Delta-Notch signaling and lateral inhibition in zebrafish spinal cord development.
BACKGROUND
Vertebrate neural development requires precise coordination of cell proliferation and cell specification to guide orderly transition of mitotically active precursor cells into different types of post-mitotic neurons and glia. Lateral inhibition, mediated by the Delta-Notch signaling pathway, may provide a mechanism to regulate proliferation and specification in the vertebrate nervous system. We examined delta and notch gene expression in zebrafish embryos and tested the role of lateral inhibition in spinal cord patterning by ablating cells and genetically disrupting Delta-Notch signaling.


RESULTS
Zebrafish embryos express multiple delta and notch genes throughout the developing nervous system. All or most proliferative precursors appeared to express notch genes whereas subsets of precursors and post-mitotic neurons expressed delta genes. When we ablated identified primary motor neurons soon after they were born, they were replaced, indicating that specified neurons laterally inhibit neighboring precursors. Mutation of a delta gene caused precursor cells of the trunk neural tube to cease dividing prematurely and develop as neurons. Additionally, mutant embryos had excess early specified neurons, with fates appropriate for their normal positions within the neural tube, and a concomitant deficit of late specified cells.


CONCLUSIONS
Our results are consistent with the idea that zebrafish Delta proteins, expressed by newly specified neurons, promote Notch activity in neighboring precursors. This signaling is required to maintain a proliferative precursor population and generate late-born neurons and glia. Thus, Delta-Notch signaling may diversify vertebrate neural cell fates by coordinating cell cycle control and cell specification.
Appel
B
B
Department of Biological Sciences Vanderbilt University Nashville, Tennessee 37235, USA. b.appel@vanderbilt.edu
Givan
L A
LA
Eisen
J S
JS
D000818:Animals; D002454:Cell Differentiation / Q000502:physiology; D005314:Embryonic and Fetal Development / Q000502:physiology; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins / Q000096:biosynthesis / Q000378:metabolism / Q000502:physiology*; D009420:Nervous System / Q000166:cytology / Q000196:embryology; D009474:Neurons / Q000502:physiology; D051881:Receptor, Notch1; D011956:Receptors, Cell Surface; D015398:Signal Transduction / Q000502:physiology*; D013116:Spinal Cord / Q000196:embryology* / Q000502:physiology; D014157:Transcription Factors; D015027:Zebrafish / Q000196:embryology* / Q000502:physiology; D029961:Zebrafish Proteins / Q000502:physiology
D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; C497761:NOTCH1 protein, human; D051881:Receptor, Notch1; D011956:Receptors, Cell Surface; D014157:Transcription Factors; D029961:Zebrafish Proteins; C064045:delta protein