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Title: Transcriptional control of axonal guidance and sorting in dorsal interneurons by the Lim-HD proteins Lhx9 and Lhx1

Journal Article · · Neural Development
 [1];  [2];  [2];  [2];  [2];  [3];  [2]
  1. Hebrew University of Jerusalem (Israel); DOE/OSTI
  2. Hebrew University of Jerusalem (Israel)
  3. Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States)
+ Show Author Affiliations

Lim-HD proteins control crucial aspects of neuronal differentiation, including subtype identity and axonal guidance. The Lim-HD proteins Lhx2/9 and Lhx1/5 are expressed in the dorsal spinal interneuron populations dI1 and dI2, respectively. While they are not required for cell fate acquisition, their role in patterning the axonal trajectory of dI1 and dI2 neurons remains incompletely understood. Using newly identified dI1- and dI2-specific enhancers to trace axonal trajectories originating from these interneurons, we found that each population is subdivided into several distinct groups according to their axonal pathways. dI1 neurons project axons rostrally, either ipsior contra-laterally, while dI2 are mostly commissural neurons that project their axons rostrally and caudally. The longitudinal axonal tracks of each neuronal population self-fasciculate to form dI1- and dI2-specific bundles. The dI1 bundles are spatially located ventral relative to dI2 bundles. To examine the functional contribution of Lim-HD proteins to establishment of dI axonal projections, the Lim-HD code of dI neurons was altered by cell-specific ectopic expression. Expression of Lhx1 in dI1 neurons caused a repression of Lhx2/9 and imposed caudal projection to the caudal commissural dI1 neurons. Complementarily, when expressed in dI2 neurons, Lhx9 repressed Lhx1/ 5 and triggered a bias toward rostral projection in otherwise caudally projecting dI2 neurons, and ventral shift of the longitudinal axonal fascicule. The Lim-HD proteins Lhx9 and Lhx1 serve as a binary switch in controlling the rostral versus caudal longitudinal turning of the caudal commissural axons. Lhx1 determines caudal turning and Lhx9 triggers rostral turning.

Research Organization:
Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States)
Sponsoring Organization:
German Research Foundation (DFG); Israel Science Foundation; National Human Genome Research Institute; National Institute for Neurological Disorders and Stroke; USDOE Office of Science (SC), Biological and Environmental Research (BER). Biological Systems Science Division
Grant/Contract Number:
AC02-05CH11231
OSTI ID:
1626638
Journal Information:
Neural Development, Journal Name: Neural Development Journal Issue: 1 Vol. 4; ISSN 1749-8104
Publisher:
BioMed CentralCopyright Statement
Country of Publication:
United States
Language:
English

References (82)

