Mnx1

Summary

Gene Symbol: Mnx1
Description: motor neuron and pancreas homeobox 1
Alias: HB9, Hlxb9, MNR2, motor neuron and pancreas homeobox protein 1, homeobox gene HB9, homeobox protein HB9
Species: mouse
Products:     Mnx1

Top Publications

  1. Jacquemin P, Lemaigre F, Rousseau G. The Onecut transcription factor HNF-6 (OC-1) is required for timely specification of the pancreas and acts upstream of Pdx-1 in the specification cascade. Dev Biol. 2003;258:105-16 pubmed
    ..Together with the known role of HNF-6 in pancreatic endocrine cell differentiation, our data point to HNF-6 as a key regulator of pancreas development. ..
  2. Haumaitre C, Barbacci E, Jenny M, Ott M, Gradwohl G, Cereghini S. Lack of TCF2/vHNF1 in mice leads to pancreas agenesis. Proc Natl Acad Sci U S A. 2005;102:1490-5 pubmed
    ..At earlier stages, only a dorsal bud rudiment forms transiently and expresses the transcription factors Ipf1 and Hlxb9 but lacks the key transcription factor involved in the acquisition of a pancreatic fate, Ptf1a, as well as all ..
  3. Arber S, Ladle D, Lin J, Frank E, Jessell T. ETS gene Er81 controls the formation of functional connections between group Ia sensory afferents and motor neurons. Cell. 2000;101:485-98 pubmed
    ..ER81 therefore controls a late step in the establishment of functional sensory-motor circuitry in the developing spinal cord. ..
  4. Lin W, Burgess R, Dominguez B, Pfaff S, Sanes J, Lee K. Distinct roles of nerve and muscle in postsynaptic differentiation of the neuromuscular synapse. Nature. 2001;410:1057-64 pubmed
    ..In contrast, the subsequent stages of synaptic growth and maintenance require nerve-derived agrin, and a second nerve-derived signal that disperses ectopic postsynaptic apparatus. ..
  5. Bai C, Stephen D, Joyner A. All mouse ventral spinal cord patterning by hedgehog is Gli dependent and involves an activator function of Gli3. Dev Cell. 2004;6:103-15 pubmed
    ..Therefore, in the spinal cord all Hh signaling is Gli dependent. Furthermore, a combination of Gli2 and Gli3 is required to regulate motor neuron development and spatial patterning of ventral spinal cord progenitors. ..
  6. Agalliu D, Takada S, Agalliu I, McMahon A, Jessell T. Motor neurons with axial muscle projections specified by Wnt4/5 signaling. Neuron. 2009;61:708-20 pubmed publisher
    ..Thus, two dorsoventral signaling pathways, mediated by Shh and Wnt4/5, are required to establish an early binary divergence in motor neuron columnar identity. ..
  7. Lee S, Lee B, Ruiz E, Pfaff S. Olig2 and Ngn2 function in opposition to modulate gene expression in motor neuron progenitor cells. Genes Dev. 2005;19:282-94 pubmed
  8. Kim N, Burden S. MuSK controls where motor axons grow and form synapses. Nat Neurosci. 2008;11:19-27 pubmed
  9. Zheng K, Li H, Zhu Y, Zhu Q, Qiu M. MicroRNAs are essential for the developmental switch from neurogenesis to gliogenesis in the developing spinal cord. J Neurosci. 2010;30:8245-50 pubmed publisher
    ..By contrast, the early patterning and development of motor neurons were not affected in the mutant spinal cord tissue. ..

More Information

Publications67

  1. Wijgerde M, McMahon J, Rule M, McMahon A. A direct requirement for Hedgehog signaling for normal specification of all ventral progenitor domains in the presumptive mammalian spinal cord. Genes Dev. 2002;16:2849-64 pubmed
    ..Thus, Hh signaling is essential for organizing ventral cell pattern, possibly through the control of differential cell affinities. ..
  2. Berbari N, Kin N, Sharma N, Michaud E, Kesterson R, Yoder B. Mutations in Traf3ip1 reveal defects in ciliogenesis, embryonic development, and altered cell size regulation. Dev Biol. 2011;360:66-76 pubmed publisher
  3. Eggenschwiler J, Espinoza E, Anderson K. Rab23 is an essential negative regulator of the mouse Sonic hedgehog signalling pathway. Nature. 2001;412:194-8 pubmed
    ..The data indicate that dorsalizing signals activate transcription of Rab23 in order to silence the Shh pathway in dorsal neural cells. ..
