Active Suppression of Interneuron Programs within Developing Motor Neurons Revealed by Analysis of Homeodomain Factor HB9

@article{Thaler1999ActiveSO,
  title={Active Suppression of Interneuron Programs within Developing Motor Neurons Revealed by Analysis of Homeodomain Factor HB9},
  author={J. Thaler and K. Harrison and K. Sharma and Karen Lettieri and J. Kehrl and S. Pfaff},
  journal={Neuron},
  year={1999},
  volume={23},
  pages={675-687}
}
Sonic hedgehog (Shh) specifies the identity of both motor neurons (MNs) and interneurons with morphogen-like activity. Here, we present evidence that the homeodomain factor HB9 is critical for distinguishing MN and interneuron identity in the mouse. Presumptive MN progenitors and postmitotic MNs express HB9, whereas interneurons never express this factor. This pattern resembles a composite of the avian homologs MNR2 and HB9. In mice lacking Hb9, the genetic profile of MNs is significantly… Expand
Different Levels of Repressor Activity Assign Redundant and Specific Roles to Nkx6 Genes in Motor Neuron and Interneuron Specification
TLDR
A reduction in Nkx6 activity further permits V0 neurons to be generated from progenitors that lack homeodomain proteins normally required for their generation, providing direct evidence for a model in which progenitor homeodOMain proteins direct specific cell fates by actively suppressing the expression of transcription factors that direct alternative fates. Expand
Control of hindbrain motor neuron differentiation by the homeobox gene Phox2b.
TLDR
Genetic evidence is provided that the paired-like homeodomain protein Phox2b is required for the formation of all branchial and visceral, but not somatic, motor neurons in the hindbrain, which exemplifies a novel control point in the generation of CNS neurons. Expand
LIM Factor Lhx3 Contributes to the Specification of Motor Neuron and Interneuron Identity through Cell-Type-Specific Protein-Protein Interactions
TLDR
Using in vivo function and protein interaction assays, it is found that Lhx3 binds directly to the LIM cofactor NLI to trigger V2 interneuron differentiation in motor neurons, enabling specific LIM complexes to form in each cell type and ensures that neuronal fates are tightly segregated. Expand
Ventral neural patterning by Nkx homeobox genes: Nkx6.1 controls somatic motor neuron and ventral interneuron fates.
TLDR
The patterns of neurogenesis in mice carrying a targeted mutation in Nkx6.1 show a dorsal-to-ventral switch in the identity of progenitors and in the fate of postmitotic neurons, demonstrating the essential functions of NkX6. Expand
Pax6 regulates specification of ventral neurone subtypes in the hindbrain by establishing progenitor domains.
TLDR
Pax6 regulates specification of the ventral neurone subtypes by establishing the correct progenitor domains by regulating the expression patterns of HD protein genes and subtype-specific neuronal markers in the hindbrain of the Pax6 homozygous mutant rat. Expand
Regulation of motor neuron subtype identity by repressor activity of Mnx class homeodomain proteins
TLDR
It is shown that MNR2 expression persists in postmitotic motor neurons that populate the median motor column, whereas its expression is rapidly extinguished from lateral motor column neurons and from preganglionic autonomic neurons of the Column of Terni (CT). Expand
Chx10 Consolidates V2a Interneuron Identity through Two Distinct Gene Repression Modes.
TLDR
This study uncovers a widely applicable gene regulatory principle for segregating related cell fates, and demonstrates that the paired homeodomain factor Chx10 functions as a critical determinant for V2a fate and is required to consolidate V 2a identity in postmitotic neurons. Expand
Drosophila homeodomain protein Nkx6 coordinates motoneuron subtype identity and axonogenesis
TLDR
It is demonstrated that homeodomain protein Nkx6 is a key member of the genetic network of transcription factors that specifies neuronal fates in Drosophila to link neuronal subtype identity to neuronal morphology and connectivity. Expand
Combinatorial Roles of Olig2 and Neurogenin2 in the Coordinated Induction of Pan-Neuronal and Subtype-Specific Properties of Motoneurons
TLDR
Basic helix-loop-helix (bHLH) transcription factors Olig2 and Neurogenin2 (Ngn2) play vital roles in the coordinated induction of pan-neuronal and subtype-specific properties of motoneurons. Expand
Suppression of interneuron programs and maintenance of selected spinal motor neuron fates by the transcription factor AML1/Runx1
TLDR
These findings show an important role for Runx1 during the consolidation of selected spinal motor neuron identities and suggest a requirement for a persistent suppression of interneuron genes within maturing motor neurons. Expand
...
1
2
3
4
5
...