Paired-related murine homeobox gene expressed in the developing sclerotome, kidney, and nervous system journal September 1997
Postnatal phenotype and localization of spinal cord V1 derived interneurons journal January 2005
The use of in ovo electroporation for the rapid analysis of neural-specific murine enhancers journal January 2001
A new class of yeast transcriptional activators journal October 1987
Paths, elongation, and projections of ascending chick embryonic spinal commissural neurons after crossing the floor plate journal August 2008
A Hox Regulatory Network Establishes Motor Neuron Pool Identity and Target-Muscle Connectivity journal November 2005
A Molecular Program for Contralateral Trajectory: Rig-1 Control by LIM Homeodomain Transcription Factors journal August 2008
Separable enhancer sequences regulate the expression of the neural bHLH transcription factor neurogenin 1 journal July 2004
Coordinate Roles for LIM Homeobox Genes in Directing the Dorsoventral Trajectory of Motor Axons in the Vertebrate Limb journal July 2000
Requirement for LIM Homeobox Gene Isl1 in Motor Neuron Generation Reveals a Motor Neuron– Dependent Step in Interneuron Differentiation journal January 1996
LIM Homeodomain Factors Lhx3 and Lhx4 Assign Subtype Identities for Motor Neurons journal December 1998
LIM Factor Lhx3 Contributes to the Specification of Motor Neuron and Interneuron Identity through Cell-Type-Specific Protein-Protein Interactions journal July 2002
Functions of LIM-homeobox genes journal February 2000
The Drosophila islet Gene Governs Axon Pathfinding and Neurotransmitter Identity journal March 1997
Proprioceptor Pathway Development Is Dependent on MATH1 journal May 2001
Crossinhibitory Activities of Ngn1 and Math1 Allow Specification of Distinct Dorsal Interneurons journal August 2001
Topographic Motor Projections in the Limb Imposed by LIM Homeodomain Protein Regulation of Ephrin-A:EphA Interactions journal May 2003
Synchronization of Neurogenesis and Motor Neuron Specification by Direct Coupling of bHLH and Homeodomain Transcription Factors journal June 2003
A Postmitotic Role for Isl-Class LIM Homeodomain Proteins in the Assignment of Visceral Spinal Motor Neuron Identity journal February 2004
Novel sites of expression of the bHLH gene NSCL1 in the developing nervous system journal December 2002
Specification of dorsal spinal cord interneurons journal February 2003
A LIM-homeodomain combinatorial code for motor-neuron pathway selection journal January 1999
Motor neuron columnar fate imposed by sequential phases of Hox-c activity journal October 2003
In vivo enhancer analysis of human conserved non-coding sequences journal November 2006
Ultraconservation identifies a small subset of extremely constrained developmental enhancers journal January 2008
VISTA Enhancer Browser--a database of tissue-specific human enhancers journal January 2007
Neuronal patterning by BMPs: a requirement for GDF7 in the generation of a discrete class of commissural interneurons in the mouse spinal cord journal November 1998
Anterior-Posterior Guidance of Commissural Axons by Wnt-Frizzled Signaling journal December 2003
The Molecular Biology of Axon Guidance journal November 1996
The Specification of Dorsal cell Fates in the Vertebrate Central Nervous System journal March 1999
Transcriptional Codes and the Control of Neuronal Identity journal March 2002
Sequential roles for Mash1 and Ngn2 in the generation of dorsal spinal cord interneurons journal June 2005
Lhx1 and Lhx5 maintain the inhibitory-neurotransmitter status of interneurons in the dorsal spinal cord journal January 2007
Guidance of commissural growth cones at the floor plate in embryonic rat spinal cord journal June 1990
Progenitors of dorsal commissural interneurons are defined by MATH1 expression journal March 1998
Engrailed-1 and netrin-1 regulate axon pathfinding by association interneurons that project to motor neurons journal October 1999
Commissural axon pathfinding on the contralateral side of the floor plate: a role for B-class ephrins in specifying the dorsoventral position of longitudinally projecting commissural axons journal December 2001
Manipulating Robo Expression In Vivo Perturbs Commissural Axon Pathfinding in the Chick Spinal Cord journal August 2008
Mammalian BarH1Confers Commissural Neuron Identity on Dorsal Cells in the Spinal Cord journal March 2003
Paired-related murine homeobox gene expressed in the developing sclerotome, kidney, and nervous system journal September 1997
Diversity of contralateral commissural projections in the embryonic rodent spinal cord journal January 2004
Postnatal phenotype and localization of spinal cord V1 derived interneurons journal January 2005
The use of in ovo electroporation for the rapid analysis of neural-specific murine enhancers journal January 2001
A new class of yeast transcriptional activators journal October 1987
Coordinate Roles for LIM Homeobox Genes in Directing the Dorsoventral Trajectory of Motor Axons in the Vertebrate Limb journal July 2000
Requirement for LIM Homeobox Gene Isl1 in Motor Neuron Generation Reveals a Motor Neuron– Dependent Step in Interneuron Differentiation journal January 1996
LIM Homeodomain Factors Lhx3 and Lhx4 Assign Subtype Identities for Motor Neurons journal December 1998
LIM Factor Lhx3 Contributes to the Specification of Motor Neuron and Interneuron Identity through Cell-Type-Specific Protein-Protein Interactions journal July 2002
Functions of LIM-homeobox genes journal February 2000
The Drosophila islet Gene Governs Axon Pathfinding and Neurotransmitter Identity journal March 1997
Proprioceptor Pathway Development Is Dependent on MATH1 journal May 2001
Crossinhibitory Activities of Ngn1 and Math1 Allow Specification of Distinct Dorsal Interneurons journal August 2001
Topographic Motor Projections in the Limb Imposed by LIM Homeodomain Protein Regulation of Ephrin-A:EphA Interactions journal May 2003
Synchronization of Neurogenesis and Motor Neuron Specification by Direct Coupling of bHLH and Homeodomain Transcription Factors journal June 2003
A Postmitotic Role for Isl-Class LIM Homeodomain Proteins in the Assignment of Visceral Spinal Motor Neuron Identity journal February 2004
RETRACTED: Novel sites of expression of the bHLH gene NSCL1 in the developing nervous system journal November 2002
Specification of dorsal spinal cord interneurons journal February 2003
Paths, elongation, and projections of ascending chick embryonic spinal commissural neurons after crossing the floor plate journal August 2008
A Hox Regulatory Network Establishes Motor Neuron Pool Identity and Target-Muscle Connectivity journal November 2005
A Molecular Program for Contralateral Trajectory: Rig-1 Control by LIM Homeodomain Transcription Factors journal August 2008
Separable enhancer sequences regulate the expression of the neural bHLH transcription factor neurogenin 1 journal July 2004
A LIM-homeodomain combinatorial code for motor-neuron pathway selection journal January 1999
Motor neuron columnar fate imposed by sequential phases of Hox-c activity journal October 2003
In vivo enhancer analysis of human conserved non-coding sequences journal November 2006
Ultraconservation identifies a small subset of extremely constrained developmental enhancers journal January 2008
Sonic hedgehog guides commissural axons along the longitudinal axis of the spinal cord journal January 2005
Dynamic regulation of axon guidance journal October 2001
Proteolysis and membrane capture of F-spondin generates combinatorial guidance cues from a single molecule journal September 2007
VISTA Enhancer Browser--a database of tissue-specific human enhancers journal January 2007
Neuronal patterning by BMPs: a requirement for GDF7 in the generation of a discrete class of commissural interneurons in the mouse spinal cord journal November 1998
Anterior-Posterior Guidance of Commissural Axons by Wnt-Frizzled Signaling journal December 2003
The Molecular Biology of Axon Guidance journal November 1996
The Specification of Dorsal cell Fates in the Vertebrate Central Nervous System journal March 1999
Transcriptional Codes and the Control of Neuronal Identity journal March 2002
Sequential roles for Mash1 and Ngn2 in the generation of dorsal spinal cord interneurons journal June 2005
Lhx1 and Lhx5 maintain the inhibitory-neurotransmitter status of interneurons in the dorsal spinal cord journal January 2007
Guidance of commissural growth cones at the floor plate in embryonic rat spinal cord journal June 1990
Progenitors of dorsal commissural interneurons are defined by MATH1 expression journal March 1998
Engrailed-1 and netrin-1 regulate axon pathfinding by association interneurons that project to motor neurons journal October 1999
Commissural axon pathfinding on the contralateral side of the floor plate: a role for B-class ephrins in specifying the dorsoventral position of longitudinally projecting commissural axons journal December 2001
Manipulating Robo Expression In Vivo Perturbs Commissural Axon Pathfinding in the Chick Spinal Cord journal August 2008
Mammalian BarH1Confers Commissural Neuron Identity on Dorsal Cells in the Spinal Cord journal March 2003