  4. Stolt C, Schlierf A, Lommes P, Hillgärtner S, Werner T, Kosian T, et al. SoxD proteins influence multiple stages of oligodendrocyte development and modulate SoxE protein function. Dev Cell. 2006;11:697-709 pubmed
    ..Our studies reveal a complex regulatory network between different groups of Sox proteins that is essential for proper progression of oligodendrocyte development. ..
  5. Eggenschwiler J, Bulgakov O, Qin J, Li T, Anderson K. Mouse Rab23 regulates hedgehog signaling from smoothened to Gli proteins. Dev Biol. 2006;290:1-12 pubmed
    ..Instead, Rab23 appears to regulate subcellular localization of essential components of the Hedgehog pathway that act downstream of Smoothened and upstream of Gli proteins. ..
  6. Patel T, Kramer I, Kucera J, Niederkofler V, Jessell T, Arber S, et al. Peripheral NT3 signaling is required for ETS protein expression and central patterning of proprioceptive sensory afferents. Neuron. 2003;38:403-16 pubmed
    ..Finally, addition of NT3 to DRG explant cultures resulted in induction of ER81 protein. Our data indicate that NT3 mediates the formation of proprioceptive afferent-motor neuron connections via regulation of ER81. ..
  7. Vermeren M, Maro G, Bron R, McGonnell I, Charnay P, Topilko P, et al. Integrity of developing spinal motor columns is regulated by neural crest derivatives at motor exit points. Neuron. 2003;37:403-15 pubmed
    ..Thus, before the formation of a mature transitional zone at the MEP, BC cells maintain a cell-tight boundary that allows motor axons to cross but blocks neuron migration. ..
  8. Arber S, Han B, Mendelsohn M, Smith M, Jessell T, Sockanathan S. Requirement for the homeobox gene Hb9 in the consolidation of motor neuron identity. Neuron. 1999;23:659-74 pubmed
    The homeobox gene Hb9, like its close relative MNR2, is expressed selectively by motor neurons (MNs) in the developing vertebrate CNS...
  9. Luria V, Krawchuk D, Jessell T, Laufer E, Kania A. Specification of motor axon trajectory by ephrin-B:EphB signaling: symmetrical control of axonal patterning in the developing limb. Neuron. 2008;60:1039-53 pubmed publisher
    ..The involvement of ephrin:Eph signaling in guiding both sets of motor axons raises the possibility that other signaling systems function primarily to refine or modulate a core Eph signaling program. ..
  10. Weatherbee S, Niswander L, Anderson K. A mouse model for Meckel syndrome reveals Mks1 is required for ciliogenesis and Hedgehog signaling. Hum Mol Genet. 2009;18:4565-75 pubmed publisher
    ..Thus the disruption of Hh signaling can explain many, but not all, of the defects caused by loss of Mks1...
  11. Wu Y, Wang G, Scott S, Capecchi M. Hoxc10 and Hoxd10 regulate mouse columnar, divisional and motor pool identity of lumbar motoneurons. Development. 2008;135:171-82 pubmed
    ..Together, these results show that Hoxc10 and Hoxd10 play key roles in establishing lumbar motoneuron columnar, divisional and motor pool identity. ..
  12. Kramer E, Knott L, Su F, Dessaud E, Krull C, Helmbacher F, et al. Cooperation between GDNF/Ret and ephrinA/EphA4 signals for motor-axon pathway selection in the limb. Neuron. 2006;50:35-47 pubmed
    ..This phenotype is enhanced in mutant mice lacking Ret and EphA4. Thus, Ret and EphA4 signals cooperate to enforce the precision of the same binary choice in motor-axon guidance. ..
  13. Hippenmeyer S, Vrieseling E, Sigrist M, Portmann T, Laengle C, Ladle D, et al. A developmental switch in the response of DRG neurons to ETS transcription factor signaling. PLoS Biol. 2005;3:e159 pubmed
    ..Together, our findings indicate that DRG sensory neurons exhibit a temporal developmental switch that can be revealed by distinct responses to ETS transcription factor signaling at sequential steps of neuronal maturation. ..
