title: Transcriptional control of axonal guidance and sorting in dorsal interneurons by the Lim-HD proteins Lhx9 and Lhx1.
abstract: BACKGROUND
  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.
  
  
  RESULTS
  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 ipsi- or 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.
  
  
  CONCLUSIONS
  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.
authors: Department of Medical Neurobiology, IMRIC, Hebrew University, Hadassah Medical School, Jerusalem, Israel. oshria@ekmd.huji.ac.il
authors: Oshri
authors: O
authors: Avraham
authors: Yoav
authors: Y
authors: Hadas
authors: Lilach
authors: L
authors: Vald
authors: Sophie
authors: S
authors: Zisman
authors: Adi
authors: A
authors: Schejter
authors: Axel
authors: A
authors: Visel
authors: Avihu
authors: A
authors: Klar
mesh_terms: D000818:Animals; D001369:Axons / Q000502:physiology*; D019521:Body Patterning / Q000235:genetics; D002454:Cell Differentiation; D002642:Chick Embryo; D018274:Electroporation / Q000379:methods; D004742:Enhancer Elements, Genetic / Q000502:physiology; D018507:Gene Expression Regulation, Developmental / Q000235:genetics; D049452:Green Fluorescent Proteins / Q000235:genetics; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D007395:Interneurons / Q000145:classification / Q000166:cytology*; D060850:LIM-Homeodomain Proteins; D009434:Neural Pathways / Q000196:embryology / Q000502:physiology; D013116:Spinal Cord / Q000166:cytology* / Q000196:embryology; D014157:Transcription Factors
chemical_list: D018398:Homeodomain Proteins; C085473:LHX1 protein, human; C492149:LHX9 protein, human; D060850:LIM-Homeodomain Proteins; D014157:Transcription Factors; D049452:Green Fluorescent Proteins