title: Lineage and stage specific requirement for Dicer1 in sympathetic ganglia and adrenal medulla formation and maintenance.
abstract: The development of sympathetic neurons and chromaffin cells is differentially controlled at distinct stages by various extrinsic and intrinsic signals. Here we use conditional deletion of Dicer1 in neural crest cells and noradrenergic neuroblasts to identify stage specific functions in sympathoadrenal lineages. Conditional Dicer1 knockout in neural crest cells of Dicer1(Wnt1Cre) mice results in a rapid reduction in the size of developing sympathetic ganglia and adrenal medulla. In contrast, Dicer1 elimination in noradrenergic neuroblasts of Dicer1(DbhiCre) animals affects sympathetic neuron survival starting at late embryonic stages and chromaffin cells persist at least until postnatal week 1. A differential function of Dicer1 signaling for the development of embryonic noradrenergic and cholinergic sympathetic neurons is demonstrated by the selective increase in the expression of Tlx3 and the cholinergic marker genes VAChT and ChAT at E16.5. The number of Dbh, Th and TrkA expressing noradrenergic neurons is strongly decreased in Dicer1-deficient sympathetic ganglia at birth, whereas Tlx3(+)/ Ret(+) cholinergic neurons cells are spared from cell death. The postnatal death of chromaffin cells is preceded by the loss of Ascl1, mir-375 and Pnmt and an increase in the markers Ret and NF-M, which suggests that Dicer1 is required for the maintenance of chromaffin cell differentiation and survival. Taken together, these findings demonstrate distinct stage and lineage specific functions of Dicer1 signaling in differentiation and survival of sympathetic neurons and adrenal chromaffin cells.
authors: Max-Planck-Institute for Brain Research, Research Group Developmental Neurobiology, Max-von-Laue-Street 4, 60438 Frankfurt/Main, Germany.
authors: Jutta
authors: J
authors: Stubbusch
authors: Albert-Ludwigs-University Freiburg, Institute of Anatomy& Cell Biology, Albert-Street 17, 79104 Freiburg, Germany.
authors: Priyanka
authors: P
authors: Narasimhan
authors: Max-Planck-Institute for Brain Research, Research Group Developmental Neurobiology, Max-von-Laue-Street 4, 60438 Frankfurt/Main, Germany.
authors: Melanie
authors: M
authors: Hennchen
authors: Albert-Ludwigs-University Freiburg, Institute of Anatomy& Cell Biology, Albert-Street 17, 79104 Freiburg, Germany.
authors: Katrin
authors: K
authors: Huber
authors: Albert-Ludwigs-University Freiburg, Institute of Anatomy& Cell Biology, Albert-Street 17, 79104 Freiburg, Germany.
authors: Klaus
authors: K
authors: Unsicker
authors: Max-Planck-Institute for Brain Research, Research Group Developmental Neurobiology, Max-von-Laue-Street 4, 60438 Frankfurt/Main, Germany; Institute of Clinical Neuroanatomy, Goethe-University Frankfurt, Theodor-Stern-Kai 7, Frankfurt/Main, Germany.
authors: Uwe
authors: U
authors: Ernsberger
authors: Max-Planck-Institute for Brain Research, Research Group Developmental Neurobiology, Max-von-Laue-Street 4, 60438 Frankfurt/Main, Germany; Institute of Clinical Neuroanatomy, Goethe-University Frankfurt, Theodor-Stern-Kai 7, Frankfurt/Main, Germany. Electronic address: hermann.rohrer@brain.mpg.de.
authors: Hermann
authors: H
authors: Rohrer
mesh_terms: D000313:Adrenal Medulla / Q000166:cytology* / Q000196:embryology / Q000294:innervation / Q000378:metabolism; D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism; D002470:Cell Survival; D019439:Chromaffin Cells / Q000166:cytology* / Q000378:metabolism; D053487:DEAD-box RNA Helicases / Q000378:metabolism*; D005728:Ganglia, Sympathetic / Q000166:cytology* / Q000196:embryology / Q000378:metabolism; D051379:Mice; D009432:Neural Crest / Q000378:metabolism; D043244:Ribonuclease III / Q000378:metabolism*; D013234:Stem Cells / Q000378:metabolism
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D053487:DEAD-box RNA Helicases; D043244:Ribonuclease III; C499317:Ascl1 protein, mouse; C509781:Dicer1 protein, mouse
keywords: Cholinergic; Chromaffin cell; Dicer1; Noradrenergic; Survival; Sympathetic neuron