References

SHOWING 1-10 OF 103 REFERENCES
Requirement for the Homeobox Gene Hb9 in the Consolidation of Motor Neuron Identity
TLDR
Findings show that HB9 has an essential function in consolidating the identity of postmitotic MNs, and in mice lacking Hb9 function, MNs are generated on schedule and in normal numbers but transiently acquire molecular features of V2 interneurons. Expand
Specification of Motor Neuron Identity by the MNR2 Homeodomain Protein
TLDR
The results suggest that the Shh-mediated induction of a single transcription factor, MNR2, is sufficient to direct somatic motor neuron differentiation. Expand
Requirement for LIM Homeobox Gene Isl1 in Motor Neuron Generation Reveals a Motor Neuron– Dependent Step in Interneuron Differentiation
TLDR
Cell differentiation in the neural tube of embryos in which ISL1 expression has been eliminated by gene targeting shows that ISl1 is required for the generation of motor neurons and suggests that motor neuron generation is requiredfor the subsequent differentiation of certain interneurons. Expand
LIM Homeodomain Factors Lhx3 and Lhx4 Assign Subtype Identities for Motor Neurons
TLDR
Lhx3 and Lhx4 act in a binary fashion during a brief period in development to specify the trajectory of motor axons from the neural tube. Expand
Homeobox gene Nkx2.2 and specification of neuronal identity by graded Sonic hedgehog signalling
TLDR
Evidence is provided that Nkx2.2 has a primary role in ventral neuronal patterning and has an essential role in interpreting graded Shh signals and selecting neuronal identity. Expand
Differential Expression of LIM Homeobox Genes among Motor Neuron Subpopulations in the Developing Chick Brain Stem
TLDR
In 2- to 7-day chick embryos, it is found that genes of the LIM homeobox family are expressed differentially among cranial motor nuclei, consistent with a role of these transcription factors in determining neuronal phenotype and axonal pathfinding. Expand
Topographic organization of embryonic motor neurons defined by expression of LIM homeobox genes
TLDR
The results suggest that LIM homeobox genes contribute to the generation of motor neuron diversity and may confer subclasses of motor neurons with the ability to select specific axon pathways, thereby initiating the topographic organization of motor projections. Expand
Motoneuron fate specification revealed by patterned LIM homeobox gene expression in embryonic zebrafish.
TLDR
The patterned distribution of different primary motoneuronal types within the zebrafish spinal cord follows the patterned expression of LIM homeobox genes, and this reflects a highly resolved system of positional information controlling gene transcription. Expand
A LIM-homeodomain combinatorial code for motor-neuron pathway selection
TLDR
It is shown that Drosophila lim3 is expressed by a specific subset of islet-expressing motor neurons and that mutating or misexpressing lim3 switches motor-neuron projections predictably, providing evidence that lim3 and islet constitute a combinatorial code that generates distinct motor-NEuron identities. Expand
Neuronal patterning by BMPs: a requirement for GDF7 in the generation of a discrete class of commissural interneurons in the mouse spinal cord.
TLDR
It is found that GDF7 can promote the differentiation in vitro of two dorsal sensory interneuron classes, D1A and D1B neurons, which suggest that BMP signaling may have a prominent role in the assignment of neuronal identity within the mammalian CNS. Expand
...
1
2
3
4
5
...