  14. Eggenschwiler J, Anderson K. Dorsal and lateral fates in the mouse neural tube require the cell-autonomous activity of the open brain gene. Dev Biol. 2000;227:648-60 pubmed
    ..The data indicate that opb(+) could act as either a novel component of a dorsalizing pathway or a novel intracellular negative regulator of the Shh signal transduction pathway. ..
  15. Caspary T, Larkins C, Anderson K. The graded response to Sonic Hedgehog depends on cilia architecture. Dev Cell. 2007;12:767-78 pubmed
    ..Thus, normal structure of the ciliary axoneme is required for the cell to translate different levels of Shh ligand into differential regulation of the Gli transcription factors that implement Hedgehog signals. ..
  16. Gosgnach S, Lanuza G, Butt S, Saueressig H, Zhang Y, Velasquez T, et al. V1 spinal neurons regulate the speed of vertebrate locomotor outputs. Nature. 2006;440:215-9 pubmed
  17. Wilson J, Hartley R, Maxwell D, Todd A, Lieberam I, Kaltschmidt J, et al. Conditional rhythmicity of ventral spinal interneurons defined by expression of the Hb9 homeodomain protein. J Neurosci. 2005;25:5710-9 pubmed
    ..in which expression of green fluorescent protein is driven by the promoter for the homeodomain transcription factor Hb9, as well as Hb9-lacZ knock-in mice, we describe a novel population of glutamatergic interneurons located adjacent ..
  18. Vallstedt A, Klos J, Ericson J. Multiple dorsoventral origins of oligodendrocyte generation in the spinal cord and hindbrain. Neuron. 2005;45:55-67 pubmed
    ..Based on these findings, we propose that oligodendrocytes derive from several distinct positional origins and that the activation of Olig1/2 at different positions is controlled by distinct genetic programs. ..
  19. Huangfu D, Anderson K. Cilia and Hedgehog responsiveness in the mouse. Proc Natl Acad Sci U S A. 2005;102:11325-30 pubmed
  20. Gogliotti R, Quinlan K, Barlow C, Heier C, Heckman C, DiDonato C. Motor neuron rescue in spinal muscular atrophy mice demonstrates that sensory-motor defects are a consequence, not a cause, of motor neuron dysfunction. J Neurosci. 2012;32:3818-29 pubmed publisher
    ..Using an Hb9-Cre allele, we increased Smn levels autonomously within MNs and demonstrate that MN rescue significantly improves ..
  21. Li X, Dong X, Luo S, Zhang B, Lee D, Ting A, et al. Retrograde regulation of motoneuron differentiation by muscle beta-catenin. Nat Neurosci. 2008;11:262-8 pubmed publisher
    ..Taken together, these observations indicate a role for muscle beta-catenin in presynaptic differentiation and function, identifying a previously unknown retrograde signaling in the synapse formation and synaptic plasticity. ..
  22. De Marco Garcia N, Jessell T. Early motor neuron pool identity and muscle nerve trajectory defined by postmitotic restrictions in Nkx6.1 activity. Neuron. 2008;57:217-31 pubmed publisher
    ..Our findings provide genetic evidence that neurons within motor pools possess an early transcriptional identity that controls target muscle specificity. ..
  23. Wilson J, Cowan A, Brownstone R. Heterogeneous electrotonic coupling and synchronization of rhythmic bursting activity in mouse Hb9 interneurons. J Neurophysiol. 2007;98:2370-81 pubmed
    ..b>Hb9 interneurons, a small population of discretely localized interneurons in the mouse spinal cord, are conditionally ..
  24. Jevsek M, Jaworski A, Polo Parada L, Kim N, Fan J, Landmesser L, et al. CD24 is expressed by myofiber synaptic nuclei and regulates synaptic transmission. Proc Natl Acad Sci U S A. 2006;103:6374-9 pubmed
    ..Because CD24 is also expressed in some neurons, additional experiments will be required to determine whether pre- or postsynaptic CD24 mediates these effects on presynaptic development and function. ..
  25. Chipman P, Franz C, Nelson A, Schachner M, Rafuse V. Neural cell adhesion molecule is required for stability of reinnervated neuromuscular junctions. Eur J Neurosci. 2010;31:238-49 pubmed publisher
    ..Consideration is given to the role of NCAM in terminal Schwann cells for maintaining synaptic integrity and how NCAM dysfunction may contribute to motoneuron disorders. ..
