title: Control of axon guidance and neurotransmitter phenotype of dB1 hindbrain interneurons by Lim-HD code.
abstract: Hindbrain dorsal interneurons (HDIs) are implicated in receiving, processing, integrating, and transmitting sensory inputs from the periphery and spinal cord, including the vestibular, auditory, and proprioceptive systems. During development, multiple molecularly defined HDI types are set in columns along the dorsoventral axis, before migrating along well-defined trajectories to generate various brainstem nuclei. Major brainstem functions rely on the precise assembly of different interneuron groups and higher brain domains into common circuitries. Yet, knowledge regarding interneuron axonal patterns, synaptic targets, and the transcriptional control that govern their connectivity is sparse. The dB1 class of HDIs is formed in a district dorsomedial position along the hindbrain and gives rise to the inferior olive nuclei, dorsal cochlear nuclei, and vestibular nuclei. dB1 interneurons express various transcription factors (TFs): the pancreatic transcription factor 1a (Ptf1a), the homeobox TF-Lbx1 and the Lim-homeodomain (Lim-HD), and TF Lhx1 and Lhx5. To decipher the axonal and synaptic connectivity of dB1 cells, we have used advanced enhancer tools combined with conditional expression systems and the PiggyBac-mediated DNA transposition system in avian embryos. Multiple ipsilateral and contralateral axonal projections were identified ascending toward higher brain centers, where they formed synapses in the Purkinje cerebellar layer as well as at discrete midbrain auditory and vestibular centers. Decoding the mechanisms that instruct dB1 circuit formation revealed a fundamental role for Lim-HD proteins in regulating their axonal patterns, synaptic targets, and neurotransmitter choice. Together, this study provides new insights into the assembly and heterogeneity of HDIs connectivity and its establishment through the central action of Lim-HD governed programs.
authors: Koret School of Veterinary Medicine, Robert H. Smith Faculty of Agriculture, Food and Environment, Hebrew University of Jerusalem, Rehovot 76100, Israel.
authors: Ayelet
authors: A
authors: Kohl
authors: Developmental Neurobiology Laboratory, European Neuroscience Institute, Göttingen 37077, Germany, and.
authors: Till
authors: T
authors: Marquardt
authors: Department of Medical Neurobiology IMRIC, Hebrew University Medical School, Jerusalem, 91120, Israel avihu.klar@mail.huji.ac.il dalit.seladon@mail.huji.ac.il.
authors: Avihu
authors: A
authors: Klar
authors: Koret School of Veterinary Medicine, Robert H. Smith Faculty of Agriculture, Food and Environment, Hebrew University of Jerusalem, Rehovot 76100, Israel, avihu.klar@mail.huji.ac.il dalit.seladon@mail.huji.ac.il.
authors: Dalit
authors: D
authors: Sela-Donenfeld
mesh_terms: D000818:Animals; D001369:Axons / Q000502:physiology*; D002452:Cell Count; D002642:Chick Embryo; D007395:Interneurons / Q000502:physiology; D060850:LIM-Homeodomain Proteins / Q000502:physiology*; D009419:Nerve Tissue Proteins / Q000502:physiology; D009434:Neural Pathways / Q000166:cytology; D009474:Neurons / Q000502:physiology; D018377:Neurotransmitter Agents / Q000502:physiology*; D012249:Rhombencephalon / Q000166:cytology* / Q000254:growth & development*; D013569:Synapses / Q000502:physiology; D014157:Transcription Factors / Q000502:physiology
chemical_list: D060850:LIM-Homeodomain Proteins; C499523:Lhx1 protein, mouse; C102995:Lhx5 protein, mouse; D009419:Nerve Tissue Proteins; D018377:Neurotransmitter Agents; D014157:Transcription Factors
keywords: Lim-HD proteins; axons; hindbrain; interneurons; neurotransmitter; synapses