PMID- 22031887 OWN - NLM STAT- MEDLINE DCOM- 20111219 LR - 20211020 IS - 1529-2401 (Electronic) IS - 0270-6474 (Print) IS - 0270-6474 (Linking) VI - 31 IP - 43 DP - 2011 Oct 26 TI - A Shh/miR-206/BDNF cascade coordinates innervation and formation of airway smooth muscle. PG - 15407-15 LID - 10.1523/JNEUROSCI.2745-11.2011 [doi] AB - Dysfunctional neural control of airway smooth muscle (ASM) is involved in inflammatory diseases, such as asthma. However, neurogenesis in the lung is poorly understood. This study uses mouse models to investigate developmental mechanisms of ASM innervation, a process that is highly coordinated with ASM formation during lung branching morphogenesis. We show that brain-derived neurotrophic factor (BDNF) is an essential ASM-derived signal for innervation. Although BDNF mRNA expression is temporally dissociated with ASM formation and innervation, BDNF protein is coordinately produced through post-transcriptional suppression by miR-206. Using a combination of chemical and genetic approaches to modulate sonic hedgehog (Shh) signaling, a pathway essential for lung branching and ASM formation, we show that Shh signaling blocks miR-206 expression, which in turn increases BDNF protein expression. Together, our work uncovers a functional cascade that involves Shh, miR-206 and BDNF to coordinate ASM formation and innervation. FAU - Radzikinas, Kelsi AU - Radzikinas K AD - The Pulmonary Center, Department of Medicine, Boston University School of Medicine, Boston, Massachusetts 02118, USA. FAU - Aven, Linh AU - Aven L FAU - Jiang, Zhihua AU - Jiang Z FAU - Tran, Thanh AU - Tran T FAU - Paez-Cortez, Jesus AU - Paez-Cortez J FAU - Boppidi, Karthik AU - Boppidi K FAU - Lu, Jining AU - Lu J FAU - Fine, Alan AU - Fine A FAU - Ai, Xingbin AU - Ai X LA - eng GR - R01 AG034939/AG/NIA NIH HHS/United States GR - R01 AG034939-01/AG/NIA NIH HHS/United States GR - R01 AG034939-02/AG/NIA NIH HHS/United States GR - R01 AG034939-03/AG/NIA NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't PL - United States TA - J Neurosci JT - The Journal of neuroscience : the official journal of the Society for Neuroscience JID - 8102140 RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Hedgehog Proteins) RN - 0 (MicroRNAs) RN - 0 (Mirn206 microRNA, mouse) RN - 0 (RNA, Messenger) RN - 0 (Shh protein, mouse) RN - 0 (Tubulin) RN - 0 (beta3 tubulin, mouse) RN - 147336-22-9 (Green Fluorescent Proteins) SB - IM MH - Age Factors MH - Animals MH - Brain-Derived Neurotrophic Factor/genetics/*metabolism MH - Embryo, Mammalian MH - Gene Expression Regulation, Developmental/genetics MH - Green Fluorescent Proteins/genetics MH - Hedgehog Proteins/genetics/*metabolism MH - Mice MH - Mice, Transgenic MH - MicroRNAs/genetics/*metabolism MH - Muscle, Smooth/innervation/*physiology MH - RNA, Messenger/metabolism MH - Respiratory System/*anatomy & histology/embryology/*innervation MH - Signal Transduction/genetics MH - Tubulin/metabolism PMC - PMC3222097 MID - NIHMS336351 EDAT- 2011/10/28 06:00 MHDA- 2011/12/20 06:00 PMCR- 2012/04/26 CRDT- 2011/10/28 06:00 PHST- 2011/10/28 06:00 [entrez] PHST- 2011/10/28 06:00 [pubmed] PHST- 2011/12/20 06:00 [medline] PHST- 2012/04/26 00:00 [pmc-release] AID - 31/43/15407 [pii] AID - 3731687 [pii] AID - 10.1523/JNEUROSCI.2745-11.2011 [doi] PST - ppublish SO - J Neurosci. 2011 Oct 26;31(43):15407-15. doi: 10.1523/JNEUROSCI.2745-11.2011.