  26. Briscoe J, Sussel L, Serup P, HARTIGAN O CONNOR D, Jessell T, Rubenstein J, et al. Homeobox gene Nkx2.2 and specification of neuronal identity by graded Sonic hedgehog signalling. Nature. 1999;398:622-7 pubmed
    ..Thus, Nkx2.2 has an essential role in interpreting graded Shh signals and selecting neuronal identity. ..
  27. Ma Y, Song M, Park J, Henry Ho H, Hu L, Kurtev M, et al. Regulation of motor neuron specification by phosphorylation of neurogenin 2. Neuron. 2008;58:65-77 pubmed publisher
  28. Luria V, Laufer E. Lateral motor column axons execute a ternary trajectory choice between limb and body tissues. Neural Dev. 2007;2:13 pubmed
    ..When making this choice, medial and lateral LMC axons exhibit different and asymmetric relative preferences for these three trajectories. These data redefine the LMC as a motor column that innervates both limb and body tissues. ..
  29. Thompson N, Gesina E, Scheinert P, Bucher P, Grapin Botton A. RNA profiling and chromatin immunoprecipitation-sequencing reveal that PTF1a stabilizes pancreas progenitor identity via the control of MNX1/HLXB9 and a network of other transcription factors. Mol Cell Biol. 2012;32:1189-99 pubmed publisher
    ..We demonstrate that Mnx1, a gene that is absolutely required in pancreas progenitors, is a major direct target of PTF1a and is regulated by ..
  30. Bolis A, Coviello S, Bussini S, Dina G, Pardini C, Previtali S, et al. Loss of Mtmr2 phosphatase in Schwann cells but not in motor neurons causes Charcot-Marie-Tooth type 4B1 neuropathy with myelin outfoldings. J Neurosci. 2005;25:8567-77 pubmed
    ..Thus, therapeutical approaches might be designed in the future to specifically deliver the Mtmr2 phospholipid phosphatase to Schwann cells in affected nerves. ..
  31. Chen J, Huang Y, Mazzoni E, Tan G, Zavadil J, Wichterle H. Mir-17-3p controls spinal neural progenitor patterning by regulating Olig2/Irx3 cross-repressive loop. Neuron. 2011;69:721-35 pubmed publisher
  32. Stam F, Hendricks T, Zhang J, Geiman E, Francius C, Labosky P, et al. Renshaw cell interneuron specialization is controlled by a temporally restricted transcription factor program. Development. 2012;139:179-90 pubmed publisher
  33. Ocbina P, Eggenschwiler J, Moskowitz I, Anderson K. Complex interactions between genes controlling trafficking in primary cilia. Nat Genet. 2011;43:547-53 pubmed publisher
  34. Tran P, Haycraft C, Besschetnova T, Turbe Doan A, Stottmann R, Herron B, et al. THM1 negatively modulates mouse sonic hedgehog signal transduction and affects retrograde intraflagellar transport in cilia. Nat Genet. 2008;40:403-410 pubmed publisher
    ..Specifically, the aln mutation uncouples the roles of anterograde and retrograde transport in SHH signaling, suggesting that anterograde IFT is required for GLI activation and that retrograde IFT modulates this event. ..
  35. Francius C, Clotman F. Dynamic expression of the Onecut transcription factors HNF-6, OC-2 and OC-3 during spinal motor neuron development. Neuroscience. 2010;165:116-29 pubmed publisher
    ..Together, our data unveil a complex and dynamic expression profile of the OC proteins in spinal MN, which suggests that these factors may participate in regulatory networks that control different steps of motor neuron development. ..
  36. Lieberam I, Agalliu D, Nagasawa T, Ericson J, Jessell T. A Cxcl12-CXCR4 chemokine signaling pathway defines the initial trajectory of mammalian motor axons. Neuron. 2005;47:667-79 pubmed
    ..In its absence, these neurons adopt a dMN-like trajectory, despite preservation of their vMN transcriptional identity. Thus, the status of Cxcr4 signaling helps to determine the initial axonal trajectory of mammalian motor neurons. ..
