Engrailed-1 and Netrin-1 regulate axon pathfinding by association interneurons that project to motor neurons
Autor: | Martyn Goulding, Harald Saueressig, John D. Burrill |
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Rok vydání: | 1999 |
Předmět: |
Time Factors
Interneuron Population Biology Mice Pioneer axon Interneurons Netrin medicine Animals Nerve Growth Factors education Molecular Biology Homeodomain Proteins Motor Neurons Spinal interneuron education.field_of_study Microscopy Confocal Chemotactic Factors Models Genetic Histocytochemistry Tumor Suppressor Proteins Gene Expression Regulation Developmental Cell Differentiation Anatomy Netrin-1 Spinal cord Axons Phenotype medicine.anatomical_structure Spinal Cord nervous system Mutagenesis GDF7 Axon guidance Neuroscience Transcription Factors Developmental Biology |
Zdroj: | Development. 126:4201-4212 |
ISSN: | 1477-9129 0950-1991 |
DOI: | 10.1242/dev.126.19.4201 |
Popis: | During early development, multiple classes of interneurons are generated in the spinal cord including association interneurons that synapse with motor neurons and regulate their activity. Very little is known about the molecular mechanisms that generate these interneuron cell types, nor is it known how axons from association interneurons are guided toward somatic motor neurons. By targeting the axonal reporter gene tau-lacZ to the En1 locus, we show the cell-type-specific transcription factor Engrailed-1 (EN1) defines a population of association neurons that project locally to somatic motor neurons. These EN1 interneurons are born early and their axons pioneer an ipsilateral longitudinal projection in the ventral spinal cord. The EN1 interneurons extend axons in a stereotypic manner, first ventrally, then rostrally for one to two segments where their axons terminate close to motor neurons. We show that the growth of EN1 axons along a ventrolateral pathway toward motor neurons is dependent on netrin-1 signaling. In addition, we demonstrate that En1 regulates pathfinding and fasciculation during the second phase of EN1 axon growth in the ventrolateral funiculus (VLF); however, En1 is not required for the early specification of ventral interneuron cell types in the embryonic spinal cord. |
Databáze: | OpenAIRE |
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