#PAGE_PARAMS# #ADS_HEAD_SCRIPTS# #MICRODATA#

The Midline Protein Regulates Axon Guidance by Blocking the Reiteration of Neuroblast Rows within the Drosophila Ventral Nerve Cord


Guiding axon growth cones towards their targets is a fundamental process that occurs in a developing nervous system. Several major signaling systems are involved in axon-guidance, and disruption of these systems causes axon-guidance defects. However, the specific role of the environment in which axons navigate in regulating axon-guidance has not been examined in detail. In Drosophila, the ventral nerve cord is divided into segments, and half-segments and the precursor neuroblasts are formed in rows and columns in individual half-segments. The row-wise expression of segment-polarity genes within the neuroectoderm provides the initial row-wise identity to neuroblasts. Here, we show that in embryos mutant for the gene midline, which encodes a T-box DNA binding protein, row-2 neuroblasts and their neuroectoderm adopt a row-5 identity. This reiteration of row-5 ultimately creates a non-permissive zone or a barrier, which prevents the extension of interneuronal longitudinal tracts along their normal anterior-posterior path. While we do not know the nature of the barrier, the axon tracts either stall when they reach this region or project across the midline or towards the periphery along this zone. Previously, we had shown that midline ensures ancestry-dependent fate specification in a neuronal lineage. These results provide the molecular basis for the axon guidance defects in midline mutants and the significance of proper specification of the environment to axon-guidance. These results also reveal the importance of segmental polarity in guiding axons from one segment to the next, and a link between establishment of broad segmental identity and axon guidance.


Vyšlo v časopise: The Midline Protein Regulates Axon Guidance by Blocking the Reiteration of Neuroblast Rows within the Drosophila Ventral Nerve Cord. PLoS Genet 9(12): e32767. doi:10.1371/journal.pgen.1004050
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1004050

Souhrn

Guiding axon growth cones towards their targets is a fundamental process that occurs in a developing nervous system. Several major signaling systems are involved in axon-guidance, and disruption of these systems causes axon-guidance defects. However, the specific role of the environment in which axons navigate in regulating axon-guidance has not been examined in detail. In Drosophila, the ventral nerve cord is divided into segments, and half-segments and the precursor neuroblasts are formed in rows and columns in individual half-segments. The row-wise expression of segment-polarity genes within the neuroectoderm provides the initial row-wise identity to neuroblasts. Here, we show that in embryos mutant for the gene midline, which encodes a T-box DNA binding protein, row-2 neuroblasts and their neuroectoderm adopt a row-5 identity. This reiteration of row-5 ultimately creates a non-permissive zone or a barrier, which prevents the extension of interneuronal longitudinal tracts along their normal anterior-posterior path. While we do not know the nature of the barrier, the axon tracts either stall when they reach this region or project across the midline or towards the periphery along this zone. Previously, we had shown that midline ensures ancestry-dependent fate specification in a neuronal lineage. These results provide the molecular basis for the axon guidance defects in midline mutants and the significance of proper specification of the environment to axon-guidance. These results also reveal the importance of segmental polarity in guiding axons from one segment to the next, and a link between establishment of broad segmental identity and axon guidance.


Zdroje

1. KiddT, BlandKS, GoodmanCS (1999) Slit is the midline repellent for the robo receptor in Drosophila. Cell 96: 785–794.

2. RajagopalanS, VivancosV, NicolasE, DicksonBJ (2000) Selecting a longitudinal pathway: Robo receptors specify the lateral position of axons in the Drosophila CNS. Cell 103: 1033–1045.

3. SimpsonJH, BlandKS, FetterRD, GoodmanCS (2000) Short-range and long-range guidance by Slit and its Robo receptors: a combinatorial code of Robo receptors controls lateral position. Cell 103: 1019–1032.

4. HarrisR, SabatelliLM, SeegerMA (1996) Guidance cues at the Drosophila CNS midline: identification and characterization of two Drosophila Netrin/UNC-6 homologs. Neuron 17: 217–228.

5. KolodziejPA, TimpeLC, MitchellKJ, FriedSR, GoodmanCS, et al. (1996) frazzled encodes a Drosophila member of the DCC immunoglobulin subfamily and is required for CNS and motor axon guidance. Cell 87: 197–204.

6. MitchellKJ, DoyleJL, SerafiniT, KennedyTE, Tessier-LavigneM, et al. (1996) Genetic analysis of Netrin genes in Drosophila: Netrins guide CNS commissural axons and peripheral motor axons. Neuron 17: 203–215.

7. BhatKM, GaziovaI, KrishnanS (2007) Regulation of axon guidance by Slit and Netrin signaling in the Drosophila nerve ventral nerve cord. Genetics 176: 2235–2246.

8. BrankatschkM, DicksonBJ (2006) Netrins guide Drosophila commissural axons at short range. Nat Neurosci 9: 188–194.

9. HidalgoA, BrandAH (1997) Targeted neuronal ablation: the role of pioneer neurons in guidance and fasciculation in the CNS of Drosophila. Development 124: 3253–3262.

10. MeriandaTT, BottaV, BhatKM (2005) Patched regulation of axon guidance is by specifying neural identity in the Drosophila nerve cord. Dev Genes Evol 215: 285–296.

11. BhatKM (1996) The patched signaling pathway mediates repression of gooseberry allowing neuroblast specification by wingless during Drosophila neurogenesis. Development 122: 2921–2932.