  37. Li H, Arber S, Jessell T, Edlund H. Selective agenesis of the dorsal pancreas in mice lacking homeobox gene Hlxb9. Nat Genet. 1999;23:67-70 pubmed
    ..The initial stages of pancreatic development, however, still occur in Pdx1-deficient mice. Hlxb9 (encoding Hb9; ref...
  38. Haase G, Dessaud E, Garces A, de Bovis B, Birling M, Filippi P, et al. GDNF acts through PEA3 to regulate cell body positioning and muscle innervation of specific motor neuron pools. Neuron. 2002;35:893-905 pubmed
    ..Thus, GDNF acts as a peripheral signal to induce PEA3 expression in specific motor neuron pools thereby regulating both cell body position and muscle innervation. ..
  39. Huangfu D, Liu A, Rakeman A, Murcia N, Niswander L, Anderson K. Hedgehog signalling in the mouse requires intraflagellar transport proteins. Nature. 2003;426:83-7 pubmed
    ..Our data show that IFT machinery has an essential and vertebrate-specific role in Hedgehog signal transduction. ..
  40. Scardigli R, Schuurmans C, Gradwohl G, Guillemot F. Crossregulation between Neurogenin2 and pathways specifying neuronal identity in the spinal cord. Neuron. 2001;31:203-17 pubmed
    ..Thus, neuronal differentiation involves crossregulatory interactions between a bHLH-driven program of neurogenesis and genetic pathways specifying progenitor and neuronal identity in the spinal cord. ..
  41. Yang X, Arber S, William C, Li L, Tanabe Y, Jessell T, et al. Patterning of muscle acetylcholine receptor gene expression in the absence of motor innervation. Neuron. 2001;30:399-410 pubmed
    ..Our results demonstrate that AChR expression is patterned in the absence of innervation, raising the possibility that similarly prepatterned muscle-derived cues restrict axon growth and initiate synapse formation. ..
  42. Lin W, Dominguez B, Yang J, Aryal P, Brandon E, Gage F, et al. Neurotransmitter acetylcholine negatively regulates neuromuscular synapse formation by a Cdk5-dependent mechanism. Neuron. 2005;46:569-79 pubmed
    ..Genetic elimination of Cdk5 or blocking ACh production prevents the dispersion of AChR clusters in agrin mutants. Therefore, we propose that ACh negatively regulates neuromuscular synapse formation through a Cdk5-dependent mechanism. ..
  43. Itoh A, Horiuchi M, Wakayama K, Xu J, Bannerman P, Pleasure D, et al. ZPK/DLK, a mitogen-activated protein kinase kinase kinase, is a critical mediator of programmed cell death of motoneurons. J Neurosci. 2011;31:7223-8 pubmed publisher
    ..Nuclear HB9/MNX1-positive motoneuron pools were generated similarly in the spinal cord of both ZPK/DLK-deficient and wild-type ..
  44. Masahira N, Takebayashi H, Ono K, Watanabe K, Ding L, Furusho M, et al. Olig2-positive progenitors in the embryonic spinal cord give rise not only to motoneurons and oligodendrocytes, but also to a subset of astrocytes and ependymal cells. Dev Biol. 2006;293:358-69 pubmed
    ..These findings demonstrate that motoneurons and oligodendrocytes are not the only cell types originating from this domain. ..
  45. Tarchini B, Huynh T, Cox G, Duboule D. HoxD cluster scanning deletions identify multiple defects leading to paralysis in the mouse mutant Ironside. Genes Dev. 2005;19:2862-76 pubmed
    ..These results highlight the importance of a systematic approach when studying such clustered gene families, and give insights into the function and regulation of Hox and Evx2 genes during early spinal cord development. ..
  46. Stolt C, Lommes P, Sock E, Chaboissier M, Schedl A, Wegner M. The Sox9 transcription factor determines glial fate choice in the developing spinal cord. Genes Dev. 2003;17:1677-89 pubmed
  47. Persson M, Stamataki D, te Welscher P, Andersson E, Böse J, Ruther U, et al. Dorsal-ventral patterning of the spinal cord requires Gli3 transcriptional repressor activity. Genes Dev. 2002;16:2865-78 pubmed
    ..Together these data raise the possibility that Gli proteins act as common mediators integrating Shh signals, and other sources of positional information, to control patterning throughout the ventral neural tube. ..
