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Homeobox gene Nkx2.2 and specification of neuronal identity by graded Sonic hedgehog signalling.
- Source :
-
Nature [Nature] 1999 Apr 15; Vol. 398 (6728), pp. 622-7. - Publication Year :
- 1999
-
Abstract
- During vertebrate development, the specification of distinct cell types is thought to be controlled by inductive signals acting at different concentration thresholds. The degree of receptor activation in response to these signals is a known determinant of cell fate, but the later steps at which graded signals are converted into all-or-none distinctions in cell identity remain poorly resolved. In the ventral neural tube, motor neuron and interneuron generation depends on the graded activity of the signalling protein Sonic hedgehog (Shh). These neuronal subtypes derive from distinct progenitor cell populations that express the homeodomain proteins Nkx2.2 or Pax6 in response to graded Shh signalling. In mice lacking Pax6, progenitor cells generate neurons characteristic of exposure to greater Shh activity. However, Nkx2.2 expression expands dosally in Pax6 mutants, raising the possibility that Pax6 controls neuronal pattern indirectly. Here we provide evidence that Nkx2.2 has a primary role in ventral neuronal patterning. In Nkx2.2 mutants, Pax6 expression is unchanged but cells undergo a ventral-to-dorsal transformation in fate and generate motor neurons rather than interneurons. Thus, Nkx2.2 has an essential role in interpreting graded Shh signals and selecting neuronal identity.
- Subjects :
- Animals
Body Patterning physiology
Cell Lineage genetics
Cell Lineage physiology
Culture Techniques
DNA-Binding Proteins physiology
Embryonic Induction
Eye Proteins
Hedgehog Proteins
Homeobox Protein Nkx-2.2
Homeodomain Proteins genetics
Interneurons cytology
Mice
Motor Neurons cytology
Mutation
PAX6 Transcription Factor
Paired Box Transcription Factors
Repressor Proteins
Rhombencephalon cytology
Rhombencephalon embryology
Spinal Cord cytology
Spinal Cord embryology
Transcription Factors genetics
Zebrafish Proteins
Genes, Homeobox
Homeodomain Proteins physiology
Neurons cytology
Proteins physiology
Signal Transduction
Trans-Activators
Transcription Factors physiology
Subjects
Details
- Language :
- English
- ISSN :
- 0028-0836
- Volume :
- 398
- Issue :
- 6728
- Database :
- MEDLINE
- Journal :
- Nature
- Publication Type :
- Academic Journal
- Accession number :
- 10217145
- Full Text :
- https://doi.org/10.1038/19315