12. BhatKM, SchedlP (1997) Requirement for engrailed and invected genes reveals novel regulatory interactions between engrailed/invected, patched, gooseberry and wingless during Drosophila neurogenesis. Development 124: 1675–1688.

13. BhatKM, van BeersEH, BhatP (2000) Sloppy paired acts as the downstream target of wingless in the Drosophila CNS and interaction between sloppy paired and gooseberry inhibits sloppy paired during neurogenesis. Development 127: 655–665.

14. BhatKM (1998) frizzled and frizzled 2 Play a Partially Redundant Role in Wingless Signaling and Have Similar Requirements to Wingless in Neurogenesis. Cell 95: 1027–1036.

15. BhatKM (1999) Segment polarity genes in neuroblast formation and identity specification during Drosophila neurogenesis. Bioessays 21: 472–485.

16. IsshikiT, PearsonB, HolbrookS, DoeCQ (2001) Drosophila neuroblasts sequentially express transcription factors which specify the temporal identity of their neuronal progeny. Cell 106: 511–521.

17. LiX, ErclikT, BertetC, ChenZ, VoutevR, et al. (2013) Temporal patterning of Drosophila medulla neuroblasts controls neural fates. Nature 498: 456–462.

18. PatelNH, SchaferB, GoodmanCS, HolmgrenR (1989) The role of segment polarity genes during Drosophila neurogenesis. Genes Dev 3: 890–904.

19. KispertA, HermannBG (1993) The Brachyury gene encodes a novel DNA binding protein. EMBO J 12: 4898–4899.

20. GaziovaI, BhatKM (2009) Ancestry-independent fate specification and plasticity in the developmental timing of a typical Drosophila neuronal lineage. Development 136: 263–274.

21. PorschM, SauerM, SchulzeS, BahloA, RothM, et al. (2005) The relative role of the T-domain and flanking sequences for developmental control and transcriptional regulation in protein chimeras of Drosophila OMB and ORG-1. Mech Dev 122: 81–96.

22. BassonCT, HuangT, LinRC, BachinskyDR, WeremowiczS, et al. (1999) Different TBX5 interactions in heart and limb defined by Holt-Oram syndrome mutations. Proc Natl Acad Sci U S A 96: 2919–2924.

23. BamshadM, LinRC, LawDJ, WatkinsWC, KrakowiakPA, et al. (1997) Mutations in human TBX3 alter limb, apocrine and genital development in ulnar-mammary syndrome. Nat Genet 16: 311–315.

24. MerscherS, FunkeB, EpsteinJA, HeyerJ, PuechA, et al. (2001) TBX1 is responsible for cardiovascular defects in velo-cardio-facial/DiGeorge syndrome. Cell 104: 619–629.

25. Nüsslein-VolhardC, WieschausE (1980) Mutations affecting segment number and polarity in Drosophila. Nature 287: 795–801.

26. QianL, LiuJ, BodmerR (2005) Neuromancer Tbx20-related genes (H15/midline) promote cell fate specification and morphogenesis of the Drosophila heart. Dev Biol 279: 509–524.

27. LiuQX, HiramotoM, UedaH, GojoboriT, HiromiY, et al. (2009) Midline governs axon pathfinding by coordinating expression of two major guidance systems. Genes Dev 23: 1165–1170.

28. BhatKM (2007) Wingless activity in the precursor cells specifies neuronal migratory behavior in the Drosophila nerve cord. Dev Biol 311: 613–622.

29. BossingT, BrandAH (2002) Dephrin, a transmembrane ephrin with a unique structure, prevents interneuronal axons from exiting the Drosophila embryonic CNS. Development 129: 4205–4218.

30. DavisS, GaleNW, AldrichTH, MaisonpierrePC, LhotakV, et al. (1994) Ligands for EPH-related receptor tyrosine kinases that require membrane attachment or clustering for activity. Science 266: 816–819.

31. HolderN, KleinR (1999) Eph receptors and ephrins: effectors of morphogenesis. Development 126: 2033–2044.

32. MellitzerG, XuQ, WilkinsonDG (2000) Control of cell behaviour by signalling through Eph receptors and ephrins. Curr Opin Neurobiol 10: 400–408.

33. WilkinsonDG (2001) Multiple roles of EPH receptors and ephrins in neural development. Nat Rev Neurosci 2: 155–164.

34. GaleNW, HollandSJ, ValenzuelaDM, FlennikenA, PanL, et al. (1996) Eph receptors and ligands comprise two major specificity subclasses and are reciprocally compartmentalized during embryogenesis. Neuron 17: 9–19.

35. DavyA, RobbinsSM (2000) Ephrin-A5 modulates cell adhesion and morphology in an integrin-dependent manner. EMBO J 19: 5396–5405.

Štítky
Genetika Reprodukčná medicína

Článok vyšiel v časopise

PLOS Genetics


2013 Číslo 12
Najčítanejšie tento týždeň
Najčítanejšie v tomto čísle
Kurzy

Zvýšte si kvalifikáciu online z pohodlia domova

Získaná hemofilie - Povědomí o nemoci a její diagnostika
nový kurz

Eozinofilní granulomatóza s polyangiitidou
Autori: doc. MUDr. Martina Doubková, Ph.D.

Všetky kurzy
Prihlásenie
Zabudnuté heslo

Zadajte e-mailovú adresu, s ktorou ste vytvárali účet. Budú Vám na ňu zasielané informácie k nastaveniu nového hesla.

Prihlásenie

Nemáte účet?  Registrujte sa

#ADS_BOTTOM_SCRIPTS#