Animals; D002454:Cell Differentiation / Q000502:physiology; D017615:Enteric Nervous System / Q000196:embryology* / Q000378:metabolism*; D018398:Homeodomain Proteins / Q000378:metabolism*; D009432:Neural Crest / Q000196:embryology* / Q000378:metabolism*; D009474:Neurons; D038081:Organogenesis; D015027:Zebrafish; D029961:Zebrafish Proteins / Q000378:metabolism*
D018398:Homeodomain Proteins; C102642:Meis3 protein, zebrafish; D029961:Zebrafish Proteins