  48. Lu Q, Sun T, Zhu Z, Ma N, Garcia M, Stiles C, et al. Common developmental requirement for Olig function indicates a motor neuron/oligodendrocyte connection. Cell. 2002;109:75-86 pubmed
    ..Neither Olig gene is required for astrocytes. These findings, together with fate mapping analysis of Olig-expressing cells, indicate that oligodendrocytes are derived from Olig-specified progenitors that give rise also to neurons. ..
  49. Ye F, Chen Y, Hoang T, Montgomery R, Zhao X, Bu H, et al. HDAC1 and HDAC2 regulate oligodendrocyte differentiation by disrupting the beta-catenin-TCF interaction. Nat Neurosci. 2009;12:829-38 pubmed publisher
    ..Thus, crosstalk between HDAC1/2 and the canonical Wnt signaling pathway mediated by TCF7L2 serves as a regulatory mechanism for oligodendrocyte differentiation. ..
  50. Vierkotten J, Dildrop R, Peters T, Wang B, Ruther U. Ftm is a novel basal body protein of cilia involved in Shh signalling. Development. 2007;134:2569-77 pubmed
    ..Furthermore, the absence of Ftm in arthropods underlines the divergence between vertebrate and Drosophila Hh pathways...
  51. Song M, Shirasaki R, Cai C, Ruiz E, Evans S, Lee S, et al. T-Box transcription factor Tbx20 regulates a genetic program for cranial motor neuron cell body migration. Development. 2006;133:4945-55 pubmed
    ..Our study suggests that Tbx20 programs a variety of hindbrain motor neurons for migration, independent of directionality, and in facial neurons is a positive regulator of the non-canonical Wnt signaling pathway. ..
  52. Horn M, Baumann R, Pereira J, Sidiropoulos P, Somandin C, Welzl H, et al. Myelin is dependent on the Charcot-Marie-Tooth Type 4H disease culprit protein FRABIN/FGD4 in Schwann cells. Brain. 2012;135:3567-83 pubmed publisher
  53. Peng C, Yajima H, Burns C, Zon L, Sisodia S, Pfaff S, et al. Notch and MAML signaling drives Scl-dependent interneuron diversity in the spinal cord. Neuron. 2007;53:813-27 pubmed
    ..Thus, our study provides insight into the cell-extrinsic signaling that controls combinatorial transcription factor profiles involved in regulating the process of interneuron subtype diversification. ..
  54. Tuson M, He M, Anderson K. Protein kinase A acts at the basal body of the primary cilium to prevent Gli2 activation and ventralization of the mouse neural tube. Development. 2011;138:4921-30 pubmed publisher
  55. Wu H, Lu Y, Shen C, Patel N, Gan L, Xiong W, et al. Distinct roles of muscle and motoneuron LRP4 in neuromuscular junction formation. Neuron. 2012;75:94-107 pubmed publisher
    ..These observations uncovered distinct roles of LRP4 in motoneurons and muscles in NMJ development. ..
  56. Cortellino S, Wang C, Wang B, Bassi M, Caretti E, Champeval D, et al. Defective ciliogenesis, embryonic lethality and severe impairment of the Sonic Hedgehog pathway caused by inactivation of the mouse complex A intraflagellar transport gene Ift122/Wdr10, partially overlapping with the DNA repair gene Med1/Mbd4. Dev Biol. 2009;325:225-37 pubmed publisher
    ..We conclude that complex A and complex B factors play similar but distinct roles in ciliogenesis and Shh/Gli3 signaling. ..
  57. Sharma K, Sheng H, Lettieri K, Li H, Karavanov A, Potter S, et al. LIM homeodomain factors Lhx3 and Lhx4 assign subtype identities for motor neurons. Cell. 1998;95:817-28 pubmed
    ..Thus, Lhx3 and Lhx4 act in a binary fashion during a brief period in development to specify the trajectory of motor axons from the neural tube. ..
  58. Harrison K, Thaler J, Pfaff S, Gu H, Kehrl J. Pancreas dorsal lobe agenesis and abnormal islets of Langerhans in Hlxb9-deficient mice. Nat Genet. 1999;23:71-5 pubmed
    ..The homeobox gene HLXB9 (encoding HB9) is prominently expressed in adult human pancreas, although its role in pancreas development and ..