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Cell type specific, traceable gene silencing for functional gene analysis during vertebrate neural development journal August 2011
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Expression of the Lhx genes apterous and lim1 in an errant polychaete: implications for bilaterian appendage evolution, neural development, and muscle diversification journal January 2013
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Uncovering Genomic Causes of Co-Morbidity in Epilepsy: Gene-Driven Phenotypic Characterization of Rare Microdeletions journal August 2011
Distinct Cis Regulatory Elements Govern the Expression of TAG1 in Embryonic Sensory Ganglia and Spinal Cord journal February 2013
Bilaterally Symmetric Populations of Chicken dI1 (Commissural) Axons Cross the Floor Plate Independently of Each Other journal April 2013
Three-Dimensional Distribution of Sensory Stimulation-Evoked Neuronal Activity of Spinal Dorsal Horn Neurons Analyzed by In Vivo Calcium Imaging journal August 2014
The Lhx9-integrin pathway is essential for positioning of the proepicardial organ text January 2016
Guidance of longitudinally projecting axons in the developing central nervous system journal January 2012
Molecular and cellular development of spinal cord locomotor circuitry journal June 2015
Rostral growth of commissural axons requires the cell adhesion molecule MDGA2 text January 2011
Post-crossing segment of dI1 commissural axons forms collateral branches to motor neurons in the developing spinal cord journal July 2018
Diverse spinal commissural neuron populations revealed by fate mapping and molecular profiling using a novel Robo3 Cre mouse journal June 2019
Transcriptional regulation of guidance at the midline and in motor circuits journal August 2013
Roles of axon guidance molecules in neuronal wiring in the developing spinal cord journal April 2019
Neural crest and Schwann cell progenitor-derived melanocytes are two spatially segregated populations similarly regulated by Foxd3 journal July 2013
The Transcription Factor LHX1 Regulates the Survival and Directed Migration of POA-derived Cortical Interneurons journal April 2018
Spinal dI2 interneurons regulate the stability of bipedal stepping posted_content January 2020
Developmental origin of long-range neurons in the superficial dorsal spinal cord journal November 2017
Importance of patient selection criteria in determining diagnostic copy number variations in patients with multiple congenital anomaly/mental retardation journal May 2019
Making sense out of spinal cord somatosensory development journal October 2016

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59 BASIC BIOLOGICAL SCIENCES
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